Aortic pathologic conditions represent diverse disorders, including aortic aneurysm, acute aortic syndrome, traumatic aortic injury, and atherosclerosis. Given the nonspecific clinical features, noninvasive imaging is critical in screening, diagnosis, management, and posttherapeutic surveillance. Of the commonly used imaging modalities, including ultrasound, computed tomography, and MR imaging, the final choice often depends on a combination of factors: acuity of clinical presentation, suspected underlying diagnosis, and institutional practice. Further research is needed to identify the potential clinical role and define appropriate use criteria for advanced MR applications such as four-dimenional flow to manage patients with aortic pathologic conditions.

The opening and closing dynamics of the aortic valve (AV) has a strong influence on haemodynamics in the aortic root, and both play a pivotal role in maintaining normal physiological functions of the valve. The aim of this study was to establish a subject-specific fluid-structure interaction (FSI) workflow capable of simulating the motion of a tricuspid healthy valve and the surrounding haemodynamics under physiologically realistic conditions. A subject-specific aortic root was reconstructed from magnetic resonance (MR) images acquired from a healthy volunteer, whilst the valve leaflets were built using a parametric model fitted to the subject-specific aortic root geometry. The material behaviour of the leaflets was described using the isotropic hyperelastic Ogden model, and subject-specific boundary conditions were derived from 4D-flow MR imaging (4D-MRI). Strongly coupled FSI simulations were performed using a finite volume-based boundary conforming method implemented in FlowVision. Our FSI model was able to simulate the opening and closing of the AV throughout the entire cardiac cycle. Comparisons of simulation results with 4D-MRI showed a good agreement in key haemodynamic parameters, with stroke volume differing by 7.5% and the maximum jet velocity differing by less than 1%. Detailed analysis of wall shear stress (WSS) on the leaflets revealed much higher WSS on the ventricular side than the aortic side and different spatial patterns amongst the three leaflets.

Four-dimensional flow MRI is a powerful phase contrast technique used for assessing three-dimensional (3D) blood flow dynamics. By acquiring a time-resolved velocity field, it enables flexible retrospective analysis of blood flow that can include qualitative 3D visualization of complex flow patterns, comprehensive assessment of multiple vessels, reliable placement of analysis planes, and calculation of advanced hemodynamic parameters. This technique provides several advantages over routine two-dimensional flow imaging techniques, allowing it to become part of clinical practice at major academic medical centers. In this review, we present the current state-of-the-art cardiovascular, neurovascular, and abdominal applications.

Aortic pathologic conditions represent diverse disorders, including aortic aneurysm, acute aortic syndrome, traumatic aortic injury, and atherosclerosis. Given the nonspecific clinical features, noninvasive imaging is critical in screening, diagnosis, management, and posttherapeutic surveillance. Of the commonly used imaging modalities, including ultrasound, computed tomography, and MR imaging, the final choice often depends on a combination of factors: acuity of clinical presentation, suspected underlying diagnosis, and institutional practice. Further research is needed to identify the potential clinical role and define appropriate use criteria for advanced MR applications such as four-dimenional flow to manage patients with aortic pathologic conditions.

Bicuspid aortic valve (BAV), which affects 1% of the general population, results from the abnormal fusion of the cusps of the aortic valve. BAV can lead to the dilatation of the aorta, aortic coarctation, development of aortic stenosis (AS), and aortic regurgitation. Surgical intervention is usually recommended for patients with BAV and bicuspid aortopathy. This review aims to examine 4D-flow imaging as a tool in cardiac magnetic resonance imaging for assessing abnormal blood flow and its clinical application in BAV and AS. We present a historical clinical approach summarizing evidence of abnormal blood flow in aortic valve disease. We highlight how abnormal flow patterns can contribute to the development of aortic dilatation and novel flow-based biomarkers that can be used for a better understanding of the disease progression.

Cardiovascular magnetic resonance (CMR) has been utilized in the management and care of pediatric patients for nearly 40 years. It has evolved to become an invaluable tool in the assessment of the littlest of hearts for diagnosis, pre-interventional management and follow-up care. Although mentioned in a number of consensus and guidelines documents, an up-to-date, large, stand-alone guidance work for the use of CMR in pediatric congenital 36 and acquired 35 heart disease endorsed by numerous Societies involved in the care of these children is lacking. This guidelines document outlines the use of CMR in this patient population for a significant number of heart lesions in this age group and although admittedly, is not an exhaustive treatment, it does deal with an expansive list of many common clinical issues encountered in daily practice.

Cardiovascular magnetic resonance has been utilized in the management and care of pediatric patients for nearly 40 years. It has evolved to become an invaluable tool in the assessment of the littlest of hearts for diagnosis, pre-interventional management and follow-up care. Although mentioned in a number of consensus and guidelines documents, an up-to-date, large, stand-alone guidance work for the use of cardiovascular magnetic resonance in pediatric congenital 36 and acquired 35 heart disease endorsed by numerous Societies involved in the care of these children is lacking. This guidelines document outlines the use of cardiovascular magnetic resonance in this patient population for a significant number of heart lesions in this age group and although admittedly, is not an exhaustive treatment, it does deal with an expansive list of many common clinical issues encountered in daily practice.

Background Despite ongoing advances in surgical techniques for coarctation of the aorta (COA) repair, the long-term results are not always benign. Associated mixed valvular diseases (various combinations of aortic and mitral valvular pathologies) are responsible for considerable postoperative morbidity and mortality. We investigated the impact of COA and mixed valvular diseases on hemodynamics. Methods and Results We developed a patient-specific computational framework. Our results demonstrate that mixed valvular diseases interact with COA fluid dynamics and contribute to speed up the progression of the disease by amplifying the irregular flow patterns downstream of COA (local) and exacerbating the left ventricular function (global) (N=26). Velocity downstream of COA with aortic regurgitation alone was increased, and the situation got worse when COA and aortic regurgitation coexisted with mitral regurgitation (COA with normal valves: 5.27 m/s, COA with only aortic regurgitation: 8.8 m/s, COA with aortic and mitral regurgitation: 9.36 m/s; patient 2). Workload in these patients was increased because of the presence of aortic stenosis alone, aortic regurgitation alone, mitral regurgitation alone, and when they coexisted (COA with normal valves: 1.0617 J; COA with only aortic stenosis: 1.225 J; COA with only aortic regurgitation: 1.6512 J; COA with only mitral regurgitation: 1.3599 J; patient 1). Conclusions Not only the severity of COA, but also the presence and the severity of mixed valvular disease should be considered in the evaluation of risks in patients. The results suggest that more aggressive surgical approaches may be required, because regularly chosen current surgical techniques may not be optimal for such patients.

Coarctation of the aorta (CoA) typically requires repair, but re-interventions and vascular complications occur, particularly with associated defects like bicuspid aortic valve (BAV). Magnetic resonance imaging (MRI) may identify anatomic and hemodynamic factors contributing to clinical complications.

To investigate 4D flow MRI characteristics in pediatric CoA to determine parameters for long-term clinical surveillance.

Retrospective.

CoA (n = 21), CoA with BAV (n = 24), BAV alone (n = 29), and healthy control (n = 25).

A 1.5 T, 3D CE IR FLASH MRA, 4D flow MRI using 3D time resolved PC-MRI with velocity encoding.

Thoracic aorta diameters were measured from 3D CE-MRA. Peak systolic velocities and wall shear stress were calculated and flow patterns were visualized throughout the thoracic aorta using 4D flow. Repair characteristics, re-interventions, and need for anti-hypertensive medications were recorded.

Descriptive statistics, ANOVA with post hoc t-testing and Bonferroni correction, Kruskal-Wallis H, intraclass correlation coefficient, Fleiss' kappa.

Patients with CoA with or without repair had smaller transverse arch diameters compared to BAV alone and control cohorts (P < 0.05), higher peak systolic flow velocities and wall shear stress compared to controls in the transverse arch and descending aorta (P < 0.05), and flow derangements in the descending aorta. The most common CoA repairs were extended end-to-end anastomosis (n = 22/45, 48.9%, age at repair 1 ± 2 years, seven re-interventions) and stent/interposition graft placement (n = 10/45, 22.2%, age at repair 12 ± 3 years, one re-intervention). Anti-hypertensive medications were prescribed to 33.3% (n = 15/45) of CoA and 34.4% of BAV alone patients (n = 10/29).

Despite repair, CoA alters hemodynamics and flow patterns in the transverse arch and descending aorta. These findings may contribute to vascular remodeling and secondary complications. 4D flow MRI may be valuable in risk stratification, treatment selection and postintervention assessment. Long-term, prospective studies are warranted to correlate patient and MRI factors with clinical outcomes.

3 TECHNICAL EFFICACY: Stage 3.

Background: The population is aging and advances in multimodal imaging and transcatheter valve intervention have been prominent in the past two decades. This study investigated temporal trends in demographic characteristics, use of multimodal imaging, treatments, and outcomes in patients with bicuspid aortic valve (BAV). Methods and Results: A total of 1,497 patients (male 71.7%, 57 ± 14 years old) first diagnosed with BAV between January 2003 and December 2020, in a single tertiary center were divided into three groups according to year of diagnosis: group 1 (2003-2008, n = 269), group 2 (2009-2014, n = 594), and group 3 (2015-2020, n = 634). The patients' demographic characteristics, comorbidities, BAV morphology, BAV function, BAV-related disease, use of multimodal diagnostic imaging, treatment modality for BAV, and clinical outcomes were compared among the three groups. The ages at diagnosis and at the time of surgery/intervention increased considerably from group 1 to 3. The patients' comorbidity index also increased progressively. The proportion of non-dysfunctional BAV and significant AS increased, while that of significant AR decreased. The frequency of infective endocarditis as an initial presentation significantly decreased over time. Additionally, the use of multimodal imaging increased markedly in the most recent group. The results also indicated increasing trends in the use of bioprosthetic valves and transcatheter aortic valve replacement. Overall and cardiovascular survival rates improved from group 1 to 3 (log rank p < 0.001). Conclusions: For the past two decades, remarkable temporal changes have occurred in patient characteristics, use of multimodal diagnostic imaging, choice of treatment modality, and clinical outcomes in patients with BAV.

Introduction: Transcatheter aortic valve replacement (TAVR) is expanding to lower risk and younger patients with severe symptomatic aortic valve disease. Despite clinical and technological improvements, post-procedural aortic regurgitation (AR) remains a limitation of TAVR, particularly when compared to surgical aortic valve replacement. Although several methods for AR quantification after TAVR are currently available, its exact graduation in everyday clinical practice remains challenging.Areas covered: This review describes the currently available evaluation methods of AR after TAVR, with a special emphasis on the quantitative assessment using videodensitometric angiography, echocardiography and cardiac magnetic resonance imaging.Expert opinion: In the majority of clinical scenarios, satisfactory evaluation of post-TAVR AR can be achieved with a combination of post-procedural angiography, hemodynamic indices and transthoracic echocardiography. Nevertheless, some TAVR patients show 'intermediate' forms of post-procedural AR, in which quantitative evaluation is mandatory for prognostic purposes and further decision-making. Notably, interpretation of quantitative measures early post-TAVR is challenging because of the lack of left ventricular enlargement. Video-densitometric angiography is an emerging method that appears to be clinically attractive for immediate post-TAVR assessment, but requires further validation in everyday clinical practice.

Introduction: Dilatation of the proximal aorta is often associated with an aortic valve disease (e.g. bicuspid aortic valve, aortic stenosis), so-called 'valve-related aortopathy.' The definition of optimal timing for surgical intervention in valve-related aortopathy remains incompletely clarified. The limited value of traditional diameter-based intervention criteria has been recognized and more sophisticated diagnostic tools are necessary.Areas covered: This article aims to give an overview on the most recent literature addressing the different forms of valve-related aortopathies and the optimal timing of surgical intervention. It highlights the valve morphotype-dependent (BAV vs TAV) and the valve lesion-dependent aortopathies (stenosis vs regurgitation) and outlines the current treatment options of those pathologies. Further, this review discusses novel serological and rheological markers, potentially helping in the decision-making process in valve-related aortopathy. Systematic literature searches were performed using PubMed and Embase up to July 2019.Expert opinion: The combination of serological biomarkers and quantitative rheological markers for transvalvular flow eccentricity might be an additional useful tool. A possible solution for the future could be a risk score which considers body-surface-adjusted aortic diameters, activity of certain circulating biomarkers, transvalvular flow patterns, possible connective tissue disorders, and the valve morphology to define an individualized treatment strategy.

Bicuspid aortic valve disease is the most common congenital cardiac disorder, being present in 1% to 2% of the general population. Associated aortopathy is a common finding in patients with bicuspid aortic valve disease, with thoracic aortic dilation noted in approximately 40% of patients in referral centers. Several previous consensus statements and guidelines have addressed the management of bicuspid aortic valve-associated aortopathy, but none focused entirely on this disease process. The current guidelines cover all major aspects of bicuspid aortic valve aortopathy, including natural history, phenotypic expression, histology and molecular pathomechanisms, imaging, indications for surgery, surveillance, and follow-up, and recommendations for future research. It is intended to provide clinicians with a current and comprehensive review of bicuspid aortic valve aortopathy and to guide the daily management of these complex patients.

Bicuspid aortic valve (BAV) disease is the most common congenital cardiac malformation associated with an increased lifetime risk and a high rate of surgically-relevant valve deterioration and aortic dilatation. Genomic data revealed that different genes are associated with BAV. A dominant genetic factor for the recent past was the basis to the recommendation for a more extensive aortic intervention. However very recent evidence that hemodynamic stressors and alterations of wall shear stress play an important role independent from the genetic trait led to more conservative treatment recommendations. Therefore, there is a current need to improve the ability to risk stratify BAV patients in order to obtain an early detection of valvulopathy and aortopathy while also to predict valve dysfunction and/or aortic disease development. Imaging studies based on new cutting-edge technologies, such us 4-dimensional (4D) flow magnetic resonance imaging (MRI), two-dimensional (2D) or three-dimensional (3D) speckle-tracking imaging (STI) and computation fluid dynamics, combined with studies demonstrating new gene mutations, specific signal pathways alterations, hemodynamic influences, circulating biomarkers modifications, endothelial progenitor cell impairment and immune/inflammatory response, all detected BAV valvulopathy progression and aortic wall abnormality. Overall, the main purpose of this review article is to merge the evidences of imaging and basic science studies in a coherent hypothesis that underlies and thus projects the development of both BAV during embryogenesis and BAV-associated aortopathy and its complications in the adult life, with the final goal to identifying aneurysm formation/rupture susceptibility to improve diagnosis and management of patients with BAV-related aortopathy.

The bicuspid aortic valve (BAV) is a major risk factor for secondary aortopathy such as aortic dilation. The heterogeneous BAV morphotypes [left-right-coronary cusp fusion (LR), right-non-coronary cusp fusion (RN), and left-non-coronary cusp fusion (LN)] are associated with different dilation patterns, suggesting a role for hemodynamics in BAV aortopathogenesis. However, assessment of this theory is still hampered by the limited knowledge of the hemodynamic abnormalities generated by the distinct BAV morphotypes. The objective of this study was to compare experimentally the hemodynamics of a normal (i.e., non-dilated) ascending aorta (AA) subjected to tricuspid aortic valve (TAV), LR-BAV, RN-BAV, and NL-BAV flow. Tissue BAVs reconstructed from porcine TAVs were subjected to physiologic pulsatile flow conditions in a left-heart simulator featuring a realistic aortic root and compliant aorta. Phase-locked particle image velocimetry experiments were carried out to characterize the flow in the aortic root and in the tubular AA in terms of jet skewness and displacement, as well as mean velocity, viscous shear stress and Reynolds shear stress fields. While all three BAVs generated skewed and asymmetrical orifice jets (up to 1.7- and 4.0-fold increase in flow angle and displacement, respectively, relative to the TAV at the sinotubular junction), the RN-BAV jet was out of the plane of observation. The LR- and NL-BAV exhibited a 71% increase in peak-systolic orifice jet velocity relative to the TAV, suggesting an inherent degree of stenosis in BAVs. While these two BAV morphotypes subjected the convexity of the aortic wall to viscous shear stress overloads (1.7-fold increase in maximum peak-systolic viscous shear stress relative to the TAV-AA), the affected sites were morphotype-dependent (LR-BAV: proximal AA, NL-BAV: distal AA). Lastly, the LR- and NL-BAV generated high degrees of turbulence in the AA (up to 2.3-fold increase in peak-systolic Reynolds shear stress relative to the TAV) that were sustained from peak systole throughout the deceleration phase. This in vitro study reveals substantial flow abnormalities (increased jet skewness, asymmetry, jet velocity, turbulence, and shear stress overloads) in non-dilated BAV aortas, which differ from those observed in dilated aortas but still coincide with aortic wall regions prone to dilation.

Advancements in image-based computational modeling are producing increasingly more realistic representations of vasculature and hemodynamics, but so far have not compensated for cardiac motion when imposing inflow boundary conditions. The effect of cardiac motion on aortic flow is important when assessing sequelae in this region including coarctation of the aorta (CoA) or regurgitant fraction. The objective of this investigation was to develop a method to assess and correct for the influence of cardiac motion on blood flow measurements through the aortic valve (AoV) and to determine its impact on patient-specific local hemodynamics quantified by computational fluid dynamics (CFD). A motion-compensated inflow waveform was imposed into the CFD model of a patient with repaired CoA that accounted for the distance traveled by the basal plane during the cardiac cycle. Time-averaged wall shear stress (TAWSS) and turbulent kinetic energy (TKE) values were compared with CFD results of the same patient using the original waveform. Cardiac motion resulted in underestimation of flow during systole and overestimation during diastole. Influences of inflow waveforms on TAWSS were greatest along the outer wall of the ascending aorta (AscAo) (∼30 dyn/cm2). Differences in TAWSS were more pronounced than those from the model creation or mesh dependence aspects of CFD. TKE was slightly higher for the motion-compensated waveform throughout the aortic arch. These results suggest that accounting for cardiac motion when quantifying blood flow through the AoV can lead to different conclusions for hemodynamic indices, which may be important if these results are ultimately used to predict patient outcomes.

The correlation between bicuspid aortic valve (BAV) disease and aortopathy is not fully defined.

This study aimed to prospectively analyze the correlation between functional parameters of the aortic root and expression of aortopathy in patients undergoing surgery for BAV versus tricuspid aortic valve (TAV) stenosis.

From January 1, 2012 through December 31, 2014, 190 consecutive patients (63 ± 8 years, 67% male) underwent aortic valve replacement ± proximal aortic surgery for BAV stenosis (n = 137, BAV group) and TAV stenosis (n = 53, TAV group). All patients underwent pre-operative cardiac magnetic resonance imaging to evaluate morphological/functional parameters of the aortic root. Aortic tissue was sampled during surgery on the basis of the location of eccentric blood flow contact with the aortic wall, as determined by cardiac magnetic resonance (i.e., jet sample and control sample). Aortic wall lesions were graded using a histological sum score (0 to 21).

The largest cross-sectional aortic diameters were at the mid-ascending level in both groups and were larger in BAV patients (40.2 ± 7.2 mm vs. 36.6 ± 3.3 mm, respectively, p < 0.001). The histological sum score was 2.9 ± 1.4 in the BAV group versus 3.4 ± 2.6 in the TAV group (p = 0.4). The correlation was linear and comparable between the maximum indexed aortic diameter and the angle between the left ventricular outflow axis and aortic root (left ventricle/aorta angle) in both groups (BAV group: r = 0.6, p < 0.001 vs. TAV group r = 0.45, p = 0.03, z = 1.26, p = 0.2). Logistic regression identified the left ventricle/aorta angle as an indicator of indexed aortic diameter >22 mm/m(2) (odds ratio: 1.2; p < 0.001).

Comparable correlation patterns between functional aortic root parameters and expression of aortopathy are found in patients with BAV versus TAV stenosis.

The purpose of this study was to compare aortic flow and velocity quantification using 4D flow MRI and 2D CINE phase-contrast (PC)-MRI with either one-directional (2D-1dir) or three-directional (2D-3dir) velocity encoding. 15 healthy volunteers (51 ± 19 years) underwent MRI including (1) breath-holding 2D-1dir and (2) free breathing 2D-3dir PC-MRI in planes orthogonal to the ascending (AA) and descending (DA) aorta, as well as (3) free breathing 4D flow MRI with full thoracic aorta coverage. Flow quantification included the co-registration of the 2D PC acquisition planes with 4D flow MRI data, AA and DA segmentation, and calculation of AA and DA peak systolic velocity, peak flow and net flow volume for all sequences. Additionally, the 2D-3dir velocity taking into account the through-plane component only was used to obtain results analogous to a free breathing 2D-1dir acquisition. Good agreement was found between 4D flow and 2D-3dir peak velocity (differences = -3 to 6 %), peak flow (-7 %) and net volume (-14 to -9 %). In contrast, breath-holding 2D-1dir measurements exhibited indices significantly lower than free breathing 2D-3dir and 2D-1dir (differences = -35 to -7 %, p < 0.05). Finally, high correlations (r ≥ 0.97) were obtained for indices estimated with or without eddy current correction, with the lowest correlation observed for net volume. 4D flow and 2D-3dir aortic hemodynamic indices were in concordance. However, differences between respiration state and 2D-1dir and 2D-3dir measurements indicate that reference values should be established according to the PC-MRI sequence, especially for the widely used net flow (e.g. stroke volume in the AA).

The bicuspid aortic valve (BAV), which forms with two leaflets instead of three as in the normal tricuspid aortic valve (TAV), is associated with a spectrum of secondary valvulopathies and aortopathies potentially triggered by hemodynamic abnormalities. While studies have demonstrated an intrinsic degree of stenosis and the existence of a skewed orifice jet in the BAV, the impact of those abnormalities on BAV hemodynamic performance and energy loss has not been examined. This steady-flow study presents the comparative in vitro assessment of the flow field and energy loss in a TAV and type-I BAV under normal and simulated calcified states. Particle-image velocimetry (PIV) measurements were performed to quantify velocity, vorticity, viscous, and Reynolds shear stress fields in normal and simulated calcified porcine TAV and BAV models at six flow rates spanning the systolic phase. The BAV model was created by suturing the two coronary leaflets of a porcine TAV. Calcification was simulated via deposition of glue beads in the base of the leaflets. Valvular performance was characterized in terms of geometric orifice area (GOA), pressure drop, effective orifice area (EOA), energy loss (EL), and energy loss index (ELI). The BAV generated an elliptical orifice and a jet skewed toward the noncoronary leaflet. In contrast, the TAV featured a circular orifice and a jet aligned along the valve long axis. While the BAV exhibited an intrinsic degree of stenosis (18% increase in maximum jet velocity and 7% decrease in EOA relative to the TAV at the maximum flow rate), it generated only a 3% increase in EL and its average ELI (2.10 cm2/m2) remained above the clinical threshold characterizing severe aortic stenosis. The presence of simulated calcific lesions normalized the alignment of the BAV jet and resulted in the loss of jet axisymmetry in the TAV. It also amplified the degree of stenosis in the TAV and BAV, as indicated by the 342% and 404% increase in EL, 70% and 51% reduction in ELI and 48% and 51% decrease in EOA, respectively, relative to the nontreated valve models at the maximum flow rate. This study indicates the ability of the BAV to function as a TAV despite its intrinsic degree of stenosis and suggests the weak dependence of pressure drop on orifice area in calcified valves.

Aortic disease is routinely monitored with anatomic imaging, but until the recent advent of 3-directional phase contrast MRI (4D) flow, blood flow abnormalities have gone undetected. 4D flow measures aortic hemodynamic markers quickly. Qualitative flow visualization has spurred the investigation of new quantitative markers. Flow displacement and wall shear stress can quantify the effects of valve-related aortic flow abnormalities. Markers of turbulent and viscous energy loss approximate the increased energetic burden on the ventricle in disease states. This article discusses magnetic resonance flow imaging and highlights new flow-related markers in the context of aortic valve disease, valve-related aortic disease, and aortic wall disease.

Functional and molecular aortic imaging has shown great promise for evaluation of aortic disease, and may soon augment conventional assessment of aortic dimensions for the clinical management of patients.

A range of imaging techniques is available for evaluation of patients with aortic disease. Magnetic resonance blood flow imaging can identify atherosclerosis prone aortic regions and may be useful for predicting aneurysm growth. Computational modeling can demonstrate significant differences in wall stress between abdominal aortic aneurysms of similar size and may better predict rupture than diameter alone. Metabolic imaging with fluorodeoxyglucose-PET [(FDG)-PET] can identify focal aortic wall inflammation that may portend rapid progression of disease. Molecular imaging with probes that target collagen and elastin can directly exhibit changes in the vessel wall associated with disease.

The complexity of aortic disease is more fully revealed with new functional imaging techniques than with conventional anatomic analysis alone. This may better inform surveillance imaging regimens, medical management and decisions regarding early intervention for aortic disease.

The aim of this study was to evaluate the accuracy of maximum velocity measurements using volumetric phase-contrast imaging with spiral readouts in a stenotic flow phantom.

In a phantom model, maximum velocity, flow, pressure gradient, and streamline visualizations were evaluated using volumetric phase-contrast magnetic resonance imaging (MRI) with velocity encoding in one (extending on current clinical practice) and three directions (for characterization of the flow field) using spiral readouts. Results of maximum velocity and pressure drop were compared to computational fluid dynamics (CFD) simulations, as well as corresponding low-echo-time (TE) Cartesian data. Flow was compared to 2D through-plane phase contrast (PC) upstream from the restriction.

Results obtained with 3D through-plane PC as well as 4D PC at shortest TE using a spiral readout showed excellent agreements with the maximum velocity values obtained with CFD (<1 % for both methods), while larger deviations were seen using Cartesian readouts (-2.3 and 13 %, respectively). Peak pressure drop calculations from 3D through-plane PC and 4D PC spiral sequences were respectively 14 and 13 % overestimated compared to CFD.

Identification of the maximum velocity location, as well as the accurate velocity quantification can be obtained in stenotic regions using short-TE spiral volumetric PC imaging.

The type-I bicuspid aortic valve (BAV), which differs from the normal tricuspid aortic valve (TAV) most commonly by left-right coronary cusp fusion, is frequently associated with secondary aortopathies. While BAV aortic dilation has been linked to a genetic predisposition, hemodynamics has emerged as a potential alternate etiology. However, the link between BAV hemodynamics and aortic medial degeneration has not been established. The objective of this study was to compare the regional wall shear stresses (WSS) in a TAV and BAV ascending aorta (AA) and to isolate ex vivo their respective impact on aortic wall remodeling. The WSS environments generated in the convex region of a TAV and BAV AA were predicted through fluid-structure interaction (FSI) simulations in an aorta model subjected to both valvular flows. Remodeling of porcine aortic tissue exposed to TAV and BAV AA WSS for 48 h in a cone-and-plate bioreactor was investigated via immunostaining, immunoblotting and zymography. FSI simulations revealed the existence of larger and more unidirectional WSS in the BAV than in the TAV AA convexity. Exposure of normal aortic tissue to BAV AA WSS resulted in increased MMP-2 and MMP-9 expressions and MMP-2 activity but similar fibrillin-1 content and microfibril organization relative to the TAV AA WSS treatment. This study confirms the sensitivity of aortic tissue to WSS abnormalities and demonstrates the susceptibility of BAV hemodynamic stresses to focally mediate aortic medial degradation. The results provide compelling support to the important role of hemodynamics in BAV secondary aortopathy.

Aortic regurgitation (AR) is a condition associated with volume overload, causing left-ventricular (LV) remodeling, eccentric LV hypertrophy and eventually heart failure. LV remodeling associated with AR is regulated by mechanical stress, neurohormonal activation, inflammation and oxidative stress. Since anti-oxidized low-density lipoprotein (LDL) antibodies (Abs) are a measurable marker of oxidative stress, we hypothesized that an increased level of circulating oxidized LDL (oxLDL) Abs may be related to remodeling of the left ventricle in patients with significant AR.

We assessed IgG anti-oxLDL Abs in 31 patients with significant AR and compared them to 30 patients with similar risk factors and no valvular disease. Abs to oxLDL were determined by ELISA.

The 2 groups had similar clinical characteristics. There was no difference between patients with AR and patients with no AR in the level of anti-oxLDL Abs. However, in all patients and controls, anti-oxLDL Abs correlated positively with the diameter of the ascending aorta (AA; r = 0.32, p = 0.016) and the level of oxLDL Abs was significantly higher in patients with an AA diameter ≥39 mm. On multivariate analysis, only white blood cell count and AA diameter were related to anti-oxLDL Abs in all patients.

We did not find a difference in the level of anti-oxLDL Abs between patients with AR and controls; however, there was a strong correlation between anti-oxLDL Abs and AA diameter.

To determine the reproducibility of MRI aortic hemodynamic markers and to assess their relationship to aortic growth in a cohort of patients with bicuspid aortic valves (BAV).

Twenty-five patients previously studied with four-dimensional (4D) Flow imaging who had at least two separate cross-sectional imaging studies to assess for aortic growth were included: tricuspid aortic valve (TAV) controls without valvular disease (n = 12) and patients with BAV (n = 13). Flow data from the ascending aorta was used for calculation of peak velocity, normalized flow displacement, maximum wall shear stress (WSS), mean WSS, and minimal WSS. Pearson's correlation was used to evaluate interobserver agreement, and linear regression to evaluate the correlation between the different hemodynamic markers and growth. Patient informed consent was waived by the institutional review board that approved the study.

Peak velocity and flow displacement were very reproducible (r = 0.90-1.0 and r = 0.91-0.98, respectively). The range of WSS parameters was largely reproducible (0.47 < r < 0.96) with the greatest variability at the data extraction stage of analysis (0.47 < r < 0.85). Flow displacement best correlated with interval aortic growth (r = 0.65), peak velocity was moderately correlated (r = 0.35), but the WSS parameters did not correlate well with growth (r < 0.17).

Flow displacement is a simple and reproducible hemodynamic marker that shows good correlation with aortic growth in patients with bicuspid aortic valves.

Traditionally, magnetic resonance imaging (MRI) of flow using phase contrast (PC) methods is accomplished using methods that resolve single-directional flow in two spatial dimensions (2D) of an individual slice. More recently, three-dimensional (3D) spatial encoding combined with three-directional velocity-encoded phase contrast MRI (here termed 4D flow MRI) has drawn increased attention. 4D flow MRI offers the ability to measure and to visualize the temporal evolution of complex blood flow patterns within an acquired 3D volume. Various methodological improvements permit the acquisition of 4D flow MRI data encompassing individual vascular structures and entire vascular territories such as the heart, the adjacent aorta, the carotid arteries, abdominal, or peripheral vessels within reasonable scan times. To subsequently analyze the flow data by quantitative means and visualization of complex, three-directional blood flow patterns, various tools have been proposed. This review intends to introduce currently used 4D flow MRI methods, including Cartesian and radial data acquisition, approaches for accelerated data acquisition, cardiac gating, and respiration control. Based on these developments, an overview is provided over the potential this new imaging technique has in different parts of the body from the head to the peripheral arteries.

The bicuspid aortic valve (BAV) is associated with a high prevalence of calcific aortic valve disease (CAVD). Although abnormal hemodynamics has been proposed as a potential pathogenic contributor, the native BAV hemodynamic stresses remain largely unknown. Fluid-structure interaction models were designed to quantify the regional BAV leaflet wall-shear stress over the course of CAVD. Systolic flow and leaflet dynamics were computed in two-dimensional tricuspid aortic valve (TAV) and type-1 BAV geometries with different degree of asymmetry (10 and 16% eccentricity) using an arbitrary Lagrangian–Eulerian approach. Valvular performance and regional leaflet wallshear stress were quantified in terms of valve effective orifice area (EOA), oscillatory shear index (OSI) and temporal shear magnitude (TSM). The dependence of those characteristics on the degree of leaflet calcification was also investigated. The models predicted an average reduction of 49% in BAV peak-systolic EOA relative to the TAV. Regardless of the anatomy, the leaflet wall-shear stress was side-specific and characterized by high magnitude and pulsatility on the ventricularis and low magnitude and oscillations on the fibrosa. While the TAV and non-coronary BAV leaflets shared similar shear stress characteristics, the base of the fused BAV leaflet fibrosa exhibited strong abnormalities, which were modulated by the degree of calcification (6-fold, 10-fold and 16-fold TSM increase in the normal, mildly and severely calcified BAV, respectively, relative to the normal TAV). This study reveals the existence of major differences in wall-shear stress pulsatility and magnitude on TAV and BAV leaflets. Given the ability of abnormal fluid shear stress to trigger valvular inflammation, the results support the existence of a mechano-etiology of CAVD in the BAV.

About 1-2 % of the babies are born with bicuspid aortic valves instead of the normal aortic valve with three leaflets. A significant portion of the patients with the congenital bicuspid valve morphology suffer from aortic valve stenosis and/or ascending aortic dilatation and dissection thus requiring surgical intervention when they are young adults. Patients with bicuspid aortic valves (BAVs) have also been found to develop valvular stenosis earlier than those with the normal aortic valve. This paper overviews current knowledge of BAVs, where several studies have suggested that the mechanical stresses induced on the valve leaflets and the abnormal flow development in the ascending aorta may be an important factor in the diseases of the valve and the aortic root. The long-term goals of the studies being performed in our laboratory are aimed towards potential stratification of bicuspid valve patients who may be at risk for developing these pathologies based on analyzing the hemodynamic environment of these valves using fluid-structure interaction (FSI) modeling. Patient-specific geometry of the normal tri-cuspid and bicuspid valves are reconstructed from real-time 3D ultrasound images and the dynamic analyses performed in order to determine the potential effects of mechanical stresses on the valve leaflet and aortic root pathology. This paper describes the details of the computational tools and discusses challenges with patient-specific modeling.

The bicuspid aortic valve (BAV) is the most common congenital cardiac anomaly and is frequently associated with calcific aortic valve disease (CAVD). The most prevalent type-I morphology, which results from left-/right-coronary cusp fusion, generates different hemodynamics than a tricuspid aortic valve (TAV). While valvular calcification has been linked to genetic and atherogenic predispositions, hemodynamic abnormalities are increasingly pointed as potential pathogenic contributors. In particular, the wall shear stress (WSS) produced by blood flow on the leaflets regulates homeostasis in the TAV. In contrast, WSS alterations cause valve dysfunction and disease. While such observations support the existence of synergies between valvular hemodynamics and biology, the role played by BAV WSS in valvular calcification remains unknown. The objective of this study was to isolate the acute effects of native BAV WSS abnormalities on CAVD pathogenesis. Porcine aortic valve leaflets were subjected ex vivo to the native WSS experienced by TAV and type-I BAV leaflets for 48 hours. Immunostaining, immunoblotting and zymography were performed to characterize endothelial activation, pro-inflammatory paracrine signaling, extracellular matrix remodeling and markers involved in valvular interstitial cell activation and osteogenesis. While TAV and non-coronary BAV leaflet WSS essentially maintained valvular homeostasis, fused BAV leaflet WSS promoted fibrosa endothelial activation, paracrine signaling (2.4-fold and 3.7-fold increase in BMP-4 and TGF-β1, respectively, relative to fresh controls), catabolic enzyme secretion (6.3-fold, 16.8-fold, 11.7-fold, 16.7-fold and 5.5-fold increase in MMP-2, MMP-9, cathepsin L, cathepsin S and TIMP-2, respectively) and activity (1.7-fold and 2.4-fold increase in MMP-2 and MMP-9 activity, respectively), and bone matrix synthesis (5-fold increase in osteocalcin). In contrast, BAV WSS did not significantly affect α-SMA and Runx2 expressions and TIMP/MMP ratio. This study demonstrates the key role played by BAV hemodynamic abnormalities in CAVD pathogenesis and suggests the dependence of BAV vulnerability to calcification on the local degree of WSS abnormality.

The aim of this study was to evaluate the natural progression of aortic dilatation and its association with aortic valve stenosis (AoS) in patients with bicuspid aortic valve (BAV).

Prospective study of aorta dilatation in patients with BAV and AoS using cardiac magnetic resonance (CMR). Aortic root, ascending aorta, aortic peak velocity, left ventricular systolic and diastolic function and mass were assessed at baseline and at 3-year follow-up.

Of the 33 enrolled patients, 5 needed surgery, while 28 patients (17 male; mean age: 31 ± 8 years) completed the study. Aortic diameters significantly increased at the aortic annulus, sinus of Valsalva and tubular ascending aorta levels (P < 0.050). The number of patients with dilated tubular ascending aortas increased from 32 % to 43 %. No significant increase in sino-tubular junction diameter was observed. Aortic peak velocity, ejection fraction and myocardial mass significantly increased while the early/late filling ratio significantly decreased at follow-up (P < 0.050). The progression rate of the ascending aorta diameter correlated weakly with the aortic peak velocity at baseline (R (2) = 0.16, P = 0.040).

BAV patients with AoS showed a progressive increase of aortic diameters with maximal expression at the level of the tubular ascending aorta. The progression of aortic dilatation correlated weakly with the severity of AoS.

Computational fluid dynamics (CFD) simulations quantifying thoracic aortic flow patterns have not included disturbances from the aortic valve (AoV). 80% of patients with aortic coarctation (CoA) have a bicuspid aortic valve (BAV) which may cause adverse flow patterns contributing to morbidity. Our objectives were to develop a method to account for the AoV in CFD simulations, and quantify its impact on local hemodynamics. The method developed facilitates segmentation of the AoV, spatiotemporal interpolation of segments, and anatomic positioning of segments at the CFD model inlet. The AoV was included in CFD model examples of a normal (tricuspid AoV) and a post-surgical CoA patient (BAV). Velocity, turbulent kinetic energy (TKE), time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) results were compared to equivalent simulations using a plug inlet profile. The plug inlet greatly underestimated TKE for both examples. TAWSS differences extended throughout the thoracic aorta for the CoA BAV, but were limited to the arch for the normal example. OSI differences existed mainly in the ascending aorta for both cases. The impact of AoV can now be included with CFD simulations to identify regions of deleterious hemodynamics thereby advancing simulations of the thoracic aorta one step closer to reality.

Hemodynamics may play a role contributing to the progression of bicuspid aortic valve (BAV) aortopathy. This study measured the impact of BAV on the distribution of regional aortic wall shear stress (WSS) compared with control cohorts.

Local WSS distribution was measured in the thoracic aorta of 60 subjects using 4-dimensional (4D) flow-sensitive magnetic resonance imaging. WSS analysis included 15 BAV patients: 12 with fusion of the right-left coronary cusp (6 stenotic) and 3 with fusion of the right and noncoronary cusp. The right-left BAV cohort was compared with healthy subjects (n=15), age-appropriate subjects (n=15), and age-/aorta size-controlled subjects (n=15). Compared with the age-appropriate and age-/aorta size-matched controls, WSS patterns in the right-left BAV ascending aorta were significantly elevated, independent of stenosis severity (peak WSS=0.9 ± 0.3 N/m(2) compared with 0.4 ± 0.3 N/m(2) in age-/aorta size-controlled subjects; P<0.001). Time-resolved (cine) 2D images of the bicuspid valves were coregistered with 4D flow data, directly linking cusp fusion pattern to a distinct ascending aortic flow jet pattern. The observation of right-anterior ascending aorta wall/jet impingement in right-left BAV patients corresponded to regions with statistically elevated WSS. Alternative jetting patterns were observed in the right and noncoronary cusp fusion patients.

The results of this study demonstrate that bicuspid valves induced significantly altered ascending aorta hemodynamics compared with age- and size-matched controls with tricuspid valves. Specifically, the expression of increased and asymmetric WSS at the aorta wall was related to ascending aortic flow jet patterns, which were influenced by the BAV fusion pattern.

Bicuspid aortic valve (BAV) predisposes to aortic aneurysms with a high prevalence. A first hypothesis for this phenomenon is related to fibrillin deficiency (genetic hypothesis). The present article focused on a complementary, hemodynamic hypothesis stating that it is the peculiar fluid dynamics of blood in the ascending aorta of patients with BAV configurations that leads to aneurysm formation. To corroborate this hypothesis, a parametric study was performed based on numerical simulations of ascending aorta hemodynamics with different configurations of orifice area and valve orientation. The resulting wall shear stress (WSS) distributions and degree of asymmetry of the blood jet were investigated, and surrogate indices introduced. The results showed that WSS was more pronounced in subjects with BAV morphologies, also in the nonstenotic case. In particular, a maximum WSS of 3Pa was found (vs. 1.5Pa in subjects with a tricuspid configuration). It is localized at the mid-ascending aorta, the segment more prone to dilate as shown by the index related to maximum WSS (0.869 in BAV vs. 0.322 in tricuspid). Moreover, the asymmetry of the blood flow was found larger for decreasing valve area, the related index at mid-ascending aorta being more than three times higher than that found for tricuspid configuration (0.70 vs. 0.20). Further, WSS and flow asymmetry were higher also at the sinus of Valsalva and sinotubolar junction for a latero-lateral (LL) BAV configuration in keeping with the clinical observation on association between BAV configurations and different aortic aneurysm morphology. These findings may help explain the higher risk of aneurysm formation in BAV patients. The proposed indices will require validation prior to application in clinical settings.

To compare quantitative parameters for assessing the degree of eccentric systolic blood flow in the ascending thoracic aorta (AsAo).

Forty-one patients were studied with three-dimensional (3D), cine phase-contract MRI (4D Flow). Analysis was performed at peak systole for a cross-sectional plane in the AsAo just distal to the sinotubular junction. AsAo flow was graded as normal, mildly, or markedly eccentric based on qualitative visual assessment. For quantitative analysis, flow jet angle and normalized flow displacement from the vessel center were calculated.

Patients with normal AsAo systolic flow (n = 25) had an average flow jet angle of 13.7 degrees and flow displacement 0.04. These parameters were significantly elevated for patients with mild eccentric systolic flow (n = 6): 24.6 degrees (P = 0.012) and 0.12 (P = 0.001), respectively. However, for patients with marked eccentric flow (n = 10), only flow displacement was significantly elevated compared with the mild eccentric group (0.18; P = 0.04); flow angle was 25.7 degrees.

Flow displacement is a more reliable quantitative parameter for measuring eccentric AsAo systolic flow than flow jet angle, and should be evaluated in studies investigating the role of eccentric flow in the promotion of aortic pathology.

Atherosclerotic plaque in the descending thoracic aorta (dAo) is related to altered wall shear stress (WSS) for normal patients. Resection with end-to-end anastomosis (RWEA) is the gold standard for coarctation of the aorta (CoA) repair, but may lead to altered WSS indices that contribute to morbidity.

Computational fluid dynamics (CFD) models were created from imaging and blood pressure data for control subjects and age- and gender-matched CoA patients treated by RWEA (four males, two females, 15 ± 8 years). CFD analysis incorporated downstream vascular resistance and compliance to generate blood flow velocity, time-averaged WSS (TAWSS), and oscillatory shear index (OSI) results. These indices were quantified longitudinally and circumferentially in the dAo, and several visualization methods were used to highlight regions of potential hemodynamic susceptibility.

The total dAo area exposed to subnormal TAWSS and OSI was similar between groups, but several statistically significant local differences were revealed. Control subjects experienced left-handed rotating patterns of TAWSS and OSI down the dAo. TAWSS was elevated in CoA patients near the site of residual narrowings and OSI was elevated distally, particularly along the left dAo wall. Differences in WSS indices between groups were negligible more than 5 dAo diameters distal to the aortic arch.

Localized differences in WSS indices within the dAo of CoA patients treated by RWEA suggest that plaque may form in unique locations influenced by the surgical repair. These regions can be visualized in familiar and intuitive ways allowing clinicians to track their contribution to morbidity in longitudinal studies.

Although there is adequate evidence that bicuspid aortic valve (BAV) is an inheritable disorder, there is a great controversy regarding the pathogenesis of dilatation of the proximal aorta. The hemodynamic theory was the first explanation for BAV aortopathy. The genetic theory, however, has become increasingly popular over the last decade and can now be viewed as the clearly dominant one. The widespread belief that BAV disease is a congenital disorder of vascular connective tissue has led to more aggressive treatment recommendations of the proximal aorta in such patients, approaching aortic management recommendations for patients with Marfan syndrome. There is emerging evidence that the 'clinically normal' BAV is associated with abnormal flow patterns and asymmetrically increased wall stress in the proximal aorta. Recent in vitro and in vivo studies on BAV function provide a unique hemodynamic insight into the different phenotypes of BAV disease and asymmetry of corresponding aortopathy even in the presence of a 'clinically normal' BAV. On the other hand, there is a subgroup of young male patients with BAV and a root dilatation phenotype, who may present the predominantly genetic form of BAV disease. In the face of these important findings, we feel that a critical review of this clinical problem is timely and appropriate, as the prevailing BAV-aortopathy theory undoubtedly affects the surgical approach to this common clinical entity. Thorough analysis of the recent literature shows a growing amount of evidence supporting the hemodynamic theory of aortopathy in patients with BAV disease. Data from recent studies requires a reevaluation of our overwhelming support of the genetic theory, and obliges us to acknowledge that hemodynamics plays an important role in the development of this disease process. Given the marked heterogeneity of BAV disease, further studies are required in order to more precisely determine which theory is the 'correct' one for explaining the obviously different types of BAV-associated aortopathy.

To further validate the quantitative use of flow-sensitive four-dimensional velocity encoded cine magnetic resonance imaging (4D VEC MRI) for simultaneously acquired venous and arterial blood flow in healthy volunteers and for abnormal flow in patients with congenital heart disease.

Stroke volumes (SV) obtained in arterial and venous thoracic vessels were compared between standard two-dimensional (2D), 4D VEC MRI with and without respiratory navigator gating (gated/nongated) in volunteers (n = 7). In addition, SV and regurgitation fractions (RF) measured in aorta or pulmonary trunk of patients with malformed and/or insufficient valves (n = 10) were compared between 2D and nongated 4D VEC MRI methods.

In volunteers and patients, Bland-Altman tests showed excellent agreement between 2D, gated, and nongated 4D VEC MRI obtained quantitative blood flow measurements. The bias between 2D and gated 4D VEC MRI was <0.5 mL for SV; between 2D and nongated 4D VEC MRI the bias was <0.7 mL for SV and <1% for RF.

Blood flow can be quantified accurately in arterial, venous, and pathological flow conditions using 4D VEC MRI. Nongated 4D VEC MRI has the potential to be suited for clinical use in patients with congenital heart disease who require flow acquisitions in multiple vessels.

Congenital bicuspid aortic valve (BAV) is a significant risk factor for serious complications including valve dysfunction, aortic dilatation, dissection, and sudden death. Clinical tools for identification and monitoring of BAV patients at high risk for development of aortic dilatation, an early complication, are not available.

This paper reports an investigation in 18 pediatric BAV patients and 10 normal controls of links between abnormal blood flow patterns in the ascending aorta and aortic dilatation using velocity-encoded cardiovascular magnetic resonance. Blood flow patterns were quantitatively expressed in the angle between systolic left ventricular outflow and the aortic root channel axis, and also correlated with known biochemical markers of vessel wall disease.

The data confirm larger ascending aortas in BAV patients than in controls, and show more angled LV outflow in BAV (17.54 +/- 0.87 degrees) than controls (10.01 +/- 1.29) (p = 0.01). Significant correlation of systolic LV outflow jet angles with dilatation was found at different levels of the aorta in BAV patients STJ: r = 0.386 (N = 18, p = 0.048), AAO: r = 0.536 (N = 18, p = 0.022), and stronger correlation was found with patients and controls combined into one population: SOV: r = 0.405 (N = 28, p = 0.033), STJ: r = 0.562 (N = 28, p = 0.002), and AAO r = 0.645 (N = 28, p < 0.001). Dilatation and the flow jet angle were also found to correlate with plasma levels of matrix metallo-proteinase 2.

The results of this study provide new insights into the pathophysiological processes underlying aortic dilatation in BAV patients. These results show a possible path towards the development of clinical risk stratification protocols in order to reduce morbidity and mortality for this common congenital heart defect.

Bicuspid aortic valve (BAV) is often concomitant with aortic dilatation, aneurysm, and dissection. This valve lesion and its complications may affect positional and temporal wall shear stress (WSS), a parameter reported to regulate transcriptional events in vascular remodeling. Thus, this pilot study seeks to determine if the WSS in the ascending aorta (AAo) of BAV patients differs from control patients. Phase-contrast magnetic resonance imaging (PC-MRI) was used to perform flow analysis at the level of the AAo in 15 BAV and 15 control patients. Measurement of the aorta dimensions, flow rates, regurgitant fraction (RF), flow reversal ratio (FRR), temporal and spatial WSS, and shear range indices (SRI) were performed. The BAV and control group showed a significant difference between the circumferentially averaged WSS (p=0.03) and positional WSS at systole (minimum p<0.001). Regressions found that SRI (r=0.77, p<0.001), RF (r=0.68, p<0.001), and WSS at systole (r=0.66, p<0.001) were correlated to AAo size. The spatial distribution and magnitude of systolic WSS in BAV patients (-6.7+/-4.3 dynes/cm2) differed significantly from control patients (-11.5+/-6.6 dynes/cm2, p=0.03). The SRI metric, a measure of shear symmetry along the lumen circumference, was also significantly different (p=0.006) and indicated a heterogenic pattern of dilatation in the BAV patients.