In-vitro analysis of normal and aneurismal human ascending aortic tissues using FT-IR microspectroscopy

FTIR microspectroscopy has shown to be a proven tool in the investigation of many tissue types. We have used this spectroscopic approach to analyse structural differences between normal and aneurismal aortic tissues and also aortas from patients with congenital anomalies like aortic bicuspid valves. Spectral analysis showed important variations in amide I and II regions, related to changes in alpha-helix and beta-sheet secondary structure of proteins that seem to be correlated to structural modifications of collagen and elastin. These proteins are the major constituents of the aortic wall associated to smooth muscular cells. The amide regions have thus been identified as a marker of structural modifications related to these proteins whose modifications can be associated to a given aortic pathological situation. Both univariate (total absorbance image and band ratio) and multivariate (principal components analysis) analyses of the spectral information contained in the infrared images have been performed. Differences between tissues have been identified by these two approaches and allowed to separate each group of aortic tissues. However, with univariate band ratio analysis, the pathological group was found to be composed of samples from aneurismal aortas associated or not with an aortic bicuspid valve. In contrast, PCA was able to separate these two types of aortic pathologies. For other groups, PCA and band ratio analysis can differentiate between normal, aneurismal, and none dilated aortas from patients with a bicuspid aortic valve.     

FTIR protein secondary structure analysis of human ascending aortic tissues

The advent of moderate dilatations in ascending aortas is often accompanied by structural modifications of the main components of the aortic tissue, elastin and collagen. In this study, we have undertaken an approach based on FTIR microscopy coupled to a curve‐fitting procedure to analyze secondary structure modifications in these proteins in human normal and pathological aortic tissues. We found that the outcome of the aortic pathology is strongly influenced by these proteins, which are abundant in the media of the aortic wall, and that the advent of an aortic dilatation is generally accompanied by a decrease of parallel β‐sheet structures. Elastin, essentially composed of β‐sheet structures, seems to be directly related to these changes and therefore indicative of the elastic alteration of the aortic wall. Conventional microscopy and confocal fluorescence microscopy were used to compare FTIR microscopy results with the organization of the elastic fibers present in the tissues. This in‐vitro study on 6 patients (three normal and three pathologic), suggests that such a spectroscopic marker, specific to aneurismal tissue characterization, could be important information for surgeons who face the dilemma of moderate aortic tissue dilatation of the ascending aortas. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Analysis of structural changes in normal and aneurismal human aortic tissues using FTIR microscopy

Aortic aneurisms are frequently asymptomatic but can induce dramatic complications. The diagnosis is only based on the aortic diameter and not on a structural and compositional basis. In this preliminary study, we propose infrared microspectroscopy to nondestructively probe normal and aneurismal human aortas. Spectra from 19 human ascending aortic biopsies (10 normal and 9 aneurismal) were acquired using infrared microspectroscopy. A 1500 x 150 microm(2) area of each 7-microm thick cryosection was investigated using a 30-microm spatial resolution with a total of about 200 spectra per sample. Spectral differences between normal and aneurismal tissues were mainly located in spectral regions related to proteins, such as elastin and collagen, and proteoglycans (1750-1000 cm(-1)). Tissue heterogeneity and sample classification have been evaluated using hierarchical cluster analysis of individual or mean spectra and their second derivative. Using spectral range related to proteins, 100% of good classification was obtained whereas the proteoglycan spectral range was less discriminant. This in vitro study demonstrates the potential of such technique to differentiate between normal and aneurismal aortas using selected spectral ranges. Future investigations will be focused on these specific spectral regions to determine the role of elastin and collagen in the discrimination of normal and pathological aortas.     

Analysis of Extracellular Superoxide Dismutase and Akt in Ascending Aortic Aneurysm With Tricuspid or Bicuspid Aortic Valve

Ascending aortic aneurysm (AsAA) is a consequence of medial degeneration (MD), deriving from apoptotic loss of smooth muscle cells (SMC) and fragmentation of elastin and collagen fibers. Alterations of extracellular matrix structure and protein composition, typical of medial degeneration, can modulate intracellular pathways. In this study we examined the relevance of extracellular superoxide dismutase (SOD3) and Akt in AsAA pathogenesis, evaluating their tissue distribution and protein levels in ascending aortic tissues from controls (n=6), patients affected by AsAA associated to tricuspid aortic valve (TAV, n=9) or bicuspid aortic valve (BAV, n=9). The results showed a significant reduction of SOD3, phospho-Akt and Akt protein levels in AsAA tissues from patients with BAV, compared to controls, whereas the differences observed between controls and patients with TAV were not significant. The decreased levels of SOD3 and Akt in BAV aortic tissues are associated with decreased Erk1/Erk2 phosphorylation and MMP-9 levels increase. The authors suggest a role of decreased SOD3 protein levels in the progression of AsAA with BAV and a link between ECM modifications of aortic media layer and impaired Erk1/Erk2 and Akt signaling in the late stages of the aortopathy associated with BAV.Key words: Ascending aortic aneurysm, bicuspid aortic valve, medial degeneration, smooth muscle cells, extracellular superoxide dismutase, Akt, tri-cuspid aortic valve     

Systolic fluid–structure interaction model of the congenitally bicuspid aortic valve: assessment of modelling requirements

A transient fluid–structure interaction (FSI) model of a congenitally bicuspid aortic valve has been developed which allows simultaneous calculation of fluid flow and structural deformation. The valve is modelled during the systolic phase (the stage when blood pressure is elevated within the heart to pump blood to the body). The geometry was simplified to represent the bicuspid aortic valve in two dimensions. A congenital bicuspid valve is compared within the aortic root only and within the aortic arch. Symmetric and asymmetric cusps were simulated, along with differences in mechanical properties. A moving arbitrary Lagrange–Euler mesh was used to allow FSI. The FSI model requires blood flow to induce valve opening and induced strains in the region of 10%. It was determined that bicuspid aortic valve simulations required the inclusion of the ascending aorta and aortic arch. The flow patterns developed were sensitive to cusp asymmetry and differences in mechanical properties. Stiffening of the valve amplified peak velocities, and recirculation which developed in the ascending aorta. Model predictions demonstrate the need to take into account the category, including any existing cusp asymmetry, of a congenital bicuspid aortic valve when simulating its fluid flow and mechanics.     

Unraveling divergent gene expression profiles in bicuspid and tricuspid aortic valve patients with thoracic aortic dilatation: the ASAP study

Thoracic aortic aneurysm (TAA) is a common complication in patients with a bicuspid aortic valve (BAV), the most frequent congenital heart disorder. For unknown reasons TAA occurs at a younger age, with a higher frequency in BAV patients than in patients with a tricuspid aortic valve (TAV), resulting in an increased risk for aortic dissection and rupture. To investigate the increased TAA incidence in BAV patients, we obtained tissue biopsy samples from nondilated and dilated aortas of 131 BAV and TAV patients. Global gene expression profiles were analyzed from controls and from aortic intima-media and adventitia of patients (in total 345 samples). Of the genes found to be differentially expressed with dilation, only a few (<4%) were differentially expressed in both BAV and TAV patients. With the use of gene set enrichment analysis, the cell adhesion and extracellular region gene ontology sets were identified as common features of TAA in both BAV and TAV patients. Immune response genes were observed to be particularly overexpressed in the aortic media of dilated TAV samples. The divergent gene expression profiles indicate that there are fundamental differences in TAA etiology in BAV and TAV patients. Immune response activation solely in the aortic media of TAV patients suggests that inflammation is involved in TAA formation in TAV but not in BAV patients. Conversely, genes were identified that were only differentially expressed with dilation in BAV patients. The result has bearing on future clinical studies in which separate analysis of BAV and TAV patients is recommended.     

Fluid dynamics of aortic root dilation in Marfan syndrome

Aortic root dilation and propensity to dissection are typical manifestations of the Marfan Syndrome (MS), a genetic defect leading to the degeneration of the elastic fibres. Dilation affects the structure of the flow and, in turn, altered flow may play a role in vessel dilation, generation of aneurysms, and dissection. The aim of the present work is the investigation in-vitro of the fluid dynamic modifications occurring as a consequence of the morphological changes typically induced in the aortic root by MS. A mock-loop reproducing the left ventricle outflow tract and the aortic root was used to measure time resolved velocity maps on a longitudinal symmetry plane of the aortic root. Two dilated model aortas, designed to resemble morphological characteristics typically observed in MS patients, have been compared to a reference, healthy geometry. The aortic model was designed to quantitatively reproduce the change of aortic distensibility caused by MS. Results demonstrate that vorticity released from the valve leaflets, and possibly accumulating in the root, plays a fundamental role in redirecting the systolic jet issued from the aortic valve. The altered systolic flow also determines a different residual flow during the diastole.     

The Role of Rubella in the Etiology of Supravalvular Aortic Stenosis

The possibility of an etiological relationship between rubella embryopathy and sporadic forms of supravalvular aortic stenosis is considered. A case is presented of a patient with rubella embryopathy and supravalvular aortic stenosis associated with pulmonary valvular and peripheral pulmonary artery stenosis, bicuspid aortic valve, aortic valve stenosis and subendothelial myocardial fibrosis. A review of the literature revealed many clinical and pathological features common to both syndromes. The hypothesis that rubella virus produced germ-cell mutation and subsequent persistence of rubella in the zygote produced further fetal damage is presented to explain these observations.     

Compositional changes of the aortic valve similar to the artery with aging

To elucidate compositional changes of the cardiac valves with aging, the authors investigated the relationships among element contents in the aortic valves, in which the accumulation of calcium and phosphorus was the highest. The subjects consisted of 10 men and 14 women, ranging in age from 65 to 102 yr. Extremely significant direct correlations were found among the contents of calcium, phosphorus, magnesium, sodium, and zinc in the aortic valves. In contrast, significant inverse correlations were found between the contents of sulfur and the other elements, such as calcium, phosphorus, magnesium, and sodium. It should be noted that these correlations present in the aortic valves were very similar to those in the arteries, especially those in the thoracic aortas. The changes of the mass ratios of Mg/Ca and Mg/P in the aortic valves were similar to those in the thoracic aortas. As calcium and phosphorus increased in the aortic valve, the mass ratios Mg/Ca and Mg/P decreased reversely in the aortic valve. These results suggest that the compositional change of the aortic valve is very similar to that of the thoracic aorta.     

Structural modeling reveals microstructure-strength relationship for human ascending thoracic aorta

High lethality of aortic dissection necessitates accurate predictive metrics for dissection risk assessment. The not infrequent incidence of dissection at aortic diameters <5.5 cm, the current threshold guideline for surgical intervention (Nishimura et al., 2014), indicates an unmet need for improved evidence-based risk stratification metrics. Meeting this need requires a fundamental understanding of the structural mechanisms responsible for dissection evolution within the vessel wall. We present a structural model of the repeating lamellar structure of the aortic media comprised of elastic lamellae and collagen fiber networks, the primary load-bearing components of the vessel wall. This model was used to assess the role of these structural features in determining in-plane tissue strength, which governs dissection initiation from an intimal tear. Ascending aortic tissue specimens from three clinically-relevant patient populations were considered: non-aneurysmal aorta from patients with morphologically normal tricuspid aortic valve (CTRL), aneurysmal aorta from patients with tricuspid aortic valve (TAV), and aneurysmal aorta from patients with bicuspid aortic valve (BAV). Multiphoton imaging derived collagen fiber organization for each patient cohort was explicitly incorporated in our model. Model parameters were calibrated using experimentally-measured uniaxial tensile strength data in the circumferential direction for each cohort, while the model was validated by contrasting simulated tissue strength against experimentally-measured strength in the longitudinal direction. Orientation distribution, controlling the fraction of loaded collagen fibers at a given stretch, was identified as a key feature governing anisotropic tissue strength for all patient cohorts.     

A multiscale computational comparison of the bicuspid and tricuspid aortic valves in relation to calcific aortic stenosis

Patients with bicuspid aortic valve (BAV) are more likely to develop a calcific aortic stenosis (CAS), as well as a number of other ailments, as compared to their cohorts with normal tricuspid aortic valves (TAV). It is currently unknown whether the increase in risk of CAS is caused by the geometric differences between the tricuspid and bicuspid valves or whether the increase in risk is caused by the same underlying factors that produce the geometric difference. CAS progression is understood to be a multiscale process, mediated at the cell level. In this study, we employ multiscale finite-element simulations of the valves. We isolate the effect of one geometric factor, the number of cusps, in order to explore its effect on multiscale valve mechanics, particularly in relation to CAS. The BAV and TAV are modeled by a set of simulations describing the cell, tissue, and organ length scales. These simulations are linked across the length scales to create a coherent multiscale model. At each scale, the models are three-dimensional, dynamic, and incorporate accurate nonlinear constitutive models of the valve leaflet tissue. We compare results between the TAV and BAV at each length scale. At the cell-scale, our region of interest is the location where calcification develops, near the aortic-facing surface of the leaflet. Our simulations show the observed differences between the tricuspid and bicuspid valves at the organ scale: the bicuspid valve shows greater flexure in the solid phase and stronger jet formation in the fluid phase relative to the tricuspid. At the cell-scale, however, we show that the region of interest is shielded against strain by the wrinkling of the fibrosa. Thus, the cellular deformations are not significantly different between the TAV and BAV in the calcification-prone region. This result supports the assertion that the difference in calcification observed in the BAV versus TAV may be due primarily to factors other than the simple geometric difference between the two valves.     

Coronary artery anomalies and aortic valve morphology in the Syrian hamster

In the Syrian hamster, anomalies in the origin of the left coronary artery are significantly associated with the bicuspid condition of the aortic valve. In this species, bicuspid aortic valves are expressions of a trait, the variation of which takes the form of a phenotypic continuum, ranging from a tricuspid aortic valve with no commissural fusion to a bicuspid aortic valve with the aortic sinuses located in ventrodorsal orientation and devoid of any raphe. The intermediate stages of the continuum are represented by tricuspid aortic valves with a more or less extensive fusion of the ventral commissure and bicuspid aortic valves with a more or less developed raphe located in the ventral aortic sinus. The present study was designed to decide whether there is a gap between tricuspid and bicuspid aortic valves regarding the incidence of coronary artery anomalies, or whether this incidence varies according to the different tricuspid and bicuspid morphotypes of the continuum. The study was carried out in Syrian hamsters belonging to a single inbred family with a high incidence of tricuspid aortic valves with fusion of the ventral commissure, bicuspid aortic valves, and anomalies in the origin of the left coronary artery, i.e. single right coronary artery ostium in aorta, anomalous origin of the left coronary artery from the pulmonary artery, and anomalous origin of the left coronary artery from the dorsal aortic sinus. The specimens were examined by means of a stereomicroscope and, in several cases, scanning electron microscopy was also used. The relationships between anomalous coronary artery patterns and aortic valve morphologies were tested using a logistic regression model. The results obtained indicate that there is no discontinuity between tricuspid and bicuspid aortic valves regarding the incidence of coronary artery anomalies. The probability of occurrence of anomalous coronary artery patterns increases continuously according to the deviation degree of the aortic valve from its normal (tricuspid) design. The present findings suggest that in the Syrian hamster, the morphogenetic mechanisms involved in the formation of congenital anomalous aortic valves and anomalies in the origin of the left coronary artery, respectively, are strongly related from an aetiological viewpoint.     

The extent of the raphe in bicuspid aortic valves is associated with aortic regurgitation and aortic root dilatation

Background

The clinical course of bicuspid aortic valves (BAVs) is variable. Data on predictors of aortopathy and valvular dysfunction mainly focus on valve morphology.

Aim

To determine whether the presence and extent of the raphe (fusion site of valve leaflets) is associated with the degree of aortopathy and valvular dysfunction in patients with isolated BAV and associated aortic coarctation (CoA).

Methods

Valve morphology and aortic dimensions of 255 BAV patients were evaluated retrospectively by echocardiography.

Results

BAVs with a complete raphe had a significantly higher prevalence of valve dysfunction (especially aortic regurgitation) than BAVs with incomplete raphes (82.9 vs. 66.7 %, p = 0.01). Type 1A BAVs (fusion of right and left coronary leaflets) and complete raphe had larger aortic sinus diameters compared with the rest of the population (37.74 vs. 36.01, p = 0.031). Patients with CoA and type 1A BAV had significantly less valve regurgitation (13.6 vs. 55.8 %, p < 0.001) and smaller diameters of the ascending aorta (33.7 vs. 37.8 mm, p < 0.001) and aortic arch (25.8 vs. 30.2 mm, p < 0.001) than patients with isolated BAV.

Conclusions

Type 1A BAV with complete raphe is associated with more aortic regurgitation and root dilatation. The majority of CoA patients have incomplete raphes, associated with smaller aortic root diameters and less valve regurgitation.     

Bicuspid aortic valve aortopathies: An hemodynamics characterization in dilated aortas

Bicuspid aortic valve (BAV) aortopathy remains of difficult clinical management due to its heterogeneity and further assessment of related aortic hemodynamics is necessary. The aim of this study was to assess systolic hemodynamic indexes and wall stresses in patients with diverse BAV phenotypes and dilated ascending aortas. The aortic geometry was reconstructed from patient-specific images while the aortic valve was generated based on patient-specific measurements. Physiologic material properties and boundary conditions were applied and fully coupled fluid-structure interaction (FSI) analysis were conducted. Our dilated aortic models were characterized by the presence of abnormal hemodynamics with elevated degrees of flow skewness and eccentricity, regardless of BAV morphotype. Retrograde flow was also present. Both features, predicted by flow angle and flow reversal ratios, were consistently higher than those reported for non-dilated aortas. Right-handed helical flow was present, as well as elevated wall shear stress (WSS) on the outer ascending aortic wall. Our results suggest that the abnormal flow associated with BAV may play a role in aortic enlargement and progress it further on already dilated aortas.     

Selection of Reference Genes for Quantitative Real Time PCR (qPCR) Assays in Tissue from Human Ascending Aorta

Dilatation of the ascending aorta (AAD) is a prevalent aortopathy that occurs frequently associated with bicuspid aortic valve (BAV), the most common human congenital cardiac malformation. The molecular mechanisms leading to AAD associated with BAV are still poorly understood. The search for differentially expressed genes in diseased tissue by quantitative real-time PCR (qPCR) is an invaluable tool to fill this gap. However, studies dedicated to identify reference genes necessary for normalization of mRNA expression in aortic tissue are scarce. In this report, we evaluate the qPCR expression of six candidate reference genes in tissue from the ascending aorta of 52 patients with a variety of clinical and demographic characteristics, normal and dilated aortas, and different morphologies of the aortic valve (normal aorta and normal valve n = 30; dilated aorta and normal valve n = 10; normal aorta and BAV n = 4; dilated aorta and BAV n = 8). The expression stability of the candidate reference genes was determined with three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The expression analyses showed that the most stable genes for the three algorithms employed were CDKN1β, POLR2A and CASC3, independently of the structure of the aorta and the valve morphology. In conclusion, we propose the use of these three genes as reference genes for mRNA expression analysis in human ascending aorta. However, we suggest searching for specific reference genes when conducting qPCR experiments with new cohort of samples.     

Techniques of aortic valve repair

Similar to mitral repair, newer methods of aortic valve reconstruction are achieving excellent outcomes with an 85% to 90% freedom from valve-related complications at 10 years. The goal of this review is to illustrate these newer and more stable techniques of aortic valve repair. Most patients with aortic insufficiency from either trileaflet or bicuspid aortic valves are candidates for repair, in addition to selected patients with mixed aortic stenosis/insufficiency and aortic root aneurysms. Initially, aggressive commissural annuloplasty is performed to reduce measured valve diameter to 19 to 21 mm. Leaflet prolapse is corrected with plication stitches placed in the free edge of each leaflet adjacent to the Nodulus Arantius. In this regard, the leaflet free edge functions as the chorda tendinea of the aortic valve, and shortening with plication stitches raises the leaflet to a proper "effective height." Leaflet defects are augmented with gluteraldehyde-fixed autologous pericardium, and mild-to-moderate strategically placed spicules of calcium are removed with the cavitron ultrasonic surgical aspirator. Using these methods, most insufficient aortic valves, and many with mixed lesions, can be satisfactorily repaired. Six cases are illustrated in this review, spanning the spectrum of pathologies from annular dilatation without leaflet defects, to standard congenital bicuspid valve with prolapse, to trileaflet prolapse, to unusual bicuspid pathology with calcification, to a moderately calcified trileaflet valve with mixed lesions, and to aortic root aneurysms with severe aortic insufficiency. All valves were repaired using the techniques described above with trivial residual leak and minimal gradients. All repairs have been followed with yearly echocardiography, and valve reconstruction with these methods is now quite stable with excellent late outcomes. Most insufficient aortic valves now can undergo stable repair with minimal late valve-related complications. Greater application of aortic valve repair seems indicated.     

Compositional and structural alterations of chondroitin and dermatan sulfates during the progression of atherosclerosis and aneurysmal dilatation of the human abdominal aorta

Glycosaminoglycans participate in several biological functions in the arterial wall through their specific structures. They undergo specific compositional and structural modifications during the development of vascular diseases. The present study was performed to determine the variations in the concentration and the structural characteristics of galactosaminoglycans--chondroitin sulfate (CS) and dermatan sulfate (DS)--during the progression of atherosclerosis and aneurysmal dilatation of the human abdominal aorta. The concentration of CS was increased 24% (p < or = 0.05) in atherosclerotic type II aortas, but it was significantly decreased (29%, p < or = 0.05) in atherosclerotic type V aortas and aneurysmal aortas (65%, p < or = 0.01). In contrast, the concentration of DS was almost constant in all stages of arterial disease examined. Significant structural alterations were detected in the disaccharide composition of galactosaminoglycans. The ratio of 6-sulfated to 4-sulfated disaccharides was increased in atherosclerotic type II aortas (4.0 instead of 3.1 in normal aortas) due to the marked increase of CS in this tissue. This ratio was significantly decreased in atherosclerotic type V and aneurysmal aortas (2.1 and 1.6, respectively) due to the significant reduction of CS in the respective tissues. In addition, significant decrease of the oversulfated disaccharides, which are mainly located in DS chains, was recorded in atherosclerotic and aneurysmal aortas. Particularly, deltadi-di(2,6)S were decreased 32% (p < or = 0.01) and 86% (p < or = 0.01) in atherosclerotic type II and V aortas and 88% (p < or = 0.01) in aneurysm. Deltadi-di(2,4)S were increased in atherosclerotic type II aortas (21%, p < or = 0.01), but significantly decreased in atherosclerotic type V (33%, p < or = 0.01) and aneurysmal aortas (56%, p < or = 0.01). The amounts of deltadi-di(4,6)S were not markedly affected in the diseased tissues. These results suggest that the concentration of galactosaminoglycans is differentially affected during the progression of atherosclerosis. Furthermore, the development of vascular disease is associated with specific structural modifications, especially with the significant reduction of particular types of oversulfated disaccharides, which may play essential biological roles in the arterial wall.     

Normal and abnormal development of the aortic wall and valve: correlation with clinical entities

Dilation of the wall of the thoracic aorta can be found in patients with a tricuspid (TAV) as well as a bicuspid aortic valve (BAV) with and without a syndromic component. BAV is the most common congenital cardiovascular malformation, with a population prevalence of 0.5–2 %. The clinical course is often characterised by aneurysm formation and in some cases dissection. The non-dilated aortic wall is less well differentiated in all BAV as compared with TAV, thereby conferring inherent developmental susceptibility. Furthermore, a turbulent flow, caused by the inappropriate opening of the bicuspid valve, could accelerate the degenerative process in the aortic wall. However, not all patients with bicuspidy develop clinical complications during their life. We postulate that the increased vulnerability for aortic complications in a subset of patients with BAV is caused by a defect in the early development of the aorta and aortic valve. This review discusses histological and molecular genetic aspects of the normal and abnormal development of the aortic wall and semilunar valves. Aortopathy associated with BAV could be the result of a shared developmental defect during embryogenesis.     

Does clinical data quality affect fluid-structure interaction simulations of patient-specific stenotic aortic valve models?

Numerical models are increasingly used in the cardiovascular field to reproduce, study and improve devices and clinical treatments. The recent literature involves a number of patient-specific models replicating the transcatheter aortic valve implantation procedure, a minimally invasive treatment for high-risk patients with aortic diseases. The representation of the actual patient’s condition with truthful anatomy, materials and working conditions is the first step toward the simulation of the clinical procedure.The aim of this work is to quantify how the quality of routine clinical data, from which the patient-specific models are built, affects the outputs of the numerical models representing the pathological condition of stenotic aortic valve.Seven fluid–structure interaction (FSI) simulations were performed, completed with a sensitivity analysis on patient-specific reconstructed geometries and boundary conditions. The structural parts of the models consisted of the aortic root, native tri-leaflets valve and calcifications. Ventricular and aortic pressure curves were applied to the fluid domain.The differences between clinical data and numerical results for the aortic valve area were less than 2% but reached 12% when boundary conditions and geometries were changed. The difference in the aortic stenosis jet velocity between measured and simulated values was less than 11% reaching 27% when the geometry was changed. The CT slice thickness was found to be the most sensitive parameter on the presented FSI numerical model.In conclusion, the results showed that the segmentation and reconstruction phases need to be carefully performed to obtain a truthful patient-specific domain to be used in FSI analyses.