Abstract Aortic valve stenosis (AS) is one of the most diffuse valvular diseases in developed countries. AS is a progressive disease, which usually results in serious life-threatening adverse events. Defining a treatment strategy for AS is a focus of cardiovascular research, although the topic is still controversial because of its related clinical and economical implications. Surgical aortic valve replacement (AVR),which is regarded as the gold standard for the treatment of severe symptomatic AS, affords excellent results, particularly in asymptomatic patients with good functional status. AVR requires the institution of cardiopulmonary bypass and aortic cross-clamping, and the duration of these procedures is directly associated with increasing morbidity and mortality, especially in patients with preoperative comorbidities. Accordingly, techniques aimed at decreasing the duration of cardiopulmonary bypass and aortic cross-clamping have the potential to improve postoperative outcomes of AVR. In the present study, we demonstrated that the Perceval sutureless bioprosthesis could significantly reduce the duration of the surgical procedure. This was associated with improved immediate postoperative outcomes and long-term freedom from adverse events. The use of a Perceval sutureless bioprosthesis can facilitate AVR through minimally invasive approaches and is associated with fewer transfusions of packed red cells compared to full sternotomy approaches, even with traditional stented bioprostheses. It could be expected that patients at intermediate-high risk would benefit more from the combination of a fast surgical procedure, performed with reduced surgical invasiveness. When compared to transcatheter aortic valve implantation (TAVI), the Perceval sutureless bioprosthesis was associated with increased incidence of device success as well as less paravalvular leak, with similar immediate and 1-year outcomes. Finally, AVR with the Perceval sutureless bioprosthesis provided excellent hemodynamics at rest and under high workload. The significant increase of effective orifice area under stress suggests that the Perceval sutureless bioprosthesis is the valve of choice for patients with small aortic annuli or when prosthesis-patient mismatch is anticipated. / Tiivistelmä Aorttaläpän ahtauma on yksi yleisimmistä läppävioista kehittyneissä maissa. Aorttaläpän ahtauma on etenevä sairaus, joka yleensä johtaa vakaviin henkeä uhkaaviin haittatapahtumiin. Aorttaläpän ahtauman hoitotavasta keskustellaan kiivaasti sydän- ja verisuonitautien tutkimuksessa siihen liittyvien kliinisten ja taloudellisten vaikutusten vuoksi. Aorttaläppäleikkausta, jossa aorttaläppä korvataan proteesilla, on aina pidetty vaikean oireisen aorttaläpän ahtauman hoidon kultaisena standardina, koska sen tulokset ovat erinomaisia, etenkin oireettomilla potilailla, joilla sydämen toiminta on hyvä. Leikkaus vaatii sydän-keuhkokoneen käyttöä ja aortan sulkemista, joiden kesto on suoraan yhteydessä kasvavaan sairastavuuteen ja kuolleisuuteen erityisesti potilailla, joilla on muitakin sairauksia. Niinpä tekniikat, jotka lyhentävät sydän-keuhkokoneen käyttöaikaa ja aortan sulkuaikaa, voivat mahdollisesti parantaa aorttaläppäleikkauksen tuloksia. Tässä tutkimuksessa osoitettiin, että ompeleettoman biologisen Perceval-läppäproteesin käyttö vähensi merkittävästi leikkauksen kestoa. Tämä oli yhteydessä parantuneisiin lyhyen ja pitkän aikavälin tuloksiin leikkauksen jälkeen. Ompeleettoman biologisen Perceval-läppäproteesin käyttö voi helpottaa aorttaläppäleikkausta, koska se voidaan asentaa vähemmän kajoavasta avauksesta, ja siihen liittyy vähemmän punasolusiirtoja rintalastan kokoavaukseen verrattuna, myös silloin kun käytetään kokoavausta ja perinteisiä stenttibioproteeseja. Voisi olla odotettavaa, että keskisuuren tai suuren riskin potilaat hyötyisivät enemmän leikkauksesta, jossa yhdistyvät toimenpiteen nopeus ja vähäisempi kajoavuus. Katetriteitse asennettuun biologiseen keinoläppään (TAVI) verrattuna ompeleeton biologinen Perceval-läppäproteesi oli yhteydessä parempaan laitteen toimimiseen ja pienempään paravalvulaariseen vuotoon. Muut tulokset heti leikkauksen jälkeen ja yhden vuoden seurannassa olivat samanlaisia. Lopuksi voidaan todeta, että aorttaläppäleikkaukseen ompeleettomalla biologisella Perceval-läppäproteesilla liittyi erinomainen hemodynamiikka levossa ja korkean työkuorman aikana. Stressin aikaisen tehokkaan aorttaläpän aukon pinta-alan merkittävä kasvu osoittaa, että ompeleeton biologinen Perceval-läppäproteesi on hyvä valinta potilaille, joilla on pieni aorttaläpän aukko tai kun on odotettavissa proteesin ja potilaan yhteensopimattomuutta.

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13399号 / 論医博第2223号 / 新制||医||1051(附属図書館) / (主査)教授 今中 雄一, 教授 佐藤 俊哉, 教授 福田 和彦 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Transcatheter aortic valve replacement in the setting of failed surgical bioprosthesis (valve-in-valve) is a valuable option for patients with bioprosthetic aortic stenosis or regurgitation who are deemed high risk for repeat open heart surgery. Although the procedure is successful with proper preprocedural assessment, instances of left main (LM) coronary artery ostium obstruction have been documented. We present a case of LM coronary obstruction in the immediate postoperative period following implantation of a 20-mm Edwards Sapien 3 valve inside the degenerated 21-mm Mitroflow bioprosthesis stenosis, which was treated with double stenting alongside the Edwards Sapien 3 valve creating a channel (“neo left main”) that extended from mid-LM to the upper margin of the Edwards Sapien 3 valve. Although valve-in-valve in a Mitroflow degenerated bioprosthesis is a relatively safe procedure, 2 or more stents may be necessary to scaffold a channel to the coronary arteries between Edwards Sapien 3 prosthesis and aorta in the event of a coronary obstruction.

Objective: Studies have shown that iodinated radiocontrast use is associated with acute renal failure especially in the presence of chronic kidney disease and multiple factors modulate this risk. The purpose of this meta-analysis is to compare the incidence of renal failure requiring hemodialysis between transfemoral (TF) and transapical (TA) transcatheter aortic valve replacement using the Edwards valve. Methods: The PubMed database was searched from January 2000 through December 2014. A total of 10 studies (n = 2,459) comparing TF (n = 1,268) and TA (n = 1,191) TAVR procedures using the Edwards valve were included. Variables of interest were baseline logistic EuroSCORE, prevalence of diabetes mellitus, hypertension, peripheral arterial disease, chronic kidney disease and amount of contrast used. The primary endpoint was incidence of renal failure requiring hemodialysis. The odds ratio and 95% CI were computed and P < 0.05 was considered as the level of significance. Results: The logistic EuroSCORE was significantly higher in TA compared to TF (P = 0.001) TAVR. The amount of contrast (mL) used was significantly higher in the TF group compared to the TA group (mean difference: 36.9, CI: 25.7-48.1, P < 0.001). The incidence of hemodialysis following the procedure was significantly higher in the TA group compared to TF group (odds ratio = 4.3, CI: 2.4-7.8, P < 0.00001). Conclusions: This meta-analysis suggests that despite the lower amount of contrast used in TA-TAVR, the incidence of renal failure requiring hemodialysis was higher with the Edwards valve. This suggests that the incidence of renal failure requiring hemodialysis after TAVR is associated with baseline comorbidities in the TA-TAVR group rather than the volume of contrast used.

Objectives: In patients with severe aortic stenosis who are at high risk for surgery, transcatheter aortic valve replacement (TAVR) has emerged as an alternative procedure using EV or CV. The objective of this meta-analysis is to compare 1-year mortality and major adverse cardiovascular and cerebrovascular events (MACCE) between Edwards valve (EV) and Medtronic CoreValve (CV). Methods: PubMed and the Cochrane Center Register of Controlled Trials were searched through December 2014. Twenty seven studies (n = 12,249) comparing TAVR procedure that used EV (n = 5745) and CV (n = 6504) were included. End points were procedural success rates, post-procedural mortality, myocardial infarction (MI), stroke, major bleeding, major vascular complications, incidence of new permanent pacemaker (PPM) placement and new left bundle branch block (LBBB). The odds ratio (OR) with 95% confidence interval (CI) was computed and p < 0.05 was considered for significance. Results: There were no significant differences between EV and CV for post-procedural in-hospital, 30-day and 1-year all-cause mortality rates (p = 0.53, 0.33 and 0.94 respectively), cardiovascular mortality (p = 0.61), stroke (p = 0.54), major bleeding (p = 0.25) and major vascular complications (p = 0.27). MI was significantly lower with EV compared to CV (OR: 0.56, CI: 0.35-0.89, p = 0.01). Placement of new PPM and new onset LBBB were significantly higher in CV compared to EV (OR: 3.35, CI: 2.96-3.79, p < 0.00001 and OR: 6.55, CI: 4.76-9.03, p < 0.00001 respectively). Conclusions: The results of our meta-analysis suggest that TAVR procedure using CV may be associated with a higher incidence of MI, new PPM placement, and new onset LBBB compared to EV. However, the type of valve placed does not affect mortality.

No description available.

Ischemia caused by particles becoming dislodged during transcatheter aortic valve replacement (TAVR) is a possible complication of TAVR. The particles that become dislodged can travel out of the aortic valve, into the aortic arch, and then into either the brachiocephalic artery, the left common carotid artery, the left subclavian artery or continue into the descending aorta. If the particles continue into the descending aorta it poses no risk of causing ischemia however if it travels into the other arteries then it increases the possibility of the particle causing an ischemic event. The goal of this study is to determine what parameters cause the particle to enter one artery over another. The parameters analyzed are the particle diameter, the particle density, the blood pressure, and the diameter of the catheter used in the surgery. This was done by creating a finite element model in COMSOL Multiphysics® to track the particles flowing through a scan of an actual aortic arch. It was determined that the particle diameter, particle density, and the blood pressure affect which artery the particles take to exit the aortic arch. However the diameter of the surgical catheter used in a transaortic approach is not statistically significant when determining which artery the particles will exit. The study shows that larger diameter particle would lead to a higher transmissions probability into the brachiocephalic artery, the left common carotid artery, and the left subclavian artery while a smaller diameter particle would have a higher transmission probability for the descending aorta. Averaging all particle diameters, densities and blood pressure found that 54.95 ± 13.66% of the particles released will travel into the cerebral circulatory system.

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.

Background:  The right ventricle (RV) is multi-compartmental in orientation with a complex structural geometry. However, assessment of this part of the heart has remained an elusive clinical challenge. As a matter of fact, its importance has been underestimated in the past, especially its role as a determinant of cardiac symptoms, exercise capacity in chronic heart failure and survival in patients with valvular disease of the left heart. Evidence also exists that pulmonary hypertension (PH) affects primarily the right ventricular function. On the other hand, previous literature suggested that severe aortic stenosis (AS) affects left ventricular (LV) structure and function which partially recover after aortic valve replacement (AVR). However, the impact of that on RV global and segmental function remains undetermined.  Objectives: We sought to gain more insight into the RV physiology using 3D technology, Speckle tracking as well as already applicable echocardiographic measures. Our first aim was to assess the normal differential function of the RV inflow tract (IT), apical and outflow tract (OT) compartments, also their interrelations and the response to pulmonary hypertension. We also investigated the extent of RV dysfunction in severe AS and its response to AVR. Lastly, we studied the extent of global and regional right ventricular dysfunction in patients with pulmonary hypertension of different aetiologies and normal LV function. Methods: The studies were performed on three different groups; (1) left sided heart failure with (Group 1) and without (Group 2) secondary pulmonary hypertension, (2) severe aortic stenosis and six months post AVR and (3) pulmonary hypertension of different aetiologies and normal left ventricular function. We used 3D, speckle tracking echocardiography and conventionally available Doppler echocardiographic transthoracic techniques including M-mode, 2D and myocardial tissue Doppler. All patients’ measurements were compared with healthy subjects (controls). Statistics were performed using a commercially available SPSS software. Results: 1-  Our RV 3D tripartite model was validated with 2D measures and eventually showed strong correlations between RV inflow diameter (2D) and end diastolic volume (3D) (r=0.69, p&lt;0.001) and between tricuspid annular systolic excursion (TAPSE) and RV ejection fraction (3D) (r=0.71, p&lt;0.001). In patients (group 1 &amp; 2) we found that the apical ejection fraction (EF) was less than the inflow and outflow (controls:  p&lt;0.01 &amp; p&lt;0.01, Group 1:  p&lt;0.05 &amp; p&lt;0.01 and Group 2: p&lt;0.05 &amp; p&lt;0.01, respectively). Ejection fraction (EF) was reduced in both patient groups (p&lt;0.05 for all compartments). Whilst in controls, the inflow compartment reached the minimum volume 20 ms before the outflow and apex, in Group 2 it was virtually simultaneous. Both patient groups showed prolonged isovolumic contraction (IVC) and relaxation (IVR) times (p&lt;0.05 for all). Also, in controls, the outflow tract was the only compartment where the rate of volume fall correlated with the time to peak RV ejection (r = 0.62, p = 0.03). In Group 1, this relationship was lost and became with the inflow compartment (r = 0.61, p = 0.01). In Group 2, the highest correlation was with the apex (r=0.60, p&lt;0.05), but not with the outflow tract. 2- In patients with severe aortic stenosis, time to peak RV ejection correlated with the basal cavity segment (r = 0.72, p&lt;0.001) but not with the RVOT. The same pattern of disturbance remained after 6 months of AVR (r = 0.71, p&lt;0.001). In contrast to the pre-operative and post-operative patients, time to RV peak ejection correlated with the time to peak outflow tract strain rate (r = 0.7, p&lt;0.001), but not with basal cavity function. Finally in patients, RVOT strain rate (SR) did not change after AVR but basal cavity SR fell  (p=0.04). 3- In patients with pulmonary hypertension of different aetiologies and normal LV function, RV inflow and outflow tracts were dilated (p&lt;0.001 for both). Furthermore, TAPSE (p&lt;0.001), inflow velocities (p&lt;0.001), basal and mid-cavity strain rate (SR) and longitudinal displacement (p&lt;0.001 for all) were all reduced. The time to peak systolic SR at basal, mid-cavity (p&lt;0.001 for both) and RVOT (p=0.007) was short as was that to peak displacement (p&lt;0.001 for all). The time to peak pulmonary ejection correlated with time to peak SR at RVOT (r=0.7, p&lt;0.001) in controls, but with that of the mid cavity in patients (r=0.71, p&lt;0.001). Finally, pulmonary ejection acceleration (PAc) was faster (p=0.001) and RV filling time shorter in patients (p=0.03) with respect to controls. Conclusion: RV has distinct features for the inflow, apical and outflow tract compartments, with different extent of contribution to the overall systolic function. In PH, RV becomes one dyssynchronous compartment which itself may have perpetual effect on overall cardiac dysfunction. In addition, critical aortic stenosis results in RV configuration changes with the inflow tract, rather than outflow tract, determining peak ejection. This pattern of disturbance remains six month after valve replacement, which confirms that once RV physiology is disturbed it does not fully recover. The findings of this study suggest an organised RV remodelling which might explain the known limited exercise capacity in such patients. Furthermore, in patients with PH of different aetiologies and normal LV function, there is a similar pattern of RV disturbance. Therefore, we can conclude that early identification of such changes might help in identifying patients who need more aggressive therapy early on in the disease process.

Background: Aortic stenosis (AS) is the most common heart valve disease in Europe and North America. Age-related calcification of the valve is the commonest cause of acquired AS, especially in patients older than 70 years.Conventional surgical aortic valve replacement (SAVR) and the novel, minimally invasive transcatheter aortic valve implantation (TAVI), effectively preserve left ventricular (LV) function, relieve symptoms and improve survival in patients with severe symptomatic AS. However, patients with impaired LV function may carry significant operative risk, and long recovery time. In addition, such patients might have other comorbidities, and hence adding another challenge. Thus evaluation of ventricular function before and after AVR, as well as critical evaluation of TAVI patients should contribute to better clinical outcome. Methods: We studied LV function by conventional echocardiography before and after SAVR in the following groups; (I) 86 patients (aged 71±10 years) with severe AS and LV dysfunction; (II) 112 consecutive elderly AS patients (aged 77±2 years) and compared them with 72 younger patients (aged 60±1 years); (III)66 patients (age 70±2 years, 53 male) who underwent AVR for severe AS with concurrent LV dysfunction; (IV) 89 consecutive patients with symptomatic severeAS who underwent successful TAVI, 45 of whom received trans-apical TAVI (TA)(age 80.8±4.9 year, 26 male) and 44 trans-femoral TAVI (TF) (age 82.9±5.8 year,22 male).The conventional echocardiographic measurements were made according to the guidelines. Severe AS was identified by aortic valve mean pressure gradient &gt;40mmHg or valve area &lt;1.0 cm2. LV systolic dysfunction was identified as ejection fraction (EF) &lt;50%. LV long-axis function was presented by mitral annular plane systolic excursion ( MAPSE ) at lateral wall and septal wall, which were measured from apical four-chamber view. Also from the same view, LV septal and lateral wall deformation using STE as well as global longitudinal systolic strain. The LV systolic twist as the net difference between apical rotation and basal rotation was measured from the parasternal apical and basal short-axis views in the TAVI patients. Results: Study I: In the low flow and high gradient group, operative (30-day) mortality was 10%, and peri-operative mortality was associated with lower mean LVEF, higher mitral E:A ratio, peak systolic pulmonary artery pressure (PSPAP), and higher serum creatinine (all p&lt;0.001), NYHA class III–IV, concomitant coronary artery bypass graft (CABG), urgent surgery, and longer bypass-time (all p&lt; 0.05). Mortality at 4 years was 17%. Univariate predictors of 4-year mortality were: lower EF (p&lt;0.001), presence of restrictive LV filling (p&lt;0.001), raised PSPAP (p&lt;0.001) and CABG (p=0.037). However, only EF&lt;40 % (p=0.03), the presence of restrictive LV filling (p=0.033) and raised PSPAP (p&lt;0.01)independently predicted mortality in this group.Study II: Elderly patients had higher NYHA class, more frequent atrial fibrillation (AF), coronary artery disease (CAD), emergency operation and use of bioprosthetic valves. They also had shorter E-wave deceleration time (DT) and larger left atria (LA) (p&lt;0.05 for all). 30-day mortality was 12% vs 4 % (Log Rank x2=3.02, p=0.08) and long term mortality was 18% vs 7% (Log Rank x2=4.38,p=0.04) in the two groups, respectively. Age was not related to mortality after adjustment for other variables. Among all variables, anemia (OR 4.20, CI:1.02–6.86, p=0.04), cardiopulmonary bypass (CPB) time (OR 1.02, CI 1.01–1.04,p&lt;0.01), significant patient prosthesis mismatch (PPM) (OR 5.43, CI 1.04–18.40,p&lt;0.05) were associated with 30-day mortality in elderly patients. Their long-term mortality was related to CBP time (OR 1.02, CI 1.00–1.05, p=0.04),PPM (OR 4.64, CI 1.33–16.11, p=0.02) and raised LA pressure: DT (OR 0.94, CI0.84–0.99, p=0.03) and pulmonary artery systolic pressure (PASP) (OR 1.12, CI1.03–1.19, p&lt;0.001).STUDY III: Following SAVR peak aortic pressure gradient (AOPG) decreased and indexed valve area increased (64±3 to 19±1 mmHg and 0.30±0.01 to 0.89±0.03 cm2/m2, p&lt;0.001 for both). LVEF increased (from 45±1 to 54±2%;p&lt;0.001), LV end diastolic and end-systolic dimensions fell (LVEDD index: from 33±1 to 30±1 mm/m2; and LVESD index: from 27±1 to 20±1 mm/m2; (p&lt;0.01 forboth). LV diastolic dysfunction improved as evidenced by the fall in E/A ratio (from 2.6±0.2 to 1.9±0.4) and prolongation of total filling time; (from 29.2±0.6 to31.4±0.5 s/min, p=0.01 for both). Among all echocardiographic variables, LV dimensions (LVEDD index, OR 0.70, CI 0.52–0.97, p&lt;0.05; LVESD index, OR 0.57, CI 0.40–0.85, p=0.005) were the two independent predictors of post-operative LV functional recovery on multivariate analysis. A cut-off value ofpre-operative LVESD index&lt;=27.5 mm/m2 was 85% sensitive and 72% specific inpredicting intermediate-term recovery of LV function after AVR (AUC, 0.72, p=0.002). STUDY IV: Before TAVI, there was no difference between the two patient groups in gender, age, body surface area (BSA) and baseline LV function. However, left ventricular mass index (LVMi), left atrial volume index (LAVi) and tricuspid regurgitation pressure drop (TRPdrop) were increased in the TA group (p&lt;0.05).One week after TAVI, aortic pressure gradient (AOPG) markedly dropped in thetwo groups (both p&lt;0.001), LVEDD index and LVESD index fell but EF andmyocardial strain remained unchanged. Overall cavity twist reduced (p&lt;0.048).Significant LVESD index reduction was only seen in TF group (p=0.02) with a slight increase in LVEF (p=0.04). Lateral MAPSE increased only in the TF group(p=0.02). LV longitudinal systolic strain remained unchanged in TA patients while apical lateral strain increased in TF group. LV apical rotation fell in the two groups but basal rotation increased only in the TA patients (p=0.02). LAVi reduced in bothgroups and to a greater extent in TF TAVI (p=0.006), as did TRPdrop (p&lt;0.001). Conclusion: SAVR and TAVI are two effective treatments for severe AS patients.The severity of pre-operative systolic and diastolic LV dysfunction is the major predictor of mortality following SAVR for low-flow and high gradient AS.Peri-operative AVR survival is encouraging in the elderly. Long term mortality in the elderly is related to PPM, LV diastolic dysfunction and secondary pulmonary hypertension. LV functional recovery was evident in most patients with LV dysfunction after SAVR. A lower prevalence of LV functional recovery in patients with large pre-operative LVESD index might signify the loss of contractile reserveand thus predict post-operative functional recovery. TAVI results in significant early improvement of segmental and overall ventricular function, particularly in patients receiving the trans-femoral approach. The delayed recovery of the trans-apical TAVI group, we studied, might reflect worse pre-procedural diastolic cavity function.