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Aortic Valve Leaflet Wall Shear Stress Characterization Revisited: Impact of Coronary Flow

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Computer Methods In Biomechanics & Bio Engineering
Authors:
Kai Cao at University of Notre Dame
Kai Cao
Philippe Sucosky at Kennesaw State University
Philippe Sucosky
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Abstract and Figures

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.
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Computer Methods in Biomechanics and Biomedical
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ISSN: 1025-5842 (Print) 1476-8259 (Online) Journal homepage: http://www.tandfonline.com/loi/gcmb20
Aortic valve leaflet wall shear stress
characterization revisited: impact of coronary flow
K. Cao & P. Sucosky
To cite this article: K. Cao & P. Sucosky (2016): Aortic valve leaflet wall shear stress
characterization revisited: impact of coronary flow, Computer Methods in Biomechanics and
Biomedical Engineering, DOI: 10.1080/10255842.2016.1244266
To link to this article: http://dx.doi.org/10.1080/10255842.2016.1244266
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COMPUTER METHODS IN BIOMECHANICS AND BIOMEDICAL ENGINEERING, 2016
http://dx.doi.org/10.1080/10255842.2016.1244266
Aortic valve leaet wall shear stress characterization revisited: impact of
coronary ow
K. Caoa and P. Sucoskyb
aDepartment of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN, USA; bDepartment of Mechanical and
Materials Engineering, Wright State University, Dayton, OH, USA
ABSTRACT
Computational characterizations of aortic valve hemodynamics have typically discarded the eects
of coronary ow. The objective of this study was to complement our previous uid–structure
interaction aortic valve model with a physiologic coronary circulation model to quantify the impact
of coronary ow on aortic sinus hemodynamics and leaet wall shear stress (WSS). Coronary ow
suppressed vortex development in the two coronary sinuses and altered WSS magnitude and
directionality on the three leaets, with the most substantial dierences occurring in the belly and
tip regions.
1. Introduction
Aortic valve (AV) leaets are sensitive to their surround-
ing hemodynamic stress environment. While physiologic
ow promotes AV homeostasis, wall shear stress (WSS)
abnormalities trigger pathological cascades that may lead
ultimately to calcic aortic valve disease (CAVD) (Sucosky
et al. 2009; Hoehn et al. 2010; Sun et al. 2012, 2013; Sun &
Sucosky 2015). is hypothetical hemodynamic etiology of
valvular disease has motivated the characterization of the
native leaet WSS environment using uid–structure inter-
action (FSI) modeling (Chandra et al. 2012; Cao & Sucosky
2015; Gilmanov & Sotiropoulos 2016; Cao & Sucosky
forthcoming 2016). While those studies have shed new light
on valvular mechanics and function, the impact of the cor-
onary circulation on valvular ow has been discarded. As
observed experimentally, the coronary ow established dur-
ing diastole generates complex vortex dynamics in the aortic
sinus, which interacts with the leaets and may alter their
regional stress distribution (Moore & Dasi 2015). e aim
of this study was to complement our previous FSI AV model
with a physiologic coronary circulation model to quantify
the impact of coronary ow on AV ow and leaet WSS.
2. Materials and methods
Our previous FSI AV model (Cao et al. 2016) was used
as the basis for this study. e aortic root geometry was
modied to include the coronary ostia and the proximal
segments of the coronary arteries. e le- and right-cor-
onary ostia were modeled as circular (diameter: 4.0 and
3.2mm, respectively) and were positioned 18mm above
the valve annulus (Waller et al. 1992) (Figure 1(a)). e
proximal le- and right-coronary arteries (LCA and RCA,
respectively) were modeled as cylindrical extensions
(length: 6.0mm) with a wall thickness of 0.4mm (Dong et
al. 2015). e coronary arteries were approximated as iso-
tropic linear elastic materials (Young’s modulus: 0.4MPa,
Claes et al. 2010).
Two Windkessel models were implemented to pre-
scribe realistic LCA and RCA ow rates (Q):
where P is the aortic pressure, R1 is the coronary arterial
resistance, R2 is the coronary venous resistance and C is
the coronary arterial compliance (Figure 1(b)) (Westerhof
et al. 2009). Each model was calibrated using two sets of
parameters (Table 1) to generate physiologic human cor-
onary ow rates during systole and diastole, respectively
(Koeppen & Stanton 2009) (Figure 1(c)).
Arbitrary Lagrangian Eulerian simulations were car-
ried out in ANSYS 15.0 over three cardiac cycles and all
results were extracted during the last cycle. All model
parameters, numerical treatments and mesh sensitivity
analyses have been described in our previous FSI AV
(1)
CR
1
dQ
dt+
(
1+
R
1
R
2)
Q=CdP
dt+1
R
2
P
,
KEYWORDS
Aortic valve; coronary flow;
fluid–structure interaction;
hemodynamics; wall shear
stress; aortic sinus
ARTICLE HISTORY
Received 4 May 2016
Accepted 29 September 2016
© 2016 Informa UK Limited, trading as Taylor & Francis Group
CONTACT P. Sucosky philippe.sucosky@wright.edu
The supplementary material for this paper is available online at http://dx.doi.org/10.1080/10255842.2016.1244266.
2 K. CAO AND P. SUCOSKY
3. Results
Coronary ow resulted in asymmetric hemodynamics in
the aortic sinuses during diastole, marked by recirculation
and intense vorticity in the non-coronary sinus and more
moderate vorticity in the coronary sinuses (Figure 2(a)
and Supplemental Material – video.mp4). Quantication
of the peak-systolic valve geometric orice area (GOA)
revealed a 7% increase in the presence of coronary ow
model (Cao et al. 2016). Valvular ow was characterized in
terms of vorticity and velocity. Regional WSS magnitude
and directionality were quantied in terms of temporal
shear magnitude (TSM) and oscillatory shear index (OSI)
in the base, belly and tip of the non-, right- and le-cor-
onary leaets (i.e. NC, RC and LC leaets, respectively)
and compared to those captured by our previous model
in the absence of coronary ow (REF leaet).
Figure 1.Model setup: (a) AV geometry; (b) Windkessel electrical analog; and (c) coronary flow rates generated by the Windkessel models
at the LCA and RCA outlets (physiologic values adapted from Koeppen & Stanton 2009).
Table 1.Windkessel parameters.
Systole Diastole
R1 (kg/(m4s) R2 (kg/(m4s) C (m4s2/kg) R1 (kg/(m4s) R2 (kg/(m4s) C (m4s2/kg)
LCA 5.7 × 1091.9 × 1011 4.9 × 10−11 3.8 × 1092.1 × 1011 9.7 × 10−11
RCA 1.7 × 1010 5.7 × 1011 1.6 × 10−11 3.9 × 1010 1.9 × 1011 9.6 × 10−12
Figure 2.Comparison of AV hemodynamics without and with coronary flow: (a) diastolic velocity and vorticity fields; (b) TSM and (c) OSI
regional distributions on the leaflet fibrosa.
COMPUTER METHODS IN BIOMECHANICS AND BIOMEDICAL ENGINEERING 3
relative to our previous model (Supplemental Material
– Figure S1), demonstrating the benecial impact of the
coronary circulation on valvular function.
As compared to our previous model, coronary ow
generated an overall increase in WSS magnitude and uni-
directionality on the leaet brosa (up to 30% increase
in TSM, up to 0.10 decrease in OSI vs. REF leaet), with
the most apparent changes occurring in the belly and
tip regions (Figure 2(b) and (c)). e asymmetry in vor-
ticity dynamics introduced by the coronary circulation
translated into discrepancies in WSS magnitude and
directionality between the three leaets. e LC and RC
leaets were subjected to WSS overloads (30 and 15%
increase, respectively) relative to the NC leaet. While
this increase aected the belly and tip of the LC leaet, it
only occurred in the tip of the RC leaet. Coronary ow
also generated asymmetric and spatially-dependent OSI
distributions on the leaets, with mixed directionality in
the base (0.26<OSI<0.30), more pronounced bidirec-
tionality in the belly (OSI>0.31) and strong unidirec-
tionality in the tip (OSI<0.15). While WSS directionality
was essentially similar in the base of all three leaets, it
was markedly more bidirectional in the belly of the RC
and NC leaets (0.13 and 0.12 OSI increase, respectively)
relative to the LC leaet and more unidirectional in the
tip of the LC and RC leaets (0.09 OSI decrease) relative
to the NC leaet.
4. Discussion
In summary, coronary ow suppressed vortex devel-
opment in the coronary sinuses and promoted valvular
function. ose results are consistent with particle image
velocimetry measurements of aortic sinus ow with phys-
iologic coronary ow (Moore & Dasi 2015). Coronary
ow resulted in contrasted WSS patterns on the three
leaets, with the most substantial dierences occurring
in the belly and tip regions. e distinctly lower and more
bidirectional WSS on the NC leaet may explain its higher
vulnerability to calcication (Freeman & Otto 2005). To
conclude, coronary ow impacts the leaet WSS environ-
ment and should be accounted for in the characterization
of the native valvular hemodynamic stresses.
Disclosure statement
No potential conict of interest was reported by the authors.
Funding
is work supported by Division of Civil, Mechanical and Man-
ufacturing Innovation, National Science Foundation [grant
number CMMI-1148558], [grant number CMMI-1550144];
American Heart Association [grant number 14PRE18940010].
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Supplementary resource (1)

Animation of valvular flow velocity vector and vorticity contour fields without coronary flow and with coronary flow in the left-, right- and non-coronary sinuses (coronal view). Playback speed is half the actual speed. Vorticity scale: -300 /s (blue); +300 /s (red).
Data
October 2016
Kai Cao · Philippe Sucosky
... 4 AV diseases. [6][7][8] Preliminary data suggest that a large aortic root aneurysm is a risk factor for the failure of a valve-sparing aortic root replacement (VSARR), highlighting the detrimental effects of a large aneurysm on the leaflet. 9, 10 We hypothesized that an aortic root aneurysm would alter the fluid dynamics around the AV, placing abnormal mechanical stress on the leaflets. ...
... Second, while we included the patients who underwent CABG as controls, mechanical stress on the AV could be abnormal due to decreased coronary flow and co-existing atherosclerotic changes of the aorta or the AV leaflets. 6 We mitigated these concerns by selecting the belly of the non-coronary cusp to minimize the effects of coronary flow and by excluding patients with any abnormal appearance of the aortic root and valve. Our methodology required the using an epiaortic echocardiogram, so we selected a control cohort from the patients who were undergoing open-heart surgery. ...
Influence of aneurysmal aortic root geometry on mechanical stress to the aortic valve leaflet
Article
  • Feb 2021
Aims While mechanical stress caused by blood flow, e.g. wall shear stress (WSS), and related parameters, e.g. oscillatory shear index (OSI), are increasingly being recognized as key moderators of various cardiovascular diseases, studies on valves have been limited because of a lack of appropriate imaging modalities. We investigated the influence of aortic root geometry on WSS and OSI on the aortic valve (AV) leaflet. Methods and results We applied our novel approach of intraoperative epi-aortic echocardiogram to measure the haemodynamic parameters of WSS and OSI on the AV leaflet. Thirty-six patients were included, which included those who underwent valve-sparing aortic root replacement (VSARR) with no significant aortic regurgitation (n = 17) and coronary artery bypass graft (CABG) with normal AV (n = 19). At baseline, those who underwent VSARR had a higher systolic WSS (0.52 ± 0.12 vs. 0.32 ± 0.08 Pa, respectively, P < 0.001) and a higher OSI (0.37 ± 0.06 vs. 0.29 ± 0.04, respectively, P < 0.001) on the aortic side of the AV leaflet than those who underwent CABG. Multivariate regression analysis revealed that the size of the sinus of Valsalva had a significant association with WSS and OSI. Following VSARR, WSS and OSI values decreased significantly compared with the baseline values (WSS: 0.29 ± 0.12 Pa, P < 0.001; OSI: 0.26 ± 0.09, P < 0.001), and became comparable to the values in those who underwent CABG (WSS, P = 0.42; OSI, P = 0.15). Conclusions Mechanical stress on the AV gets altered in correlation with the size of the aortic root. An aneurysmal aortic root may expose the leaflet to abnormal fluid dynamics. The VSARR procedure appeared to reduce these abnormalities.
View
... This technique aims to restore a near normal AR size, geometry and possibly dynamics through the preservation of the 'leaflet-sinus' unit, i.e. the continuity between the leaflet and sinus of Valsalva, by sheathing the AR with a sinus-shaped graft. AV leaflet kinematics depends on AR geometry [2,12,13] and dynamics [4,14,15] as well as transvalvular flow, heart rate, aortic pressure and coronary flow [16,17]. ...
... The first part is featured by a slow movement of the leaflets towards the AR axis, while the second phase is characterized by a fast, quasi impulsive movement of the leaflets which ends with complete valve closure. Similar to the opening, the closing phase is driven by the time variation of the pressure difference across the leaflets, and additionally depends upon mechanical properties of the AR structures [15,20], coronary flow [16,17] and geometry of the sinuses of Valsalva with vortexes formation. Our findings, as for the Yacoub technique during the closure phase, are in agreement with those reported by Fries et al. [3] and confirmed that this technique does not significantly influence the time interval and velocity of both slow and rapid closing phases, but rather affects the leaflets position as shown by the breadth of the leaflets displacement distance or D 2 . ...
Leaflet kinematics after the Yacoub and Florida-sleeve operations: results of an in vitro study
Article
  • Nov 2020
OBJECTIVES The Florida-sleeve is a valve-sparing technique that causes minimal interference to leaflet kinematics and aortic root dynamism. The aim of this in vitro study was to evaluate the effects of the Florida-sleeve and Yacoub techniques on aortic leaflet kinematics. METHODS Two groups of 6 whole porcine hearts were treated with either the Florida-sleeve technique or the Yacoub technique and tested in a pulsatile loop. Valve fluid dynamics, coronary flow analysis and valve echocardiograms were performed both before and after the procedures. RESULTS Both procedures showed no difference in rapid valve opening time as compared with their respective baseline values. The Florida-sleeve procedure showed a shorter slow closing time (192 ± 19 ms vs baseline 244 ± 14 ms, P = 0.016) and increased slow closing velocity (−1.5 ± 0.4 cm/s vs baseline −0.8 ± 0.4 cm/s, P = 0.038). In the rapid valve closing phase, the Yacoub procedure showed a trend towards slower closing valve velocity (−16 ± 9 cm/s vs baseline −25 ± 9 cm/s, P = 0.07). The Yacoub procedure showed larger leaflet displacement at the end of the slow valve closing time that was 2.0 ± 0.5 cm vs baseline 1.5 ± 0.3 cm, P = 0.044. When comparing the Florida-sleeve and Yacoub procedures, the former showed statistically significant shorter slow valve closing time (P = 0.017). CONCLUSIONS This study showed that the Florida-sleeve technique alters the slow closing phase of the aortic valve leaflet kinematics when compared with both the normal baseline and Yacoub procedure, while the latter showed a larger leaflet displacement before the rapid closing valve phase.
View
... Coronary flow may alter the WSS on the leaflets. 21 Therefore, the belly (middle of the leaflet) of the noncoronary cusp was chosen for the representative WSS value on the AV ( Figure 1, C-F). The sinus of Valsalva, where the diameter was the largest, and 1-2 cm above the S-T junction and below the LVAD outflow cannula were chosen to calculate the WSS of the root and ascending aorta, respectively. ...
Left Ventricular Assist Device Support-Induced Alteration of Mechanical Stress on Aortic Valve and Aortic Wall
Article
  • Jul 2021
  • ASAIO J
The aim of this study was to evaluate the fluid dynamics in the aortic valve and proximal aorta during continuous-flow left ventricular assist device (LVAD) support using epiaortic echocardiography and vector flow mapping technology. A total of 12 patients who underwent HeartMate 3 implantation between December 2018 and February 2020 were prospectively examined. The wall shear stress (WSS) on the ascending aorta, aortic root, and aortic valve was evaluated before and after LVAD implantation. The median age of the cohort was 62 years and 17% were women. The peak WSS on the ascending aorta (Pre 1.48 [0.86-1.69] [Pascal {Pa}] vs. Post 0.33 [0.21-0.58] [Pa]; p = 0.002), aortic root (Pre 0.46 [0.31-0.58] (Pa) vs. Post 0.18 [0.12-0.25] (Pa); p = 0.001), and ventricularis of the aortic valve (Pre 1.76 [1.59-2.30] (Pa) vs. Post 0.30 [0.10-0.61] (Pa); p = 0.001) was significantly lower after LVAD implantation. No difference in WSS was observed on the fibrosa of the aortic valve (Pre 0.36 [0.22-0.53] (Pa) vs. Post 0.38 [0.38-0.52] (Pa); p = 0.850) before and after implantation. The WSS on the ascending aorta, aortic root, and ventricularis of the aortic valve leaflets was significantly altered by LVAD implantation, providing preliminary data on the potential contribution of fluid dynamics to LVAD-induced aortic insufficiency and root thrombus.
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... However, one study suggested mostly unidirectional, nonoscillatory shear stress on the aortic side of the valve due to sinus vortices (29). These vortices may not develop when diastolic coronary blood flow is present (30). Shear stresses are lowest on the fibrosa side of the non-coronary leaflet due to the lack of diastolic coronary flow (4), and interestingly, the non-coronary leaflet has the highest susceptibility to calcification (4). ...
Dissecting Calcific Aortic Valve Disease—The Role, Etiology, and Drivers of Valvular Fibrosis
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  • May 2021
Calcific aortic valve disease (CAVD) is a highly prevalent and progressive disorder that ultimately causes gradual narrowing of the left ventricular outflow orifice with ensuing devastating hemodynamic effects on the heart. Calcific mineral accumulation is the hallmark pathology defining this process; however, fibrotic extracellular matrix (ECM) remodeling that leads to extensive deposition of fibrous connective tissue and distortion of the valvular microarchitecture similarly has major biomechanical and functional consequences for heart valve function. Significant advances have been made to unravel the complex mechanisms that govern these active, cell-mediated processes, yet the interplay between fibrosis and calcification and the individual contribution to progressive extracellular matrix stiffening require further clarification. Specifically, we discuss (1) the valvular biomechanics and layered ECM composition, (2) patterns in the cellular contribution, temporal onset, and risk factors for valvular fibrosis, (3) imaging valvular fibrosis, (4) biomechanical implications of valvular fibrosis, and (5) molecular mechanisms promoting fibrotic tissue remodeling and the possibility of reverse remodeling. This review explores our current understanding of the cellular and molecular drivers of fibrogenesis and the pathophysiological role of fibrosis in CAVD.
View
... Cao and Sucosky. [13] found that abnormal shear stress seems to trigger pathological cascades which may lead to aortic valve calci cation ultimately. Partho and Narula. ...
Assessment of Cardiac Function by Wall Shear Stress Using Vector Flow Mapping in the Patients with Dilated Cardiomyopathy
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  • Mar 2021
The purpose of this study was to assess the applications of wall shear stress (WSS) of left ventricle (LV) using vector flow mapping (VFM) in the patients with dilated cardiomyopathy (DCM). Compared with controls, WSS at basal and middle segments of ventricular septum and middle segment of left ventricular lateral wall were significantly decreased during RE in DCM patients. And during RF, the WSS in all segments of LV were significantly decreased in the DCM patients (all P < 0.05). In controls, in every phase, WSS gradually decreased from the basal to the middle and apical segment both in ventricular septum and left ventricular lateral wall.And in every segment, the WSS from isovolumic contraction to the peak of rapid ejection period or isovolumic relaxation to the peak of rapid filling period all presented the trend of increased,meanwhile the WSS from the peak of rapid ejection to isovolumic relaxation period or the peak of rapid filling to the peak of atrial contraction period all showed a decreasing trend (all P < 0.05). However, these regularities were not observed in DCM patients. There were obvious differences of WSS derived from VFM between DCM patients and controls. In conclusion, WSS may be recognized as a new indicator for detecting abnormal cardiac function in DCM patients.
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... However, interestingly, several studies have independently shown that spatial (as opposed to temporal) variations in the distribution of blood pressure on the valve components have a minimal influence on the AV dynamics (Howard et al., 2003;Soncini et al., 2009;Koch et al., 2010;Labrosse et al., 2010). Of course, FSI is indispensable if one is after the coupling between the mitral valve, the left ventricle, and the AV (Mao et al., 2017) or if one is interested in determining the shear stresses on the AV cusps (Cao and Sucosky, 2017). However, dry models (i.e., pressure-driven only; no fluids) can be valuable tools to assess native AV cusps kinematics and stresses and to simulate AV surgical procedures; however, it has been argued that they might not be the best choice for prosthetic valves (Luraghi et al., 2017). ...
View
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Full-text available
  • May 2023
Tissue-engineered heart valves (TEHVs) are emerging alternatives to current valve prostheses and prospectively a lifelong replacement. Calcification, a pathological complication for biological protheses, has been reported in preclinical TEHV studies. Systematic analysis of its occurrence is missing. This review aims to: 1) systematically review reported calcification of pulmonary TEHVs in large-animal studies; and 2) analyze the influence of engineering methodology (choice of scaffold material, cell preseeding) and animal model (animal species and age) on calcification. Baseline analysis included 80 studies, of which 41 studies containing 108 experimental groups were included in meta-analysis. Inclusion was low because only 55% of studies reported on calcification. Meta-analysis showed an overall average calcification event rate of 35% (95% CI: 28%-43%). Calcification was more prominent (P = 0.023) in the arterial conduit region (34%; 95% CI: 26%-43%) than in the valve leaflets (21%; 95% CI: 17%-27%), and was mostly (42% in leaflets, 60% in conduits) present in a mild form. Time-analysis showed an initial surge within 1 month after implantation, decreased calcification between 1 and 3 months, and then progression over time. There were no significant differences in degree of calcification between TEHV strategy nor animal models. Much variability between individual studies was observed in degree of calcification as well as quality of analysis and reporting thereof, hampering adequate comparisons between studies. These findings underline the need for improved analysis and better reporting standards of calcification in TEHVs. It also necessitates control-based research to further enlighten the risk of calcification for tissue-engineered transplants compared to current options. This can bring the field of heart valve tissue engineering forward toward safe clinical use.
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Semi-Automated Construction of Patient-Specific Aortic Valves from Computed Tomography Images
Article
  • Oct 2022
This paper presents a semi-automatic method for the construction of volumetric models of the aortic valve using computed tomography angiography images. Although the aortic valve typically cannot be segmented directly from a computed tomography angiography image, the method described herein uses manually selected samples of an aortic segmentation derived from this image to inform the construction. These samples capture certain physiologic landmarks and are used to construct a volumetric valve model. As a demonstration of the capabilities of this method, valve models for 25 pediatric patients are created. A selected valve anatomy is used to perform fluid–structure interaction simulations using the immersed finite element/difference method with physiologic driving and loading conditions. Simulation results demonstrate this method creates a functional valve that opens and closes normally and generates pressure and flow waveforms that are similar to those observed clinically.
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Computational Comparison of Regional Stress and Deformation Characteristics in Tricuspid and Bicuspid Aortic Valve Leaflets
Article
Full-text available
  • Apr 2016
The bicuspid aortic valve (BAV) is the most common congenital valvular defect and a major risk factor for secondary calcific aortic valve disease (CAVD). While hemodynamics is presumed to be a potential contributor to this complication, the validation of this theory has been hampered by the limited knowledge of the mechanical stress abnormalities experienced by BAV leaflets and their dependence on the heterogeneous BAV fusion patterns. The objective of this study was to compare computationally the regional and temporal fluid wall shear stress (WSS) and structural deformation characteristics in TAV, type-0 and type-I BAV leaflets. Arbitrary Lagrangian Eulerian fluid-structure interaction models were designed to simulate the flow and leaflet dynamics in idealized TAV, type-0 and type-I BAV geometries subjected to physiologic transvalvular pressure. The regional leaflet mechanics was quantified in terms of temporal shear magnitude (TSM), oscillatory shear index (OSI), temporal shear gradient (TSG) and principal stretch. The simulations identified regions of WSS overloads and increased WSS bidirectionality (174% increase in TSM, 0.10 increase in OSI on type-0 leaflets) in BAV leaflets relative to TAV leaflets. BAV leaflets also experienced larger radial deformations than TAV leaflets (4% increase in type-0 BAV leaflets). Type-I BAV leaflets exhibited contrasted WSS environments marked by WSS overloads on the non-coronary leaflet and sub-physiologic WSS levels on the fused leaflet. This study provides important insights into the mechanical characteristics of BAV leaflets, which may further our understanding of the role played by hemodynamic forces in BAV disease.
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Comparative hemodynamics in an aorta with bicuspid and trileaflet valves
Article
Full-text available
  • Apr 2016
  • THEOR COMP FLUID DYN
Bicuspid aortic valve (BAV) is a congenital heart defect that has been associated with serious aortopathies, such as aortic stenosis, aortic regurgitation, infective endocarditis, aortic dissection, calcific aortic valve and dilatation of ascending aorta. There are two main hypotheses to explain the increase prevalence of aortopathies in patients with BAV: the genetic and the hemodynamic. In this study, we seek to investigate the possible role of hemodynamic factors as causes of BAV-associated aortopathy. We employ the curvilinear immersed boundary method coupled with an efficient thin-shell finite-element formulation for tissues to carry out fluid–structure interaction simulations of a healthy trileaflet aortic valve (TAV) and a BAV placed in the same anatomic aorta. The computed results reveal major differences between the TAV and BAV flow patterns. These include: the dynamics of the aortic valve vortex ring formation and break up; the large-scale flow patterns in the ascending aorta; the shear stress magnitude, directions, and dynamics on the heart valve surfaces. The computed results are in qualitative agreement with in vivo magnetic resonance imaging data and suggest that the linkages between BAV aortopathy and hemodynamics deserve further investigation.
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Three-Dimensional Macro-Scale Assessment of Regional and Temporal Wall Shear Stress Characteristics on Aortic Valve Leaflets
Article
Full-text available
  • May 2015
The aortic valve (AV) achieves unidirectional blood flow between the left ventricle and the aorta. Although hemodynamic stresses have been shown to regulate valvular biology, the native wall shear stress (WSS) experienced by AV leaflets remains largely unknown. The objective of this study was to quantify computationally the macro-scale leaflet WSS environment using fluid-structure interaction modeling. An arbitrary Lagrangian-Eulerian approach was implemented to predict valvular flow and leaflet dynamics in a three-dimensional AV geometry subjected to physiologic transvalvular pressure. Local WSS characteristics were quantified in terms of temporal shear magnitude (TSM), oscillatory shear index (OSI) and temporal shear gradient (TSG). The dominant radial WSS predicted on the leaflets exhibited high amplitude and unidirectionality on the ventricularis (TSM > 7.50 dyn/cm2, OSI < 0.17, TSG > 325.54 dyn/cm2•s) but low amplitude and bidirectionality on the fibrosa (TSM < 2.73 dyn/cm2, OSI > 0.38, TSG < 191.17 dyn/cm2•s). The radial WSS component computed in the leaflet base, belly and tip demonstrated strong regional variability (ventricularis TSM: 7.50–22.32 dyn/cm2, fibrosa TSM: 1.26–2.73 dyn/cm2). While the circumferential WSS exhibited similar spatially dependent magnitude (ventricularis TSM: 1.41–3.40 dyn/cm2, fibrosa TSM: 0.42–0.76 dyn/cm2) and side-specific amplitude (ventricularis TSG: 101.73–184.43 dyn/cm2•s, fibrosa TSG: 41.92–54.10 dyn/cm2•s), its temporal variations were consistently bidirectional (OSI > 0.25). This study provides new insights into the role played by leaflet-blood flow interactions in valvular function and critical hemodynamic stress data for the assessment of the hemodynamic theory of AV disease.
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Bone Morphogenetic Protein-4 and Transforming Growth Factor-Beta1 in Acute Valvular Response to Supra-Physiologic Hemodynamic Stresses
Article
Full-text available
  • Jun 2015
  • World J Cardiol
AIM: To explore ex vivo the role of BMP-4 and TGF-β1 in acute valvular response to fluid shear stress (FSS) abnormalities. METHODS: Porcine valve leaflets were subjected ex vivo to physiologic FSS, supra-physiologic FSS magnitude at normal frequency and supra-physiologic FSS frequency at normal magnitude for 48 hours in a double-sided cone-and-plate bioreactor filled with standard culture medium. The role of BMP-4 and TGF-β1 in the valvular response was investigated by promoting or inhibiting the downstream action of those cytokines via culture medium supplementation with BMP-4 or the BMP antagonist noggin, and TGF-β1 or the TGF-β1 inhibitor SB-431542, respectively. Fresh porcine leaflets were used as controls. Each experimental group consisted of six leaflet samples. Immunostaining and immunoblotting were performed to assess endothelial activation in terms of ICAM-1 and VCAM-1 expressions, paracrine signaling in terms of BMP-4 and TGF-β1 expressions and extracellular matrix (ECM) remodeling in terms of cathepsin L, cathepsin S, MMP-2 and MMP-9 expressions. Immunostained images were quantified by normalizing the intensities of positively stained regions by the number of cells in each image while immunoblots were quantified by densitometry. RESULTS: Regardless of the culture medium, physiologic FSS maintained valvular homeostasis. Tissue exposure to supra-physiologic FSS magnitude in standard medium stimulated paracrine signaling (TGF-β1: 467 ± 22% vs 100 ± 6% in fresh controls, BMP-4: 258 ± 22% vs 100 ± 4% in fresh controls; P < 0.05) and ECM degradation (MMP-2: 941 ± 90% vs 100 ± 19% in fresh controls, MMP-9: 1219 ± 190% vs 100 ± 16% in fresh controls, cathepsin L: 1187 ± 175% vs 100 ± 12% in fresh controls, cathepsin S: 603 ± 88% vs 100 ± 13% in fresh controls; P < 0.05), while BMP-4 supplementation also promoted fibrosa activation and TGF-β1 inhibition reduced MMP-9 expression to the native tissue level (MMP-9: 308 ± 153% with TGF-β1 inhibition vs 100 ± 16% in fresh control; P > 0.05). Supra-physiologic FSS frequency had no effect on endothelial activation and paracrine signaling regardless of the culture medium but TGF-β1 silencing attenuated FSS-induced ECM degradation via MMP-9 downregulation (MMP-9: 302 ± 182% vs 100 ± 42% in fresh controls; P > 0.05). CONCLUSION: Valvular tissue is sensitive to FSS abnormalities. The TGF-β1 inhibitor SB-431542 is a potential candidate molecule for attenuating the effects of FSS abnormalities on valvular remodeling.
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Effect of Bicuspid Aortic Valve Cusp Fusion on Aorta Wall Shear Stress: Preliminary Computational Assessment and Implication for Aortic Dilation
Article
Full-text available
  • May 2015
The bicuspid aortic valve (BAV) is a major congenital valvular abnormality and is associated with a high prevalence of aortic dilation, whose expression depends on the type of leaflet fusion. Although BAV hemodynamics is considered a potential pathogenic contributor, the impact of BAV fusion on ascending aorta (AA) wall shear stress (WSS) remains largely unknown. A fluid-structure interaction approach was implemented to predict the hemodynamics and WSS characteristics in realistic AA models subjected to the flow of a normal tricuspid aortic valve (TAV) and three BAV morphotypes (left-right-coronary cusp fusion (LR), right-non coronary cusp fusion (RN) and non-left coronary cusp fusion (NL)). TAV flow conditions subjected the proximal and middle AA to a streamlined flow typical of flows in bends, while BAV flow conditions generated increased flow helicity. The LR-BAV orifice jet generated flow abnormalities primarily in the proximal AA, which were marked by a uniform WSS overload along the wall circumference and contrasted WSS directionalities on the wall convexity and concavity. Flow abnormalities generated by the RN-BAV and NL-BAV inlet flow conditions were more diffuse and consisted of WSS overloads in the convexity of the proximal and middle AA and contrasted WSS directionalities in the anterior and posterior wall regions. This study demonstrates the impact of the BAV morphotype on AA hemodynamics and provides quantitative evidence for the existence of WSS abnormalities in aortic wall regions prone to dilation.
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Fluid–structure interaction analysis of the left coronary artery with variable angulation
Article
Full-text available
  • Jun 2014
The aim of this study is to elucidate the correlation between coronary artery branch angulation, local mechanical and haemodynamic forces at the vicinity of bifurcation. Using a coupled fluid-structure interaction (FSI) modelling approach, five idealized left coronary artery models with various angles ranging from 70° to 110° were developed to investigate the influence of branch angulations. In addition, one CT image-based model was reconstructed to further demonstrate the medical application potential of the proposed FSI coupling method. The results show that the angulation strongly alters its mechanical stress distribution, and the instantaneous wall shear stress distributions are substantially moderated by the arterial wall compliance. As high tensile stress is hypothesized to cause stenosis, the left circumflex side bifurcation shoulder is indicated to induce atherosclerotic changes with a high tendency for wide-angled models.
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Defining the Role of Fluid Shear Stress in the Expression of Early Signaling Markers for Calcific Aortic Valve Disease
Article
Full-text available
Calcific aortic valve disease (CAVD) is an active process presumably triggered by interplays between cardiovascular risk factors, molecular signaling networks and hemodynamic cues. While earlier studies demonstrated that alterations in fluid shear stress (FSS) on the fibrosa could trigger inflammation, the mechanisms of CAVD pathogenesis secondary to side-specific FSS abnormalities are poorly understood. This knowledge could be critical to the elucidation of key CAVD risk factors such as congenital valve defects, aging and hypertension, which are known to generate FSS disturbances. The objective of this study was to characterize ex vivo the contribution of isolated and combined abnormalities in FSS magnitude and frequency to early valvular pathogenesis. The ventricularis and fibrosa of porcine aortic valve leaflets were exposed simultaneously to different combinations of sub-physiologic/physiologic/supra-physiologic levels of FSS magnitude and frequency for 24, 48 and 72 hours in a double cone-and-plate device. Endothelial activation and paracrine signaling were investigated by measuring cell-adhesion molecule (ICAM-1, VCAM-1) and cytokine (BMP-4, TGF-β1) expressions, respectively. Extracellular matrix (ECM) degradation was characterized by measuring the expression and activity of the proteases MMP-2, MMP-9, cathepsin L and cathepsin S. The effect of the FSS treatment yielding the most significant pathological response was examined over a 72-hour period to characterize the time-dependence of FSS mechano-transduction. While cytokine expression was stimulated under elevated FSS magnitude at normal frequency, ECM degradation was stimulated under both elevated FSS magnitude at normal frequency and physiologic FSS magnitude at abnormal frequency. In contrast, combined FSS magnitude and frequency abnormalities essentially maintained valvular homeostasis. The pathological response under supra-physiologic FSS magnitude peaked at 48 hours but was then maintained until the 72-hour time point. This study confirms the sensitivity of valve leaflets to both FSS magnitude and frequency and suggests the ability of supra-physiologic FSS levels or abnormal FSS frequencies to initiate CAVD mechanisms.
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Ex Vivo Evidence for the Contribution of Hemodynamic Shear Stress Abnormalities to the Early Pathogenesis of Calcific Bicuspid Aortic Valve Disease
Article
Full-text available
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.
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Role of Pathologic Shear Stress Alterations in Aortic Valve Endothelial Activation
Article
Full-text available
  • Mar 2010
Calcific aortic stenosis is the most common aortic valve (AV) disease and is triggered by an active inflammatory process involving endothelial activation and cytokine expression. Interfacing between the leaflet and the surrounding blood flow, shear stress is presumed to play an important role in endothelial injury. This study investigated the hypothesis that pathologic alterations in shear stress magnitude contribute to valvular endothelial activation via BMP-4- and TGF-β1-dependent mechanisms. The fibrosa of porcine AV leaflets was subjected to physiologic, sub-physiologic and supra-physiologic magnitudes of native oscillatory shear stress for 48h. Endothelial activation was assessed via immunohistochemistry in terms of ICAM-1 and VCAM-1 expressions. Cytokine expression was investigated in terms of BMP-4 and TGF-β1. Pro- and anti-osteogenic media were used to characterize the role of those cytokines in the shear stress-induced pathological response. Supra-physiologic shear stress increased the expression of all biomarkers in a shear stress magnitude-dependent manner. In contrast, neither physiologic nor sub-physiologic shear stress elicited a pro-inflammatory response. While BMP-4 inhibition and supplementation had limited effects on endothelial activation, TGF-β1 supplementation increased the overall leaflet pro-inflammatory state and TGF-β1 inhibition reduced endothelial activation in response to elevated shear stress. Combined TGF-β1 and BMP-4 inhibition completely suppressed shear stress-induced endothelial activation. The results demonstrate that elevated shear stress activates the valvular endothelium on the fibrosa via a BMP-4- and TGF-β1-dependent pathway. The suggested synergy between those cytokines also provides new insights into the transduction of valvular hemodynamic alterations into a pathological response. KeywordsAortic valve-Endothelial activation-Shear stress-Cytokines-Adhesion molecules
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Coronary Flow Impacts Aortic Leaflet Mechanics and Aortic Sinus Hemodynamics
Article
  • Jan 2015
Mechanical stresses on aortic valve leaflets are well-known mediators for initiating processes leading to calcific aortic valve disease. Given that non-coronary leaflets calcify first, it may be hypothesized that coronary flow originating from the ostia significantly influences aortic leaflet mechanics and sinus hemodynamics. High resolution time-resolved particle image velocimetry (PIV) measurements were conducted to map the spatiotemporal characteristics of aortic sinus blood flow and leaflet motion with and without physiological coronary flow in a well-controlled in vitro setup. The in vitro setup consists of a porcine aortic valve mounted in a physiological aorta sinus chamber with dynamically controlled coronary resistance to emulate physiological coronary flow. Results were analyzed using qualitative streak plots illustrating the spatiotemporal complexity of blood flow patterns, and quantitative velocity vector and shear stress contour plots to show differences in the mechanical environments between the coronary and non-coronary sinuses. It is shown that the presence of coronary flow pulls the classical sinus vorticity deeper into the sinus and increases flow velocity near the leaflet base. This creates a beneficial increase in shear stress and washout near the leaflet that is not seen in the non-coronary sinus. Further, leaflet opens approximately 10% farther into the sinus with coronary flow case indicating superior valve opening area. The presence of coronary flow significantly improves leaflet mechanics and sinus hemodynamics in a manner that would reduce low wall shear stress conditions while improving washout at the base of the leaflet.
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