Aortic Valve Hemodynamics Research Articles

Early Clinical Outcomes After Transcatheter Aortic Valve Replacement Using a Novel Self-Expanding Bioprosthesis in Patients With Severe Aortic Stenosis Who Are Suboptimal for Surgery: Results of the Evolut R U.S. Study

ObjectivesThis study sought to evaluate this transcatheter aortic valve (TAV) bioprosthesis in patients who are poorly suitable for surgical aortic valve (AV) replacement. BackgroundA novel self-expandable TAV bioprosthesis was designed to provide a low-profile delivery system, conformable annular sealing, and the ability to resheath and reposition during deployment. MethodsThe Evolut R U.S. study included 241 patients with severe aortic stenosis who were deemed to be at least high risk for surgery treated at 23 clinical sites in the United States. Clinical outcomes at 30 days were evaluated using Valve Academic Research Consortium-2 criteria. An independent echocardiography laboratory was used to evaluate hemodynamic outcomes. ResultsPatients were elderly (83.3 ± 7.2 years of age) and had high surgical risk (Society of Thoracic Surgeons predicted risk of mortality of 7.4 ± 3.4%). The majority of patients (89.5%) were treated by iliofemoral access. Resheathing or recapturing was performed in 22.6% of patients; more than 1 valve was required in 3 patients (1.3%). The 30-day outcomes included all-cause mortality (2.5%), disabling stroke (3.3%), major vascular complications (7.5%), life-threatening or disabling bleeding (7.1%), and new permanent pacemaker (16.4%). AV hemodynamics were markedly improved at 30 days: the mean AV gradient was reduced from 48.2 ± 13.0 mm Hg to 7.8 ± 3.1 mm Hg (p < 0.001) and AV area increased from 0.6 ± 0.2 cm2 to 1.9 ± 0.5 cm2 (p < 0.001). Moderate residual paravalvular leak was identified in 5.3% of patients. ConclusionsWe conclude that this novel self-expanding TAV bioprosthesis is safe and effective for the treatment of patients with severe aortic stenosis who are suboptimal for surgery. (Medtronic CoreValve Evolut R U.S. Clinical Study; NCT02207569).

Assessment of calcified aortic valve leaflet deformations and blood flow dynamics using fluid-structure interaction modeling

Abstract Aortic valve diseases are among the most common cardiovascular defects. Since a non-functioning valve results in disturbed blood flow conditions, the diagnosis of such defects is based on identification of stenosis via echocardiography. Calculation of disease parameters such as valve orifice area or transvalvular pressure gradient using echocardiography is associated with substantial errors. Computational fluid dynamics (CFD) modeling has emerged as an alternative approach for accurate assessment of aortic valve hemodynamics. Fluid-structure interaction (FSI) modeling is adapted in these models to account for counter-interacting forces of flowing blood and deforming leaflets for most accurate results. However, implementation of this approach is difficult using custom built codes and algorithms. In this paper, we present an FSI modeling methodology for aortic valve hemodynamics using a commercial modeling software, ANSYS. We simulated the problem using fluid flow solver FLUENT and structural solver MECHANICAL APDL under ANSYS and coupled the solutions using System Coupling Module to enable FSI. This approach minimized adaptation problems that would raise if separate solvers were used. As an example case, we investigated influence of leaflet calcification on hemodynamic stresses and flow patterns. Model geometries were generated using b-mode echocardiography images of an aortic valve. A Doppler velocity measurement was used as velocity inlet boundary condition in the models. Simulation results were validated by comparing leaflet movements in the simulations with b-mode echo recordings. Wall shear stress levels, pressure levels and flow patterns agree well with previous studies demonstrating the accuracy of our results. Our modeling methodology can be easily adopted by researchers that are familiar with ANSYS and other similar CFD software to investigate similar biomedical problems.

Abstract 13294: Valve Mediated Hemodynamics and Their Association With Ascending Aortic Diameter in Bicuspid Aortic Valve

Introduction: Bicuspid aortic valve (BAV) is the most common congenital heart defect, affecting 1-2% of the US population. Valve-mediated hemodynamics have been postulated to contribute to the cause and progression of ascending aorta (AAo) disease. Hypothesis: Aortic valve morphology and hemodynamics affect distal AAo diameter in subjects with BAV disease. Methods: Four-dimensional flow MRI was used to evaluate the hemodynamics in the proximal AAo of 52 subjects: size-matched controls with tricuspid aortic valves (n = 24) and BAV patients with aortic dilatation (n = 14 right and left coronary cusp fusion (RL-BAV); n = 14 right and non-coronary cusp fusion (RN-BAV)). A semi-automated technique was used to systematically quantify hemodynamic metrics (flow angle, flow displacement, and jet quadrant) and valve morphology (orifice circularity) for all subjects, as illustrated in the figure. A regression analysis was conducted to develop a relationship between upstream hemodynamics and distal AAo diameter. Results: RN-BAV subjects displayed a stronger correlation between hemodynamic metrics in the proximal AAo with diameter in the distal AAo when compared to size-matched TAV controls and RL-BAV subjects. The distal AAo diameter was found to be strongly correlated to the flow displacement (R 2 adjusted = 0.75) and flow angle (R 2 adjusted = 0.66) measured at the sino-tubular junction (STJ) in RN-BAV subjects. Orifice circularity was also strongly correlated (R 2 adjusted = 0.53) to the proximal AAo diameter in RN-BAV subjects. Conclusions: The findings in this work demonstrate that the hemodynamics in the STJ are significantly correlated to the distal AAo diameter in RN-BAV subjects. The hemodynamic metrics demonstrated more statistical significance than valve morphology when considering correlations to distal aortic size. These results could be used to design efficient imaging protocols for better prognosis of BAV-related aortopathy.

Aortic valve leaflet wall shear stress characterization revisited: impact of coronary flow

Computational characterizations of aortic valve hemodynamics have typically discarded the effects of coronary flow. The objective of this study was to complement our previous fluid–structure interaction aortic valve model with a physiologic coronary circulation model to quantify the impact of coronary flow on aortic sinus hemodynamics and leaflet wall shear stress (WSS). Coronary flow suppressed vortex development in the two coronary sinuses and altered WSS magnitude and directionality on the three leaflets, with the most substantial differences occurring in the belly and tip regions.

Calcific Aortic Valve Disease: Part 2-Morphomechanical Abnormalities, Gene Reexpression, and Gender Effects on Ventricular Hypertrophy and Its Reversibility.

In part 1, we considered cytomolecular mechanisms underlying calcific aortic valve disease (CAVD), hemodynamics, and adaptive feedbacks controlling pathological left ventricular hypertrophy provoked by ensuing aortic valvular stenosis (AVS). In part 2, we survey diverse signal transduction pathways that precede cellular/molecular mechanisms controlling hypertrophic gene expression by activation of specific transcription factors that induce sarcomere replication in-parallel. Such signaling pathways represent potential targets for therapeutic intervention and prevention of decompensation/failure. Hypertrophy provoking signals, in the form of dynamic stresses and ligand/effector molecules that bind to specific receptors to initiate the hypertrophy, are transcribed across the sarcolemma by several second messengers. They comprise intricate feedback mechanisms involving gene network cascades, specific signaling molecules encompassing G protein-coupled receptors and mechanotransducers, and myocardial stresses. Future multidisciplinary studies will characterize the adaptive/maladaptive nature of the AVS-induced hypertrophy, its gender- and individual patient-dependent peculiarities, and its response to surgical/medical interventions. They will herald more effective, precision medicine treatments.

3-Year Outcomes in High-Risk Patients Who Underwent Surgical or Transcatheter Aortic Valve Replacement

BackgroundIn patients with severe aortic stenosis at increased risk for surgery, self-expanding transcatheter aortic valve replacement (TAVR) is associated with improved 2-year survival compared with surgery. ObjectivesThis study sought to determine whether this clinical benefit was sustained over time. MethodsPatients with severe aortic stenosis deemed at increased risk for surgery by a multidisciplinary heart team were randomized 1:1 to TAVR or open surgical valve replacement (SAVR). Three-year clinical and echocardiographic outcomes were obtained in those patients with an attempted procedure. ResultsA total of 797 patients underwent randomization at 45 U.S. centers; 750 patients underwent an attempted procedure. Three-year all-cause mortality or stroke was significantly lower in TAVR patients (37.3% vs. 46.7% in SAVR; p = 0.006). Adverse clinical outcome components were also reduced in TAVR patients compared with SAVR patients, including all-cause mortality (32.9% vs. 39.1%, respectively; p = 0.068), all stroke (12.6% vs. 19.0%, respectively; p = 0.034), and major adverse cardiovascular or cerebrovascular events (40.2% vs. 47.9%, respectively; p = 0.025). At 3 years aortic valve hemodynamics were better with TAVR patients (mean aortic valve gradient 7.62 ± 3.57 mm Hg vs. 11.40 ± 6.81 mm Hg in SAVR; p < 0.001), although moderate or severe residual aortic regurgitation was higher in TAVR patients (6.8% vs. 0.0% in SAVR; p < 0.001). There was no clinical evidence of valve thrombosis in either group. ConclusionsPatients with severe aortic stenosis at increased risk for surgery had improved 3-year clinical outcomes after TAVR compared with surgery. Aortic valve hemodynamics were more favorable in TAVR patients without differences in structural valve deterioration. (Safety and Efficacy Study of the Medtronic CoreValve® System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement; NCT01240902)

Bicuspid aortic valve hemodynamics does not promote remodeling in porcine aortic wall concavity.

To investigate the role of type-I left-right bicuspid aortic valve (LR-BAV) hemodynamic stresses in the remodeling of the thoracic ascending aorta (AA) concavity, in the absence of underlying genetic or structural defects. Transient wall shear stress (WSS) profiles in the concavity of tricuspid aortic valve (TAV) and LR-BAV AAs were obtained computationally. Tissue specimens excised from the concavity of normal (non-dilated) porcine AAs were subjected for 48 h to those stress environments using a shear stress bioreactor. Tissue remodeling was characterized in terms of matrix metalloproteinase (MMP) expression and activity via immunostaining and gelatin zymography. Immunostaining semi-quantification results indicated no significant difference in MMP-2 and MMP-9 expression between the tissue groups exposed to TAV and LR-BAV AA WSS (P = 0.80 and P = 0.19, respectively). Zymography densitometry revealed no difference in MMP-2 activity (total activity, active form and latent form) between the groups subjected to TAV AA and LR-BAV AA WSS (P = 0.08, P = 0.15 and P = 0.59, respectively). The hemodynamic stress environment present in the concavity of type-I LR-BAV AA does not cause any significant change in proteolytic enzyme expression and activity as compared to that present in the TAV AA.

Regression of Paravalvular Aortic Regurgitation and Remodeling of Self-Expanding Transcatheter Aortic Valve: An Observation From the CoreValve U.S. Pivotal Trial

ObjectivesThe aim of this study was to describe the natural history and clinical importance of paravalvular aortic regurgitation (PVAR) after CoreValve transcatheter aortic valve replacement (TAVR) and to relate these findings to the structural and hemodynamic changes documented by serial echocardiographic analysis. BackgroundPVAR after TAVR with the self-expanding CoreValve bioprosthesis has been shown to regress over time, but the time course and the mechanism of PVAR regression has not been completely characterized. MethodsPatients with severe aortic stenosis who underwent CoreValve TAVR and followed up to 1 year in the multicenter CoreValve U.S. Pivotal Trial (Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement) were studied. Serial echocardiography studies were analyzed by an echocardiographic core laboratory. Annular sizing ratio was calculated from computed tomography measurements. Paired, as well as total, data were compared. ResultsThe CoreValve was implanted in 634 patients with a mean age of 82.7 ± 8.4 years. After a marked improvement noted at discharge, aortic valve velocity, mean gradient, and effective orifice area further improved significantly at 1 month (2.08 ± 0.45 m/s vs. 1.99 ± 0.46 m/s, p < 0.0001, 9.7 ± 4.4 mm Hg vs. 8.9 ± 4.6 mm Hg, p < 0.0001, and 1.78 ± 0.51 cm2 vs. 1.85 ± 0.58 cm2, p = 0.03, respectively). The improvement was sustained through 1 year. PVAR was moderate or severe in 9.9%, and of 36 patients with moderate PVAR at discharge and paired data, 30 (83%) improved at least 1 grade of regurgitation at 1 year. Annular sizing ratio was significantly associated with the degree of PVAR. ConclusionsThere was further improvement in aortic prosthetic valve hemodynamics and regression of PVAR up to 1 year compared with discharge after TAVR with CoreValve. These changes are possibly due to remodeling and outward expansion of the self-expandable CoreValve with nitinol frame. (Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement [Medtronic CoreValve U.S. Pivotal Trial]; NCT01240902)

A novel computational model for the hemodynamics of bileaflet mechanical valves in the opening phase.

A powerful alternative means to study the hemodynamics of bileaflet mechanical heart valves is the computational fluid dynamics method. It is well recognized that computational fluid dynamics allows reliable physiological blood flow simulation and measurements of flow parameters. To date, in almost all of the modeling studies on the hemodynamics of bileaflet mechanical heart valves, a velocity (mass flow)-based boundary condition and an axisymmetric geometry for the aortic root have been assigned, which, to some extent, are erroneous. Also, there have been contradictory reports of the profile of velocity in downstream of leaflets, that is, in some studies, it is suggested that the maximum blood velocity occurs in the lateral orifice, and in some other studies, it is postulated that the maximum velocities in the main and lateral orifices are identical. The reported values for the peak velocities range from 1 to 3 m/s, which highly depend on the model assumptions. The objective of this study is to demonstrate the importance of the exact anatomical model of the aortic root and the realistic boundary conditions in the hemodynamics of the bileaflet mechanical heart valves. The model considered in this study is based on the St Jude Medical valve in a novel modeling platform. Through a more realistic geometrical model for the aortic root and the St Jude Medical valve, we have developed a new set of boundary conditions in order to be used for the assessment of the hemodynamics of aortic bileaflet mechanical heart valves. The results of this study are significant for the design improvement of conventional bileaflet mechanical heart valves and for the design of the next generation of prosthetic valves.

Characterization of the relationship between bicuspid aortic valve morphology and hemodynamics

Background Bicuspid aortic valve (BAV) is the most common congenital heart defect affecting 1-2% of the US population. BAV has been associated with progressive secondary pathologies, such as aortic valve calcification, stenosis, regurgitation, aortic root dilatation, and/or aortic aneurysm. However, not all patients exhibit symptoms or develop aortopathy and the exact link between BAV morphology and disease progression is not fully understood. Magnetic resonance imaging (MRI) has been previously used to characterize BAV hemodynamics. However, studies have been hampered by the need for lengthy manual data analysis thereby limiting reproducibility and/or integration into a clinically feasible workflow.

PS1-17 Quantifying the interplay between bicuspid aortic valve and aortic hemodynamics : an integrative computational study(PS1: Poster Short Presentation I,Poster Session)

PS1-17 Quantifying the interplay between bicuspid aortic valve and aortic hemodynamics : an integrative computational study(PS1: Poster Short Presentation I,Poster Session)

MRI-based Protocol to Characterize the Relationship Between Bicuspid Aortic Valve Morphology and Hemodynamics

Bicuspid aortic valve (BAV) is the most common congenital heart defect and can lead to severe complications. Many studies have been conducted to evaluate the potential of geometric and hemodynamic biomarkers to predict BAV-related aortopathy. This work proposes a novel semi-automatic protocol to characterize geometry and hemodynamics of aorta and aortic valve based on 2D cine and 4D flow MRI data. The protocol was applied to 12 BAV and 12 control subjects. Statistical differences between the groups were identified and linear regression models were investigated to elucidate the potential of this protocol to investigate the risk of disease progression. Statistical differences between the groups were found for orifice eccentricity, aorta diameter, velocity, jet angle and flow displacement. Key findings of the regression analysis include the association in the proximal ascending aorta between aorta diameter and mean velocity (negative), jet angle (positive) and flow displacement (positive), in the combined cohort. Positive association between flow displacement in the proximal aorta and orifice jet angle in TAV subjects was found. This study represents a pilot application of a protocol for standardized assessment of aortic geometry and hemodynamics associated with BAV disease. Its limited need for user input is advantageous for large cohort studies.

Early effects of transcatheter aortic valve implantation and aortic valve replacement on myocardial function and aortic valve hemodynamics: Insights from cardiovascular magnetic resonance imaging

There remains a paucity of mechanistic data on the effect of transcatheter aortic valve implantation (TAVI) on early left and right ventricular function and quantitative aortic valve regurgitation. We sought to assess and compare the early effects on myocardial function and aortic valve hemodynamics of TAVI and aortic valve replacement (AVR) using serial cardiovascular magnetic resonance (CMR) imaging and echocardiography. A prospective comparison study of 47 patients with severe aortic stenosis undergoing either TAVI (n = 26) or high-risk AVR (n = 21). CMR (for left ventricle/right ventricle function, left ventricular mass, left atrial volume, and aortic regurgitation) was carried out before the procedure and early postprocedure (<14 days). Groups were similar with respect to Society of Thoracic Surgeons score (TAVI, 7.7 vs AVR, 5.9; P = .11). Preoperative left ventricular (TAVI, 69% ± 13% vs AVR, 73% ± 10%; P = .10) and right ventricular (TAVI, 61% ± 11% vs AVR, 59% ± 8%; P = .5) ejection fractions were similar. Postoperative left ventricular ejection fraction was preserved in both groups. In contrast, decline in right ventricular ejection fraction was more significant in the TAVI group (61%-54% vs 59%-58%; P = .01). Postprocedure aortic regurgitant fraction was significantly greater in the TAVI group (16% vs 4%; P = .001), as was left atrial size (110 vs 84 mL; P = .02). Further analysis revealed a significant relationship between the increased aortic regurgitant fraction and greater left atrial size (P = .006), and a trend toward association between the decline in right ventricle dysfunction and increased postprocedure aortic regurgitation (P = .08). There was no significant difference in early left ventricular systolic function between techniques. Whereas right ventricle systolic function was preserved in the AVR group, it was significantly impaired early after TAVI, possibly reflecting a clinically important pathophysiologic consequence of paravalvular aortic regurgitation.

Impact of Flow and Left Ventricular Strain on Outcome of Patients With Preserved Left Ventricular Ejection Fraction and Low Gradient Severe Aortic Stenosis Undergoing Aortic Valve Replacement

The prognostic implications of flow, assessed by stroke volume index (SVi), and left ventricular (LV) global longitudinal strain on survival of patients with low-gradient severe aortic stenosis (AS) and preserved LV ejection fraction are debated. The aim of this study was to evaluate the impact of flow and LV global longitudinal strain on survival in these patients treated with aortic valve replacement (AVR). Patients with low-gradient severe AS with preserved LV ejection fraction treated with AVR (n= 134, mean age 76 ± 10years, 50% men) were included in the present study. Aortic valve hemodynamics and LV function were assessed with 2-dimensional, Doppler and speckle-tracking echocardiography before AVR. Patients were dichotomized on the basis of low (SVi ≤35ml/m(2)) or normal (SVi >35ml/m(2)) flow and impaired (>-15%) or more preserved (≤-15%) global longitudinal strain. The end point was all-cause mortality. During a median follow-up period of 1.8years (interquartile range 0.5 to 3) after AVR, 26 patients (19.4%) died. Survival was better for patients with SVi >35ml/m(2) or global longitudinal strain ≤-15% compared with those with SVi ≤35ml/m(2) or global longitudinal strain >-15% (log-rank p= 0.01). Atrial fibrillation (hazard ratio 5.40, 95% confidence interval 1.81 to 16.07, p= 0.002) and chronic kidney disease (hazard ratio 3.67, 95% confidence interval 1.49 to 9.06, p= 0.005) were the clinical variables independently associated with all-cause mortality. The addition of global longitudinal strain (chi-square= 19.87, p= 0.029, C-statistic= 0.74) or SVi (chi-square= 29.62, p <0.001, C-statistic= 0.80) to a baseline model including atrial fibrillation and chronic kidney disease (chi-square= 14.52, C-statistic= 0.68) improved risk stratification of these patients. In conclusion, flow and LV global longitudinal strain are independently associated with survival after AVR in patients with low-gradient severe AS with preserved LV ejection fraction.

An In Vitro Evaluation of the Impact of Eccentric Deployment on Transcatheter Aortic Valve Hemodynamics

Patients with aortic stenosis present with calcium deposits on the native aortic valve, which can result in non-concentric expansion of Transcatheter Aortic Valve Replacement (TAVR) stents. The objective of this study is to evaluate whether eccentric deployment of TAVRs lead to turbulent blood flow and blood cell damage. Particle Image Velocimetry was used to quantitatively characterize fluid velocity fields, shear stress and turbulent kinetic energy downstream of TAVRs deployed in circular and eccentric orifices representative of deployed TAVRs in vivo. Effective orifice area (EOA) and mean transvalvular pressure gradient (TVG) values did not differ substantially in circular and eccentric deployed valves, with only a minor decrease in EOA observed in the eccentric valve (2.0cm(2) for circular, 1.9cm(2) for eccentric). Eccentric deployed TAVR lead to asymmetric systolic jet formation, with increased shear stresses (circular=97N/m(2) vs. eccentric=119N/m(2)) and regions of turbulence intensity (circular=180N/m(2) vs. eccentric=230N/m(2)) downstream that was not present in the circular deployed TAVR. The results of this study indicate that eccentric deployment of TAVRs can lead to altered flow characteristics and may potentially increase the hemolytic potential of the valve, which were not captured through hemodynamic evaluation alone.

IMPACT OF FLOW AND LEFT VENTRICULAR SYSTOLIC FUNCTION ON OUTCOME OF PATIENTS WITH PRESERVED LEFT VENTRICULAR EJECTION FRACTION AND LOW GRADIENT SEVERE AORTIC VALVE STENOSIS UNDERGOING AORTIC VALVE REPLACEMENT

The prognostic implications of flow, assessed by stroke volume index (SVi), and left ventricular (LV) global longitudinal strain on survival of patients with low-gradient severe aortic stenosis (AS) and preserved LV ejection fraction are debated. The aim of this study was to evaluate the impact of flow and LV global longitudinal strain on survival in these patients treated with aortic valve replacement (AVR). Patients with low-gradient severe AS with preserved LV ejection fraction treated with AVR (n [ 134, mean age 76 – 10 years, 50% men) were included in the present study. Aortic valve hemodynamics and LV function were assessed with 2-dimensional, Doppler and speckle-tracking echocardiography before AVR. Patients were dichotomized on the basis of low (SVi £35 ml/m 2 ) or normal (SVi >35 ml/m 2 ) flow and impaired (>L15%) or more preserved (£L15%) global longitudinal strain. The end point was all-cause mortality. During a median follow-up period of 1.8 years (interquartile range 0.5 to 3) after AVR, 26 patients (19.4%) died. Survival was better for patients with SVi >35 ml/m 2 or global longitudinal strain £L15% compared with those with SVi £35 ml/m 2 or global longitudinal strain >L15% (log-rank p [ 0.01). Atrial fibrillation (hazard ratio 5.40, 95% confidence interval 1.81 to 16.07, p [ 0.002) and chronic kidney disease (hazard ratio 3.67, 95% confidence interval 1.49 to 9.06, p [ 0.005) were the clinical variables independently associated with all-cause mortality. The addition of global longitudinal strain (chi-square [ 19.87, p [ 0.029, C-statistic [ 0.74) or SVi (chi-square [ 29.62, p <0.001, C-statistic [0.80) to a baseline model including atrial fibrillation and chronic kidney disease (chi-square [ 14.52, C-statistic [ 0.68) improved risk stratification of these patients. In conclusion, flowandLVglobal longitudinalstrainareindependently associatedwith survival after AVR in patients with low-gradient severe AS with preserved LV ejection fraction. 2014 Elsevier Inc. All rights reserved. (Am J Cardiol 2014;114:1875e1881)

Bicuspid aortic valve hemodynamics induces abnormal medial remodeling in the convexity of porcine ascending aortas

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 48h 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.

Combining numerical and clinical methods to assess aortic valve hemodynamics during exercise

Computational simulations have the potential to aid understanding of cardiovascular hemodynamics under physiological conditions, including exercise. Therefore, blood hemodynamic parameters during different heart rates, rest and exercise have been investigated, using a numerical method. A model was developed for a healthy subject. Using geometrical data acquired by echo-Doppler, a two-dimensional model of the chamber of aortic sinus valsalva and aortic root was created. Systolic ventricular and aortic pressures were applied as boundary conditions computationally. These pressures were the initial physical conditions applied to the model to predict valve deformation and changes in hemodynamics. They were the clinically measured brachial pressures plus differences between brachial, central and left ventricular pressures. Echocardiographic imaging was also used to acquire different ejection times, necessary for pressure waveform equations of blood flow during exercise. A fluid-structure interaction simulation was performed, using an arbitrary Lagrangian-Eulerian mesh. During exercise, peak vorticity increased by 14.8%, peak shear rate by 15.8%, peak cell Reynolds number by 20%, peak leaflet tip velocity increased by 47% and the blood velocity increased by 3% through the leaflets, whereas full opening time decreased by 11%. Our results show that numerical methods can be combined with clinical measurements to provide good estimates of patient-specific hemodynamics at different heart rates.

Valvular heart team.

Valvular heart team.

Assessment of aortic valve pressure overload and leaflet functions in an ex vivo beating heart loaded with a continuous flow cardiac assist device

Aortic valve regurgitation, fusion and thrombosis are commonly reported clinical complications after continuous flow ventricular assist device implantations; however, the complex interaction between reduced pulsatile flow physiology and aortic valve functions has not been studied experimentally. To address this, a continuous flow left ventricular assist device was implanted in four swine ex vivo beating hearts and then operated at baseline (device off, no flow) and at device speeds ranging between 8500 and 11,500 rpm under healthy and experimentally created failing heart conditions. At baseline and after each speed increase, aortic, left ventricular, left atrial and pulse pressure signals were monitored to assess the haemodynamic status of the ex vivo heart, aortic valve opening time and the transvalvular pressure changes. Aortic root and device flows were recorded with flow probes. Left ventricular pressure-volume loops were measured with a conductance catheter. Changes in aortic leaflet motion and end-diastolic aortic root diameter were recorded with epicardial echocardiography. A two-chamber healthy and failing ex vivo beating heart model was successfully created. At increasing device flows, aortic valve open time steadily decreased from 36±7% of the baseline cardiac cycle to 0% at 11,500 rpm in the healthy heart and from 18±16 to 0% in failing heart mode (P<0.05). Aortic transvalvular pressure increased from 25±5 mmHg (baseline) to 67±7 mmHg (11,500 rpm) in the healthy heart and from 10±9 mmHg (baseline) to 73±8 mmHg (11,500 rpm) in failing heart mode (P<0.05). Aortic root diameters were significantly increased at speeds exceeding 10 500 rpm in the healthy heart mode (P<0.05 vs baseline) and approached statistical significance in failing hearts. Increasing assist device flows resulted in pressure overload above the aortic leaflets, impaired leaflet functions, caused aortic root dilatation and altered leaflet coaptation at the central portion of the aortic valve in both modes. We conclude that the deleterious effect of the reduced pulsatile flow on the aortic valve functions and haemodynamics is immediate and such an insult may explain the structural changes of the aortic valve causing leaflet fusion and/or regurgitation in the chronic phase.