Background and Objectives: Mitral stenosis with extensive mitral annular calcification (MAC) remains surgically challenging in respect to clinical outcome. Prolonged surgery time with imminent ventricular rupture and systolic anterior motion can be considered as a complex of causal factors. The aim of our alternative hybrid approach was to reduce the risk of annual rupture and paravalvular leaks and to avoid obstruction of the outflow tract. A review of the current literature was also carried out. Materials and Methods: Six female patients (mean age 76 9 years) with severe mitral valve stenosis and severely calcified annulus underwent an open implantation of an Edwards Sapien 3 prosthesis on cardiopulmonary bypass. Our hybrid approach involved resection of the anterior mitral leaflet, placement of anchor sutures and the deployment of a balloon expanded prosthesis under visual control. Concomitant procedures were carried out in three patients. Results: The mean duration of cross-clamping was 95 31 min and cardiopulmonary bypass was 137 60 min. The perioperative TEE showed in three patients an inconspicuous, heart valve-typical gradient on all implanted prostheses and a clinically irrelevant paravalvular leakage occurred in the anterior annulus. In the left ventricular outflow tract, mild to moderately elevated gradients were recorded. No adverse cerebrovascular events and pacemaker implantations were observed. All but one patient survived to discharge. Survival at one year was 83.3%. Conclusions: This “off label” implantation of the Edwards Sapien 3 prosthesis may be considered as a suitable bail-out approach for patients at high-risk for mitral valve surgery or deemed inoperable due to extensive MAC.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23767号 / 医博第4813号 / 新制||医||1056(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 大鶴 繁, 教授 小西 靖彦, 教授 森田 智視 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Aortic stenosis (AS) is a critical valvular disease often treated by Transcatheter Aortic Valve Replacement (TAVR). This thesis introduces several novel approaches for improving the assessment and management of AS and the associated TAVR procedure. The research presents new indices for characterizing AS progression, including the False Positive Rate (FPR) method for detecting and quantifying calcification in contrast-enhanced computed tomography (CT) images. This method adapts dynamically to the variability in calcium density and offers precise estimates of calcific burden. Additionally, a Minimal Variation Geometry Invariant Parametric Reconstruction (MVGIPR) method was developed to reconstruct the full geometry of the aortic valve complex (AVC). This approach enhances the accuracy of geometric models from routine CT scans, providing detailed 3D models of the aortic valve, including patient-specific anatomical and pathological features. Moreover, the Virtual Transcatheter Aortic Valve Replacement (VTAVR) framework is introduced for TAVR optimization and intervention planning using developments from both previous techniques. This novel simulation-based system incorporates kinematic modeling within a patient-specific parametric geometry to predict device deployment outcomes, including complications such as paravalvular leakage, patient-prosthesis mismatch, and left bundle branch block. By simulating patient-specific device deployment, the VTAVR framework may potentially enhance pre-procedural planning, leading to better surgical outcomes and reduced risks in TAVR procedures. / Thesis / Doctor of Philosophy (PhD) / Aortic stenosis (AS) is a condition where the heart’s aortic valve becomes narrowed due to calcification, restricting blood flow and leading to severe health risks, especially in older adults. This research introduces new ways to measure the progression of this disease and predict complications from the commonly used treatment called Transcatheter Aortic Valve Replacement (TAVR). Using advanced computational models, the study develops personalized aortic valve shape and structure assessment frameworks using routine clinical computed tomography (CT) imaging. Moreover, we introduce a virtual interventional simulation framework that can predict how a patient’s valve may respond to TAVR. This "Virtual TAVR" system may help treating physicians to plan surgeries more accurately by simulating different approaches, allowing them to identify the best treatment strategy for each patient. By improving our ability to predict complications, the system ultimately aims to increase the success rate of these life-saving procedures.

INTRODUCAO: A comunicação interatrial tipo \"ostium secundum\" é um defeito cardíaco congênito caracterizado pela deficiência parcial ou total da lâmina da fossa oval, também chamada de septo primo. Corresponde a 10 a 12% do total de cardiopatias congênitas, sendo a mais frequente na idade adulta. Atualmente a oclusão percutânea é o método terapêutico de escolha em defeitos com características anatômicas favoráveis para o implante de próteses na maioria dos grandes centros mundiais. A ecocardiografia transesofágica bidimensional com mapeamento de fluxo em cores é considerada a ferramenta padrão-ouro para a avaliação anatômica e monitoração durante do procedimento, sendo crucial para a ótima seleção do dispositivo. Neste sentido, um balão medidor é introduzido e insuflado através do defeito de forma a ocluí-lo temporariamente. A medida da cintura que se visualiza no balão (diâmetro estirado) é utilizada como referência para a escolha do tamanho da prótese. Recentemente a ecocardiografia tridimensional transesofágica em tempo real tem sido utilizada neste tipo de intervenção percutânea. Neste estudo avaliamos o papel da mesma na ótima seleção do dispositivo levando-se em consideração as dimensões e a geometria do defeito e a espessura das bordas do septo interatrial. METODO: Estudo observacional, prospectivo, não randomizado, de único braço, de uma coorte de 33 pacientes adultos portadores de comunicação interatrial submetidos a fechamento percutâneo utilizando dispositivo de nitinol autocentrável (Cera ®, Lifetech Scientific, Shenzhen, China). Foram analisadas as medidas do maior e menor diâmetro do defeito, sua área e as medidas do diâmetro estirado com balão medidor obtidas por meio das duas modalidades ecocardiográficas. Os defeitos foram considerados como elípticos ou circulares segundo a sua geometria; as bordas ao redor da comunicação foram consideradas espessas (>2 mm) ou finas. O dispositivo selecionado foi igual ou ate 2 mm maior que o diâmetro estirado na ecocardiografia transesofágica bidimensional (padrão-ouro). Na tentativa de identificar uma variável que pudesse substituir o diâmetro estirado do balão para a ótima escolha do dispositivo uma série de correlações lineares foram realizadas. RESULTADOS: A idade e peso médio foram de 42,1 ± 14,9 anos e 66,0 ± 9,4kg, respectivamente; sendo 22 de sexo feminino. Não houve diferenças estatísticas entre os diâmetros maior e menor ou no diâmetro estirado dos defeitos determinados por ambas as modalidades ecocardiográficas. A correlação entre as medidas obtidas com ambos os métodos foi ótima (r > 0,90). O maior diâmetro do defeito, obtido à ecoardiografia transesofágica tridimensional, foi a variável com melhor correlação com o tamanho do dispositivo selecionado no grupo como um todo (r= 0,89) e, especialmente, nos subgrupos com geometria elíptica (r= 0,96) e com bordas espessas ao redor do defeito (r= 0,96). CONCLUSÃO: Neste estudo em adultos com comunicações interatriais tipo ostium secundum submetidos à oclusão percutânea com a prótese Cera ®, a ótima seleção do dispositivo pôde ser realizada utilizando-se apenas a maior medida do defeito obtida na ecocardiografia transesofágica tridimensional em tempo real, especialmente nos pacientes com defeitos elípticos e com bordas espessas. / INTRODUCTION: The ostium secundum atrial septal defect is a congenital heart disease characterized by partial or total deficiency of the fossa ovalis, also known as the septum primum. It corresponds to 10-12% of all congenital heart defects, being the most frequently found in adulthood. Currently, percutaneous closure is the therapeutic method of choice for defects with suitable anatomic features for device implantation in most centers in the world. Bi-dimensional transesophageal echocardiography with color flow mapping is considered the gold-standard tool for anatomic assessment and procedural monitoring, being crucial for optimal device selection. In this regard, a sizing balloon is introduced and inflated across the defect with temporary occlusion. The waist measurement seen on the balloon (stretched diameter) is used as a reference for selection of device size. Recently, real time three-dimensional transesophageal echocardiography has been utilized in this type of percutaneous intervention. In this study we assessed the role of this modality in optimal device selection taking into consideration the dimensions and the geometry of the defect and the thickness of the interatrial septum rims. METHODS: Observational, prospective, non-randomized, single-arm study of a cohort of 33 adults with atrial septal defects submitted to percutaneous closure using a self-centered nitinol device (Cera (TM), Lifetech Scientific, Shenzhen, China). The largest and the smallest diameter of the defect, its area and the measurements of the stretched diameter of the sizing balloon were assessed by both echocardiographic modalities. The defects were considered as elliptical or circular according to their geometry; the rims surrounding the defect were considered thick (> 2 mm) or thin. The selected device was equal to or 2 mm larger than the stretched diameter on bi-dimensional transesophageal echocardiography (gold-standard). In an attempt to identify a variable that could replace the stretched balloon diameter, a series of linear correlations were performed. RESULTS: The mean age and weight were 42.1 ± 14.9 years and 66.0 ± 9.4 kgs, respectively; being 22 of the female gender. There were no statistical differences between the largest and smallest diameters of the defects and the stretched diameters determined by both echocardiographic modalities. The correlation between the measurements obtained by both methods was excellent (r > 0.90). The largest defect diameter obtained by three-dimensional transesophageal echocardiography was the variable that showed the best correlation with the selected device size in the entire group (r= 0.89), especially in the subgroups with elliptical geometry (r= 0.96) and with thick rims surrounding the defect (r=0.96). CONCLUSIONS: In this study in adults with ostium secundum atrial septal defects submitted to percutaneous occlusion with the Cera (TM) device, optimal device selection could be performed using solely the largest diameter of the defect obtained by real time three-dimensional transesophageal echocardiography, especially in patients with elliptical defects and thick rims.

Novel biomaterials provide a spectrum of possibilities. They can be engineered in different forms to understand how they would perform as different bioprosthetic conduits. Bacterial cellulose membranes may be suitable candidates as prosthetic valve leaflets in valve replacement surgeries due to their functional properties (hemodynamics, resistant to thrombosis). Biomaterials used for most bioprosthetic heart valves are cut, trimmed and sutured. A major challenge for the bi-leaflet configuration is that the cutting and suturing of biopolymers fabricated as sheets into a cylindrical form increases failure risk due to greater number of suture points and irregular coaptation. The objective was to culture the bacterial cellulose membrane as a continuous cylindrical construct and evaluate its mechanical properties. Various design features of the fabrication process such as culturing media and the hollow carrier-mandrel characteristics were evaluated. A comparative study of how bacterial cellulose grows on different hollow carrier membranes was conducted and thin smooth surface silicone tubes fabricated in the lab were found to be most suitable. A bioreactor for culturing cylindrical bacterial cellulose tubes on the outer surface of the hollow carrier was designed and fabricated. The mechanical properties of the fabricated tubes, specifically, their tensile strength, flexure, suture retention and tear resistance were characterized. Mechanical characterization studies showed the cylindrical bacterial cellulose tubes to be anisotropic, with preferential properties in the longitudinal (axial) direction of the tube. Preliminary results show that cylindrical bacterial cellulose tubes can be a promising candidate for use in prosthetic valve conduits.

Le facteur Willebrand (VWF) est une proteine multimerique qui a une sensibilite unique aux forces de cisaillement et aux variations hemodynamiques du flux sanguin comme celles rencontrees lors d’utilisation de dispositifs cardiovasculaires tels qu’un remplacement valvulaire aortique transcatheter (TAVI) ou un assistance circulatoire mecanique a flux continu (ACM-FC). Des travaux anterieurs nous ont permis de mettre en evidence une secretion endotheliale declenchee par les modifications du flux liees a l’utilisation de ces dispositifs.Dans la première partie de la these, nous avons choisi d’etudier le role de la pulsatilite arterielle dans la reponse endotheliale a l’aide de plusieurs modeles animaux porcins d’ACM-FC pour isoler le role de la pulsatilite dans un environnement a forces de cisaillement elevees et constantes. Nous avons observe dans un modele dose-reponse la relation entre le niveau de pulsatilite et la multimerisation du VWF et dans un modele en cross-over le caractere dynamique du relargage endothelial en reponse a des variations aigues de pulsatilite.Ces resultats nous ont permis de conceptualiser dans la deuxième partie l'utilisation du VWF dans l’evaluation de la severite des fuites paravalvulaires (FPV) post-procedure TAVI. Deux cohortes de 183 et 201 patients ont permis de demontrer l’excellente capacite diagnostique de l’analyse multimerique du VWF avec une sensibilite, une specificite et une valeur predictive negative de respectivement 92.3%, 94.9%, et 98.7%. Le test de diagnostic rapide TO-ADP (temps d’occlusion a l’ADP) donnait des resultats equivalents pour un seuil > 180 sec.Enfin dans la troisième partie de la these nous avons concu le design d’un essai clinique permettant d’evaluer la valeur ajoutee de l’utilisation de ce test de diagnostic rapide TO-ADP en salle de catheterisme pour l’amelioration des resultats proceduraux et cliniques des procedures TAVI. / Willebrand factor (VWF) is a multimeric protein that has a unique sensitivity to shear forces and hemodynamic variations in blood flow such as those encountered when using cardiovascular devices such as transcatheter aortic valve replacement (TAVI) or continuous flow mechanical circulatory assistance (CF-CAM).

Introduction: Transcatheter aortic valve implantation (TAVI) is an established procedure to treat severe aortic stenosis (AS). This study investigates the impact of ischemic heart disease (IHD) on survival in patients undergoing TAVI. Aim: Five-year all-cause mortality stratified according to the presence or absence of IHD. Methods: Retrospective register study including all patients that underwent a TAVI-procedure 2009 to 2018. Patients were stratified according to the presence or absence of IHD. Our primary end-point was five-year all-cause mortality. Survival was analyzed using Kaplan-Meier curve. Data were acquired through the SWENTRY registry and patient files. Results: A total of 264 patients were included in the study, with 139 (52.7 %) patients in the IHD group vs 125 (47.3 %) patients in the non-IHD group. Mean follow-up time was 40 ±30 months. At baseline, there was a higher proportion of males, patients with hypertension, peripheral arterial disease, left ventricular ejection fraction <50 % and, a higher EuroSCORE I in the IHD-group. Transfemoral approach was most common in both groups. No differences were noted in respect to peri- and postoperative complications. Five-year all-cause mortality was 17/38 (44.7 %) vs 18/30 (60.0 %), p = 0,232, in the IHD and non-IHD group respectively. Non-adjusted cumulative five-year survival was not significantly different between the groups (Log-Rank, p = 0,056). Conclusions: In patients with severe AS undergoing TAVI, the five-year all-cause mortality was not statistically different between patients with or without IHD.

<p>Transcatheter Arterial Embolization (TAE) is a method in which a catheter is inserted into an artery under fluoroscopy guidance. By using material that creates a thrombus, inserted through the catheter, the artery can be occluded and the bleeding stopped.</p><p>Endoscopy is the treatment of choice in upper gastrointestinal (GI) bleeding, but 10% to 30% of patients rebleed and needs other treatment options. Post Partum Hemorrhage (PPH) may evolve rapidly and can become life threatening. Obstetrical treatment will manage most cases, but in some cases emergency surgery is needed and in the worst case hysterectomy.</p><p>The primary aim of this thesis was to evaluate the clinical usefulness, improve the TAE technique and compare the outcome of TAE with surgery used as “salvage therapy” in patients with upper GI bleeding. Evaluate TAE technique and the long-term effect on the menstrual cycle and fertility in severe PPH.</p><p>To evaluate the clinical usefulness 13 patients were treated with TAE after endoscopic treatment failure and 5 were treated for recurrent hemorrhage after emergency surgery. </p><p>The clinical outcome and mortality rate of 40 patients treated with TAE was compared with 51 patients treated with surgery of upper GI bleedings. </p><p>In 13 patients the ulcer was marked with placement of a metallic clip at endoscopy to be able to locate the exact site of the bleeding ulcer during the TAE procedure.</p><p>A retrospective study of 20 patients with severe PPH treated with bilateral TAE of the uterine artery was performed. </p><p>TAE was found to be effective and an alternative to emergency surgery for control of massive upper GI bleeding. The 30-day mortality was lower in the TAE group (3%) compared to the surgical group (14%). </p><p>By marking the bleeding ulcer at endoscopy using a metallic clip the site of bleeding could be identified on angiography without extravasation of contrast media.</p><p>No major impact on fertility or menstruation cycle was found in patients treated with TAE in PPH. TAE in PPH is safe and have no major long-term side effect. By using TAE in PPH hysterectomy can be avoided.</p>

Transcatheter Arterial Embolization (TAE) is a method in which a catheter is inserted into an artery under fluoroscopy guidance. By using material that creates a thrombus, inserted through the catheter, the artery can be occluded and the bleeding stopped. Endoscopy is the treatment of choice in upper gastrointestinal (GI) bleeding, but 10% to 30% of patients rebleed and needs other treatment options. Post Partum Hemorrhage (PPH) may evolve rapidly and can become life threatening. Obstetrical treatment will manage most cases, but in some cases emergency surgery is needed and in the worst case hysterectomy. The primary aim of this thesis was to evaluate the clinical usefulness, improve the TAE technique and compare the outcome of TAE with surgery used as “salvage therapy” in patients with upper GI bleeding. Evaluate TAE technique and the long-term effect on the menstrual cycle and fertility in severe PPH. To evaluate the clinical usefulness 13 patients were treated with TAE after endoscopic treatment failure and 5 were treated for recurrent hemorrhage after emergency surgery. The clinical outcome and mortality rate of 40 patients treated with TAE was compared with 51 patients treated with surgery of upper GI bleedings. In 13 patients the ulcer was marked with placement of a metallic clip at endoscopy to be able to locate the exact site of the bleeding ulcer during the TAE procedure. A retrospective study of 20 patients with severe PPH treated with bilateral TAE of the uterine artery was performed. TAE was found to be effective and an alternative to emergency surgery for control of massive upper GI bleeding. The 30-day mortality was lower in the TAE group (3%) compared to the surgical group (14%). By marking the bleeding ulcer at endoscopy using a metallic clip the site of bleeding could be identified on angiography without extravasation of contrast media. No major impact on fertility or menstruation cycle was found in patients treated with TAE in PPH. TAE in PPH is safe and have no major long-term side effect. By using TAE in PPH hysterectomy can be avoided.

Hepatocellular carcinoma (HCC) is the second most common cancer in Taiwan and transcatheter arterial chemoembolization (TACE) is now the mainstay of treatment for noncurative HCC. Due to increasing medical costs yearly and financial problem of the Bureau of National Health Insurance, it is important to reduce medical resource utilization including hospital stay and medical costs. The aim is to figure out the risk factors of extended hospital stay, and increased in-hospital medical costs in hepatocellular carcinoma patients receiving transcatheter arterial chemoembolization. The result of this study should be available for further improvement of medical care quality in the limited medical resource. From January 2008 to January 2010, 162 patients (121 male and 41 female) with histologically proven hepatocellular carcinoma underwent TACE only (131 pts) or TACE followed by catheter placement for hepatic artery infusion chemotherapy (HAIC) (31pts) at district teaching hospital. The extended hospital stay (EHS) and extended post-procedure stay (EPS) are defined as stay larger than their median values (11 & 7 days respectively). Clinical demographic, disease factors, tumor factors, procedure (TACE)-related factors and complications are used to identify the univariate factors related to EHS and EPS statistically. To find out predictors of EHS, EPS and increased in-hospital medical costs, multiple linear regression analyses are used. The risk factors for EPS are procedure-related, including complications and procedure methods ( TACE + HAIC related to TACE only) (R2=.367, p<.001), while those for EHS are complications, encephalopathy, procedure methods, Child-Pugh classification C (related to classification A) and age (R2=.490, p<.001). The predictors for increased in-hospital medical costs include procedure methods, AJCC stage IV, T4 stage, hepatoencephalopathy and complications (R2=0.615, p<.001). Taking total hospital stay into consideration, the most important risk factor related to increased medical cost is total hosptial stay itself. The most powerful risk factor for EPS, EHS is procedure-related complication. The different procedure methods also affect hospital stay and medical costs. In order to reduce medical resource utilization, we should avoid post-procedure complication and pay attention to cirrhotic degree as well as American Joint Committee of Cancer (AJCC) tumor stage system. The result of this study can provide some ideas to adjust medical expense polices for the Bureau of National Health Insurance and to control medical cost for the hospitals.