Fluid Mechanics of Heart Valves and Their Replacements

FL48CH10-Sotiropoulos ARI 25 August 2015 14:11
Review in Advance first posted online

V I E W
E on September 2, 2015. (Changes may
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still occur before final publication
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online and in print.)
C E
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A
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Fluid Mechanics of Heart

Valves and Their Replacements
Fotis Sotiropoulos,1,2 Trung Bao Le,2
Access provided by University of South Dakota on 09/04/15. For personal use only.
and Anvar Gilmanov2

Annu. Rev. Fluid Mech. 2016.48. Downloaded from www.annualreviews.org
1
Department of Civil, Environmental, and Geo-Engineering, University of Minnesota,
Minneapolis, Minnesota 55455; email: fotis@umn.edu
2
Saint Anthony Falls Laboratory, College of Science and Engineering, University of Minnesota,
Minneapolis, Minnesota 55414
Annu. Rev. Fluid Mech. 2016. 48:259–83 Keywords

The Annual Review of Fluid Mechanics is online at aortic valve, mitral valve, left ventricle, hemodynamics, vortex ring
fluid.annualreviews.org
This article’s doi: Abstract

10.1146/annurev-fluid-122414-034314
As the pulsatile cardiac blood flow drives the heart valve leaflets to open and
Copyright c 2016 by Annual Reviews. close, the flow in the vicinity of the valve resembles a pulsed jet through
All rights reserved
a nonaxisymmetric orifice with a dynamically changing area. As a result,
three-dimensional vortex rings with intricate topology emerge that interact
with the complex cardiac anatomy and give rise to shear layers, regions of
recirculation, and flow instabilities that could ultimately lead to transition
to turbulence. Such complex flow patterns, which are inherently valve- and
patient-specific, lead to mechanical forces at scales that can cause blood
cell damage and thrombosis, increasing the likelihood of stroke, and can
trigger the pathogenesis of various life-threatening valvular heart diseases.
We summarize the current understanding of flow phenomena induced by
heart valves, discuss their linkage with disease pathways, and emphasize the
research advances required to translate in-depth understanding of valvular
hemodynamics into effective patient therapies.
259
Changes may still occur before final publication online and in print
1. INTRODUCTION
Heart valves help maintain unidirectional blood flow through the heart (see Figure 1a). They are
complex biological structures (Chester et al. 2014) that have evolved to passively deform a few
billion cycles during their lifetime and be incredibly durable and highly efficient devices (Forouhar
Anatomy of the human heart The heart cycle

Isovolumic Isovolumic
a b contraction relaxation
Myocardial
Pressure (mm Hg)

contraction Systolic pressure
120 Atrial
Right atrium contraction
Ascending
aorta 90 Aortic pressure Diastolic
pressure
Sinus 60
5 Left atrium Left ventricle pressure

30
1
2 Aortic valve
Aortic valve closed open
Volume flow rate (mL/s)
3 500
Mitral valve open Mitral valve
4 closed
E-wave A-wave
250
–250
Right ventricle Left ventricle –500
The aortic valve, closed and open d Bileaflet mechanical e Bioprosthetic

heart valve heart valve
c (St. Jude Medical Regent) (Medtronic Hancock II)
Hinge region Commissure
Figure 1
Cardiac anatomy and native and prosthetic heart valves. (a) Major anatomic features of the heart, including most of the native valves
and their supporting structures, identified inside a dissected diseased human heart. The blue arrow indicates the main flow direction
during a cardiac cycle. Shown are the mitral annulus, mitral valve leaflets, chordae tendinae, posterior papillary muscles,
and aortic valve. (b) The heart cycle shown in terms of time series of intraventricular pressure and volume flow rate. (c) The native
aortic valve shown at two instants during the cardiac cycle (closed and fully open positions). Images in panel c courtesy of the University
of Minnesota/ c Medtronic Inc. For clarity some labels were digitally removed from these two images. (d,e) Representative replacement
valves, including (d ) a mechanical bileaflet heart valve (St. Jude Medical Regent) and (e) a bioprosthetic trifleaflet valve with compliant
leaflets (Medtronic Hancock II). Panels a–c reproduced with permission from the Visible Heart Lab (Dr. Paul Iazzio, University of
Minnesota). More such images can be found in the University of Minnesota Atlas of Human Cardiac Anatomy (http://www.vhlab.
umn.edu/atlas/). Panels d and e taken from Kheradvar et al. (2015) and reproduced with permission from Springer.
260 Sotiropoulos · ·
Le Gilmanov
et al. 2006). As a result of the flow-structure interaction (FSI) between the pulsatile blood flow
and valve leaflets, the valves experience continuous loading through the cardiac cycle, including
Tissue remodeling:
compression, stretching, and bending stresses (Sacks et al. 2009a). The arising mechanical stresses
the structural
act on the endothelial cells lining the valve leaflets and, along with genetic and other environmental reorganization of
factors, can trigger complex biochemical processes that could ultimately lead to tissue remodeling, tissue, which can cause
calcification, and stenosis (Sacks et al. 2009a). Genetic and environmental factors can lead to the stiffening of heart
congenital malformation of the aortic valve leaflets, bicuspid aortic valve (BAV) disease, giving rise valve leaflets
to altered hemodynamics in the ascending aorta, which are believed to be linked with diseases such Calcification: the
as ascending aortic dilation (Barker & Markl 2011). Common therapies for valvular diseases include process of [Ca2+ ] ion
deposit on the valve
valve repair or replacement with prosthetic heart valves (PHVs). There are various types of valve
leaflets, which changes
prostheses available in the market, including mechanical and tissue-engineered or bioprosthetic the mechanical
heart valves (Yoganathan et al. 2005). properties of the tissue
This review focuses on the fluid mechanics of the native mitral and aortic valves on the left Stenosis: the
side of the heart, as they are the most common to develop diseases (Roger et al. 2012), and reduction in the ability
their prosthetic replacements. For the sake of completeness, we also include relevant information of a heart valve to
related to heart valve anatomy, mechanobiology, and pathology. Such discussion, however, is open fully
restricted to issues that are relevant to valvular fluid mechanics phenomena. For a more in-depth Bicuspid aortic valve
understanding of heart valve structure and pathology, the reader is referred to Sacks et al. (2009a,b) (BAV): the most
common congenital
and Hinton & Yutzey (2011). We also encourage readers to examine earlier reviews on heart valve
disease in which two of
fluid mechanics (Peskin 1982, Yoganathan et al. 2004) to gauge progress in this rapidly expanding the three aortic leaflets
field of knowledge. are fused together
during valvulogenesis
LA: left atrium
2. ANATOMY AND FUNCTIONALITY OF THE MITRAL
LV: left ventricle
AND AORTIC VALVES
MV: mitral valve
Oxygenated blood from the lungs enters the left heart through the pulmonary artery into the
AV: aortic valve
left atrium (LA). The diastolic phase of the cardiac cycle starts as the left ventricle (LV) relaxes,
causing the mitral valve (MV) to open (E-wave) and blood to rapidly fill the LV chamber (see Isovolumic
relaxation and
Figures 1b and 2). Subsequently, the LV exhibits a short period of equilibrium state (diastasis)
contraction: the
before it expands further under the atrioventricular pressure gradient from the LA contraction relaxation/contraction
(A-wave; atrial contraction) to allow remaining blood in the LA to enter the LV. As shown of the left ventricle
in Figure 1b, the aortic pressure is much higher than the LV pressure throughout diastole. while both the aortic
Therefore, the aortic valve (AV) is fully closed during diastole. The diastole ends when the LV and mitral valves are
closed; the left
transitions to isovolumic contraction, which drives the MV to fully close. The systole starts as the
ventricular pressure
LV begins to actively contract (myocardial contraction), which forces the AV to open and push decreases/increases
blood into the cardiovascular system through the aorta. The rate of LV contraction begins to sharply without any
decrease during the decelerating phase of systole, reversing the direction of the pressure gradient changes in the left
acting on the AV leaflets and ultimately causing the AV to close before isovolumic relaxation. ventricular volume
The role of the two valves is critical throughout the cardiac cycle as they ensure the unidirec- Ion channels:
tionality of blood flow from the lungs to the aorta (Sacks et al. 2009a). Both valves are passive pore-forming
membrane proteins
structures that respond to dynamic pressure gradients driven by the contractions of the heart walls,
that regulate the
which originate via the complex and inherently multiscale coupling of chemical (ion channels), permeability of a
electrical (transmembrane potential), and mechanical (mechanical stresses) processes (see Wong cellular membrane to
et al. 2011 for details). The response of the valve leaflets depends on the details of the valve ions
anatomy and tissue properties and the dynamic motion of the heart walls, thus giving rise to a
coupled, multiscale and multiphysics FSI problem (Sacks et al. 2009a, Weinberg et al. 2010).
The MV is an intricate structure consisting of four subvalvular components (Quill et al. 2009)
(see Figure 1a): the mitral annulus, the anterior and posterior leaflets, the chordae tendineae,
www.annualreviews.org • Fluid Mechanics of Heart Valves 261
Figure 2
Simulation of blood flow in a generic whole heart with its four valves using the immersed boundary method
of McQueen & Peskin (2000). The valve and heart walls are modeled as a network of inextensible fibers that
interact with flow. The instance shown corresponds to the opening period of the mitral valve when
oxygenated blood flow (red vectors) from the left atrium enters the left ventricle, forming the mitral vortex
ring. Image courtesy of Charles S. Peskin and David M. McQueen, New York University, New York, NY.
and the two papillary muscles. The mitral annulus, which supports the upper portion of the MV
apparatus, separates the atrial myocardium from the valve leaflets. The mitral annulus generally
has a saddle-shaped geometry and dynamically changes its shape during the cardiac cycle in a non-
planar fashion (Rausch et al. 2011). The anterior and posterior leaflets are connected together via
connective tissues (anterolateral and posteromedial commissures), as shown in Figure 1a. Below
the commissures, there are two respective papillary muscles: the anterolateral and posteromedial
Multiscale and papillary muscles. The papillary muscles are connected to the leaflets via the chordae tendineae.
multiphysics
During systole, the papillary muscles actively contract to generate a force, which is transmitted
fluid-structure
interaction (FSI): via the chordae tendineae (Askov et al. 2013). This force keeps the valve closed and prevents
the relationship retrograde flow from entering the LA. During early diastole, the force transmitted through the
between chemical papillary muscles acts to facilitate the opening of the MV until mid-diastole. For more details on
potentials at the MV mechanics, the reader is referred to Sun et al. (2014).
cellular level, electrical
In comparison to the MV, the AV has a much simpler structure, as seen in Figure 1c. It consists
currents in the heart,
mechanical forces on of three semilunar leaflets (right, left, noncoronary), which are thin cusps attached to the aortic
heart walls, and blood root at the three sinuses of Valsalva in the aorta. In a healthy valve, the three leaflets coapt fully
flow forces on valve during diastole to hemodynamically separate the ascending aorta and the LV.
leaflets The tissue of the leaflets is characterized by a multilayer structure both for the aortic valve
(ventricularis, brosa, and spongiosa) (Sacks et al. 2009a) and for the mitral valve (atrialis/spongiosa,
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brosa, and ventricularis) (Rabbah et al. 2013). Furthermore, for both valve leaflets, collagen fibers
are found to be preferentially oriented in the circumferential directions, leading to anisotropic
mechanical response. Conversely, the mitral chordae consist of collagen fibers aligned along their
Aortic root
length and have been shown to exhibit viscoelastic behavior during tensile tests (Rabbah et al. dilatation/aneurysm:
2013). More details can be found in Rabbah et al. (2013) and Sun et al. (2014). disease in which the
Major advances in imaging technologies, such as real-time three-dimensional (3D) echocar- natural aortic root is
diography (Veronesi et al. 2008), multislice computed tomography (Wang & Sun 2013), and altered, limiting the
normal function of the
cardiac magnetic resonance (Stevanella et al. 2011), presently allow the anatomy of heart valves
aortic valve
to be obtained for individuals with great accuracy. Such data can be used as input for developing
Regurgitation: the
patient-specific FSI models of heart valves (Sotiropoulos & Borazjani 2009, Votta et al. 2013).
backward (leakage)
flow of blood through
a defective heart valve
3. HEMODYNAMICS AND VALVULAR HEART DISEASE
Coaptation: process
There are two types of heart valve diseases: congenital and acquired. The most common congenital in which three leaflets
one is BAV disease, which occurs in 1–2% of the general population (Braverman et al. 2005). come into contact to
Acquired diseases result from environmental and diet or lifestyle factors that progress over a ensure the full closure
of the valve
long period of time. Common acquired valve diseases include aortic root dilatation, aortic root
aneurysm, valve calcification, aortic and mitral stenosis, and regurgitation. Such diseases inhibit Wall shear stress
(WSS): thought to be
the functionalities of the valve by reducing coaptation (regurgitation), reducing the valve effective
an important stimulus
opening area (stenosis), or increasing the complexity of the valve jet flow and impacting its ensuing regulating the growth
interaction with the arterial wall. Blood flow–induced mechanical forces could stimulate long-term of endothelial cells on
adaption and remodeling of the heart valve structure or vessel walls (Sacks et al. 2009a) and could the valvular surfaces
become a contributing factor to disease. In fact, it has long been hypothesized that a number of
valvular diseases may be linked to hemodynamic factors (Gould et al. 2013). AV calcification, for
instance, has been associated with the complex spatial structure and rich dynamics of the wall shear
stress (WSS) field on the aortic side of the leaflets (Ge & Sotiropoulos 2010, Simmons et al. 2005).
It is common for BAV patients to have a higher chance of developing aortic dilatation, which has
been linked to irregular hemodynamics induced by the altered AV shape (Barker & Markl 2011).
There is also a growing body of evidence pointing to the connection between valvular diseases and
LV dysfunction pathogenesis (Grande-Allen et al. 2005). Heart remodeling (Chaput et al. 2008)
or failure (Grande-Allen et al. 2005) could lead to the stiffening of the valve leaflets, thus impacting
the ability of the leaflets to open and close and altering the valve-induced hemodynamics. Other
conditions such as aortic root diseases may also severely alter the functionality of aortic leaflets
(Calleja et al. 2013). The connection between valvular, aortic, and ventricular diseases coupled with
the anatomic complexities of the heart underscores the need to study heart valve hemodynamics
and its relationship to heart disease in a patient-specific manner within the left heart anatomic
environment in which the valves operate (Votta et al. 2013).
4. FUNDAMENTALS OF PULSATILE BLOOD FLOW IN THE HEART

Blood is a complex fluid mostly consisting of red blood cells, white blood cells, platelets, and
plasma. The typical size of blood cells is of the order of 10 μm. For a comprehensive review of
blood properties and modern approaches for simulating blood flow phenomena at cellular scales,
the reader is referred to Sotiropoulos et al. (2011) and Freund (2014). The size of the heart and
surrounding blood vessels is larger by at least three orders of magnitude than the typical blood cell.
Therefore, when considering flow phenomena associated with heart valves, one can treat blood,
for the most part, as a continuum medium that is incompressible and Newtonian (Ku 1997). The
governing equations of blood flow are the incompressible, unsteady Navier-Stokes equations and
the continuity equation (Peskin 1982) with nominal kinematic viscosity ν ≈ 4 × 10−6 m2 /s (Ku
1997).
The beating heart induces a pulsatile flow, and the relevant nondimensional numbers that
appear in the nondimensional governing equations are the Reynolds number and the Womersley
number. The Reynolds number is defined as
U max D
Re = , (1)
ν
which quantifies the ratio of inertial to viscous forces. The Womersley number is defined as

D 2π
α= , (2)
2 Tν
which quantifies the relative magnitude of transient inertial forces to the viscous forces. In these
equations, Umax , D, and T are the appropriate velocity, length, and timescale. For a healthy adult
heart, a representative velocity scale can be derived from the peak velocity of blood flow, which
is of the order of U = 1 m/s (Kilner et al. 1993, Yoganathan et al. 2004) and could reach as high
as 4 m/s in patients with valvular diseases (Saikrishnan et al. 2012). The length scale can be chosen
as the diameter of the MV or AV, which is of the order of D = 2–3 cm. Finally, the cyclic timescale
that governs the large-scale hemodynamic processes is defined by the normal heart rate at rest (T ),
which is typically in the range of 60–80 beats per minute (Ku 1997). Using these scales, the values
of Re and α can be estimated to be of the order of Re ≈ 6,000 and α ≈ 19. For such values of peak
Re, the intraventricular flow should be expected to undergo periodic transition to turbulence (Ku
1997).
Because of the turbulent nature of valvular flows, the Reynolds decomposition approach has
been widely used in the literature to describe the state of blood flow induced by valves and
to quantify hemodynamic forces due to turbulence (Yoganathan et al. 2004). The instantaneous
blood flow velocity u at every instant of the cardiac cycle is decomposed into an ensemble-averaged
component for that instant in the cycle U (obtained by averaging several realizations of phase-
locked data) and a component u fluctuating about the ensemble-averaged value (Ge et al. 2008). By
applying this averaging procedure to the governing equations, we obtain the unsteady Reynolds-
averaged Navier-Stokes equations, which contain the Reynolds stress tensor:
Ri j = −ρui u j , (3)
where ρ ≈ 1,050 kg/m3 is the density of blood. The components of the Reynolds stress tensor have
a dimension of force per unit area and are often used in the heart valve literature to characterize
the state of turbulence. For example, Hwang et al. (1977) reported that MV flow transitions to
turbulence with the peak Reynolds stresses at approximately 150 dyn/cm2 .
The Reynolds stress tensor is the artifact of a specific averaging process and does not represent
a real physical force experienced by blood cells (see the sidebar, The Triple Decomposition).
Therefore, it should be viewed with great care when assessing blood damage potential (Ge et al.
2008). The scales at which heart valve flows dissipate energy into heat (i.e., the Kolmogorov length
scale and timescale η and τ η , respectively) have been estimated by several authors to be in the range
of η ≈ 50 μm and τη ≈ 700 μs (Ge et al. 2008, De Tullio et al. 2009, Sotiropoulos et al. 2011, Yun
et al. 2014b). These estimates underscore the challenges for both experimental and computational
studies seeking to quantify valvular hemodynamics. For example, for direct numerical simulations
or large-eddy simulations of physiologic pulsatile flow, these estimates provide guidelines for the
required spatial and temporal resolution (De Tullio et al. 2009).
Early approaches to studying valvular hemodynamics employ integral quantities such as the
flow rate Q(t) through the valve, its temporal variation dQ/dt, the valve effective opening area
Le Gilmanov
THE TRIPLE DECOMPOSITION
An important characteristic of heart valve flows is that they are dominated by large-scale, cycle-to-cycle variations.
Such variations are over and above random fluctuations due to turbulence and arise from, for example, variations
in the cardiac cycle, cycle-to-cycle variations of valve leaflet kinematics, and large-scale organized coherent vortex
shedding from valve leaflets (Ge et al. 2008). The standard Reynolds decomposition cannot quantify the contribu-
tions of cycle-to-cycle variations as all fluctuations about the mean are lumped together into a single fluctuating
component u . An alternative that seeks to separate the contributions to the Reynolds stresses of fluctuations due
to turbulence from those due to cycle-to-cycle variations is the triple decomposition (Reynolds & Hussain 1972,
Tiederman et al. 1988):
u = U + ũ + u ,
where ũ is the cycle-to-cycle variation, and u is the fluctuation due to turbulence (Reynolds & Hussain 1972).
Comparing this equation with Equation 3, the total Reynolds stress can be expressed as follows (Ge et al. 2008):
Ri j = −ρui u j = −ρ ũi ũ j − ρui u j ,
where ρ ũi ũ j is the contribution due to cycle-to-cycle variability and ρui u j is the contribution due to turbulence.
For more details, the reader is referred to Tiederman et al. (1988) and Ge et al. (2008).
EOA, the pressure drop p across the valve, and the maximum velocity Umax to estimate valve
performance (Peskin 1982, Yoganathan et al. 2004). In the past decade, however, a clear consensus
has emerged in the literature (Shadden et al. 2010) that using such parameters to characterize
heart valve hemodynamics is an overly simplified approach for flows dominated by rich coherent
structures and turbulence (Borazjani et al. 2008, Dasi et al. 2009, De Tullio et al. 2009). Thus, there
has been an increasing emphasis in the literature on high-fidelity FSI simulations (Sotiropoulos
et al. 2011, Votta et al. 2013), in vivo (Töger et al. 2012) and in vitro experiments (Miron et al.
2014), and coherent structure identification techniques (Shadden et al. 2010, Töger et al. 2012).
5. NATIVE VALVE HEMODYNAMICS

In pioneering computational work, McQueen & Peskin (2000) first attempted to quantify the
flow in a complete heart model by constructing an idealized FSI model of a generic heart with its
four valves using the classical diffused interface immersed boundary method (Peskin 1982) (see
Figure 2). In more recent years, our understanding of valvular hemodynamics at physiologic
conditions has been revolutionized by the rapid advent of noninvasive imaging modalities (Markl
et al. 2011, Carlsson et al. 2012, Sengupta et al. 2012), such as echocardiography, magnetic
resonance imaging, and computed tomography, and the integration of such modalities with
high-fidelity, patient-specific FSI numerical simulations (Le & Sotiropoulos 2013).
5.1. Mitral Valve

The complex anatomy, leaflet asymmetry, and dynamic deformation of the MV and its supporting
structures make the study of MV hemodynamics a rather challenging undertaking (McQueen
et al. 1982, Einstein et al. 2005, Lau et al. 2010, Sun et al. 2014). During the E-wave (see
Figure 1b), the blood flow velocity near the tips of the MV can reach as high as 0.6–1.2 m/s
(Yoganathan et al. 2004). Because the relative magnitude of the E- and A-wave peaks indicates
the ability of the LV to expand and the LA to contract, respectively, it has been postulated
that the E/A ratio is a good indicator of a subject’s heart-pumping ability and overall cardiac
health (Labovitz & Pearson 1987). Indeed, in healthy subjects, the E/A ratio is in the range
E/A ratio: ratio
between the peak 1–2 (Labovitz & Pearson 1987). Conversely, E/A ratios greater than 2 could indicate severe
measured velocity pathological conditions of the left heart (Labovitz & Pearson 1987).
magnitudes at the Early studies (Reul et al. 1981, McQueen et al. 1982, Garcia et al. 2000) showed that the opening
E-wave and A-wave, of the MV during the E-wave is associated with the formation of a vortex ring resulting from the
respectively
roll-up of the shear layer emanating from the leaflets of the MV (Shortland et al. 1996). In vitro
MVR: mitral vortex experiments further showed that the propagation of this mitral vortex ring (MVR) is much slower
ring
than the E-wave jet velocity (Pierrakos & Vlachos 2006). Because the formation of the MVR
Formation number, depends directly on the atrioventricular pressure gradient, several studies have related the MVR
L/D: the timescale of
propagation speed (v p ) to left heart dysfunction (Garcia et al. 2000; for more details, see the recent
vortex ring formation
in pulsatile flow in review in Bermejo et al. 2015). The MVR formation process has been confirmed in a number of
analogy to the recent computational studies (Baccani et al. 2003, Le & Sotiropoulos 2012, Chnafa et al. 2014)
piston/cylinder and in vivo experiments (Markl et al. 2011, Elbaz et al. 2014). Vortex ring formation phenomena
apparatus similar to those occurring during diastolic filling of the LV are ubiquitous in biological flows
Mitral eccentricity: (Dabiri & Gharib 2005), including other cardiovascular flows such as intracranial and abdominal
the lateral shift of the aneurysm hemodynamics (Salsac et al. 2006; Le et al. 2010, 2013b).
center of the effective
The fundamental vortex formation phenomena arising in the vicinity of the MV during the
mitral orifice from the
main left ventricular E-wave are similar to those occurring when a column of fluid is driven impulsively through an
base-apex axis orifice of diameter D by a cylindrical piston that moves for distance L before stopping (Gharib
et al. 1998). A striking finding in this regard is that cardiac health has also been associated with
optimal vortex ring formation (Gharib et al. 2006). However, the relationship between the vortex
formation number and LV pathologies is still a subject of debate (Stewart et al. 2012).
A distinct feature of LV flow (Le & Sotiropoulos 2012, Le et al. 2012, Fortini et al. 2013) is
that the MVR is a 3D and inclined vortex ring (Le et al. 2012). The MVR has been further shown
to interact with the LV wall (Le & Sotiropoulos 2012, Le et al. 2012, Fortini et al. 2013), giving
rise, at the end of diastole (Kilner et al. 2000), to a large-scale, asymmetric, clockwise rotating
vortex at the center of the LV. The sense of rotation of this vortex is thought to facilitate the
ejection of blood flow from the LV toward the aortic outflow track during systole (Pedrizzetti
& Domenichini 2005). The three-dimensionality and overall asymmetry of the MVR and the
subsequent formation of the large-scale LV vortex can be attributed to the 3D anatomy of the
MV and the confinement of the flow within a 3D and dynamically deforming LV domain. Most
computational (Baccani et al. 2003, Le & Sotiropoulos 2012, Chnafa et al. 2014) and in vitro
experimental (Fortini et al. 2013) studies to date have ignored the direct role of the anatomy
and dynamic deformation of the MV leaflets in MVR formation and LV flow phenomena. Such
studies have modeled the MV indirectly by prescribing a time-varying volume flow rate through
a fixed, circular mitral orifice. Idealized LV models have shown that the formation of the MVR
is highly sensitive to the location of the mitral annulus (Pedrizzetti & Domenichini 2005). Mitral
eccentricity has been shown to play a major role in regulating the overall structure and sense of
rotation of the LV flow (Pedrizzetti & Domenichini 2005, Pedrizzetti et al. 2010, Le 2011).
Recent computations in an anatomic and dynamically deforming LV with an indirect model
of the MV (Le et al. 2012, Chnafa et al. 2014) have been able to capture the inclined structure
of the MVR and further revealed complex secondary vortical structures broadly resembling, in
terms of complexity, those observed in impulsive vortex ring formation through inclined nozzles
(Le et al. 2011) (see Figure 3). That 3D vorticity dynamics broadly similar to those observed in
these computational studies have also begun to emerge in recent in vivo 4D-MRI studies (Elbaz
et al. 2014), as seen Figure 3b, suggests that the asymmetry and dynamic deformation of the
Le Gilmanov
a b
Helicity
16.0
9.6
3.2
–3.2
–9.6
–16.0
Figure 3
The formation of a mitral vortex ring in the left ventricle (LV) during diastole. (a) Numerical simulation of Le and colleagues (Le et al.
2012, Le & Sotiropoulos 2012). Shown is an isosurface of vorticity magnitude (|∇ × u|) colored with helicity (u · ∇ × u) contours. Here
u is the velocity vector. (Inset) The diastolic cycle marking the instance in time at which the vortex structure is shown (red dot). Panel a
adapted with permission from Le & Sotiropoulos (2012). Copyright 2012, AIP Publishing LLC. (b) Isosurface of λ2 ( Jeong & Hussain
1995) reconstruction of the mitral vortex ring at a similar instant in time as in panel a from in vivo 4D-MRI data (Elbaz et al. 2014).
The secondary vortex structures seen in the numerical simulation in panel a are also clearly visible in the in vivo data shown in panel b.
Panel b reproduced from Elbaz et al. (2014) with the permission of the Journal of Cardiovascular Magnetic Resonance.
LV and the precise location of the effective mitral orifice may indeed play a significant role in
determining the diastolic flow patterns in the LV. FSI simulations of the MV in idealized settings,
which take into account, to varying degrees of sophistication, the anatomy and deformation of
the valve leaflets, further show that the responses of the MV structures to blood flow are highly
asymmetrical (Einstein et al. 2005, Lau et al. 2010, Ma et al. 2013). In addition, the role of
chordae in regulating the dynamics of anterior and posterior leaflets is reported frequently in
computational works (Einstein et al. 2005, Lau et al. 2010, Ma et al. 2013). There is also evidence
that the dynamics of the mitral annulus and papillary muscles during LV relaxation can affect both
the kinematics of the MV leaflets and the chordae tendineae (Watton et al. 2008). In patients with
MV prostheses, clinical data further show that the sense of rotation of the LV flow may completely
reverse direction as compared to the native MV case (Faludi et al. 2010).
There is ample of evidence pointing to a relationship between LV pathology and intraven-
tricular flow patterns, notably the dynamics of the MVR (Hong et al. 2008, Carlhäll & Bolger
2010, Charonko et al. 2013, Mangual et al. 2013). The interaction of the MV leaflets and
supporting structures with the blood flow, however, is so complex (Charonko et al. 2013) that
a simple correlation among those factors is unlikely to exist (Stewart et al. 2012). Therefore,
improved understanding of MV hemodynamics is a critical prerequisite to bridge the gap between

theoretical models and clinical practice (Votta et al. 2013, Pedrizzetti & Domenichini 2014).
ASV: aortic sinus
vortex
5.2. Aortic Valve
Coronary ostia: inlet
area of the coronary As the AV opens during early systole, a shear layer develops that delineates the high-speed AV jet
arteries located in the from the slowly moving flow in the three sinuses (see Figure 1), causing entrainment of momentum
left and right coronary into the sinus and the formation of a large-scale vortex inside the sinus, the aortic sinus vortex
sinuses of Valsalva (ASV). Evidence of the existence of such a vortex, which was first sketched by Leonardo Da Vinci
(Gharib et al. 2002), has been reported in many in vitro (Peacock 1990, Querzoli et al. 2014)
and in vivo (Kilner et al. 1993, Bissell et al. 2014) studies. The curvature of the descending aorta
further increases the three-dimensionality of the flow and gives rise to a large-scale secondary
flow pattern in the thoracic aorta. In vivo data have indeed shown that in healthy subjects, the
so-emerging large-scale flow is a strong, right-handed, helical secondary flow in the descending
aorta (Kilner et al. 1993). Recent FSI computational evidence clarifying these processes in the
context of prosthetic trileaflet valves is presented in Section 6.2.
The physiologic significance of the ASV is not well understood and continues to be the subject
of debate in the literature (Kvitting et al. 2004, Markl et al. 2005, Bissell et al. 2014). Simplified
FSI models in straight aorta geometries suggest that the ASV could mediate WSS on the valve
leaflets and facilitate smooth closure of the AV (De Hart et al. 2003b). Although in vivo studies are
now providing data that can help clarify the formation mechanism and physiologic significance
of the ASV, subject-specific anatomic factors complicate the interpretation of such data (Kvitting
et al. 2004, Markl et al. 2005, Bissell et al. 2014). In addition, in vivo studies are limited by the
resolution of imaging modalities. For example, the resolution of present-day 4D-MRI techniques
is 2 mm in space and 20–40 ms in time (Sengupta et al. 2012). Such resolution is not sufficient
(Moore & Dasi 2014) to capture the dynamics of the ASV, which forms within 0.5–2.5 ms and
over spatial scales of the order of 50 μm.
Several authors have suggested that the sinus geometry plays an important role in regulating
the flow inside the aortic sinuses (sinus flow) (Saikrishnan et al. 2012, Yap et al. 2012). In vivo
data also demonstrate that sinus flow can be significantly altered when the natural geometry of the
aortic root is surgically modified (Kvitting et al. 2004, Markl et al. 2005). Furthermore, the ASV
has been shown to interact with the sinus walls, extracting vorticity of opposite sign and inducing a
secondary, counter-rotating vortex (annulus vortex ring) to form in the space between the annulus
and the ASV (Moore & Dasi 2014). The complex interaction between the ASV, annulus vortex ring,
and the valve leaflets could lead to high-frequency fluttering of the AV leaflets at frequencies greater
than 200 Hz at peak and late systole (Peacock 1990, Moore & Dasi 2014). Moreover, this complex
interaction may also cause the sinus flow to become turbulent, as evidenced by the results of in
vitro experiments revealing high turbulent kinetic energy within the ostia region (Peacock 1990).
Aortic sinus flow has a significant impact on the WSS dynamics on the leaflets of the AV (Yap
et al. 2012). Numerical simulations have shown that there is a sharp difference between the WSS
field on the ventricular versus the aortic side of the AV leaflets (Ge & Sotiropoulos 2010). On
the ventricular side, the WSS is generally high, and the limiting streamlines on the valve leaflets
are relatively unidirectional. On the aortic side of the leaflets, alternatively, the shear stress is
lower in magnitude and more dynamic, and the limiting streamlines exhibit complex topology
and singular points. These distinct differences in the shear stress patterns have been linked with
the propensity of the AV to develop calcification lesions on the aortic side of its leaflets (Ge &
Sotiropoulos 2010, Gould et al. 2013). Many pathological conditions [e.g., aortic root diseases
(Kvitting et al. 2004, Markl et al. 2005), aortic root replacement (Katayama et al. 2008), or BAV
Le Gilmanov
(Saikrishnan et al. 2012)] could lead to abnormal AV flow patterns (Barker et al. 2012). Extensive
studies in patients with a BAV, for example, suggest that its presence not only alters the sinus
flow (Saikrishnan et al. 2012), but also introduces nonphysiological flow patterns in the ascending
Aortic coarctation:
aorta (Hope et al. 2010), especially in conjunction with other pathological conditions such as aortic narrowing of the aorta,
coarctation (Keshavarz-Motamed et al. 2014). It has also been argued that in patients with BAV, typically acquired with
the WSS patterns on the aortic wall may be significantly different than those in healthy subjects other congenital heart
(Barker et al. 2010). Such differences have been linked to further clinical complications, such as diseases
aortic dilatation (den Reijer et al. 2010), calcific aortic stenosis (den Reijer et al. 2010), and aortic
aneurysms (Hope et al. 2007).
6. PROSTHETIC VALVE HEMODYNAMICS

PHVs are used to replace failed native valves. Present-day PHV designs can be classified in two
broad categories (see Figure 1d ): (a) rigid-leaflet or mechanical valves, which are made of synthetic
materials (metals, carbon) and can only be surgically implanted, and (b) valves with flexible leaflets
made either of synthetic materials (e.g., polymers) or biological tissue (bioprosthetic), which can
be implanted via conventional surgical procedures (surgical valves) or percutaneously via a catheter
(transcatheter valves) (Kheradvar et al. 2015).
Mechanical valve designs include a single pivoting disk, a caged spherical ball, and two flat
leaflets pivoting around their respective hinge mechanisms (Yoganathan et al. 2004). The latter
is referred to as a bileaflet mechanical heart valve (BMHV), and it is the most widely implanted
prosthesis today (Dasi et al. 2009). Flexible leaflet valve designs, alternatively, are inspired by the
bicuspid and tricuspid design of the native valves and can consist of either two or three flexible
leaflets. The leaflets are typically made from animal tissue (bioprosthetic valve) (Yoganathan
et al. 2004), polymers (polymeric valve) (Bezuidenhout et al. 2015), or tissue-engineered materials
(Ramaswamy et al. 2014, Kheradvar et al. 2015). In this review, we focus our discussion on the
hemodynamics of the BMHV and the flexible trileaflet prosthetic heart valve (TPHV) as these
are the two major valve prostheses today.
To date, all known heart valve prostheses have been linked to some kind of clinical compli-
cation resulting from the nonphysiologic flow patterns induced by their implantation (Dasi et al.
2009). BMHVs, for instance, are widely implanted because of their long-term durability, but the
nonphysiological hemodynamics they induce have been linked to several complications, such as
aortic stenosis, platelet activation, and blood clot formation (Yoganathan et al. 2005). Conse-
quently, patients with an implanted BMHV typically need to take anticoagulation medicines to
prevent such life-threatening clinical complications. On the contrary, TPHV designs maintain
the natural blood flow patterns but do not last as long as BMHVs (Dasi et al. 2009); consequently,
patients may need to receive another implant at some point in their lives. This reduced resilience
of TPHVs is the result of leaflet degeneration (e.g., calcification) or fatigue due to the mechanical
forces exerted on the flexible leaflets as they interact with the pulsatile blood flow (Yoganathan
et al. 2005).
Initially driven by the need for industrial standards and valve testing, experimental techniques
such as laser Doppler velocimetry and particle image velocimetry (PIV) have been extensively
employed to study PHV flows in vitro. Figure 4, for example, shows a snapshot of the flow field
generated by a TPHV implanted in a model LV system in the mitral position measured by PIV
(Kheradvar & Falahatpisheh 2012). In the past 10 years, computational fluid dynamics techniques
(De Tullio et al. 2009, Sotiropoulos & Borazjani 2009, Sotiropoulos et al. 2011, Votta et al.
2013, Sotiropoulos & Yang 2014) have advanced sufficiently to resolve important hemodynamic
features of PHV flows, including FSI phenomena, vortex formation and instability, and transition
Aortic Mitral
Figure 4
In vitro particle image velocimetry (PIV) measurements of vortex formation from a trileaflet prosthetic valve
placed in the mitral position inside a phantom model of the human left ventricle. Shown are 2D
instantaneous streamlines reconstructed from the PIV velocity fields. Figure reproduced from Kheradvar &
Falahatpisheh (2012) by permission from ICR Publishers Ltd, courtesy of Arash Kheradvar, University of
California, Irvine. For clarity some original labels were digitally replaced.
to turbulence (Borazjani et al. 2008, Le & Sotiropoulos 2013, De Tullio et al. 2009). The large-
scale flow structures induced by PHVs in the aortic position have also started to be observed in vivo
in recent MRI studies (von Knobelsdorff-Brenkenhoff et al. 2014), revealing distinct signatures
of the implanted valves on the flow patterns in the ascending aorta. For more details about the
linkages between PHV-induced flow patterns and clinical complications, the reader is referred to
Dasi et al. (2009).
6.1. Bileaflet Mechanical Heart Valves

The BMHV consists of two rigid leaflets, typically made of pyrolytic carbon, which can rotate
around their principal axes (Figure 1d ) with the rotational angle θ designed to vary between a
minimum (θ = θmin ) and a maximum (θmax ). The leaflets are rooted to the valve’s housing via
the hinge recess, which includes a 150-μm gap between the leaflet surface and the housing (the
b-datum gap) (see Figure 5a). These gaps, although necessary for the functioning of the valve,
are considered to be a weakness of the BMHV design as blood cells channeled through them
experience very high shear forces, increasing the risk for blood damage and blood clot formation
(Dasi et al. 2009). When implanted in the aortic position, the valve leaflets open swiftly, within
approximately 100 ms, at the start of systole and stay fully open for approximately 250 ms before
Le Gilmanov
a b
TSS 2D
max
(N/m2)
175
150
100
125
75
50
25
Figure 5
Flow dynamics past a bileaflet mechanical heart valve (BMHV). (a) Primary Reynolds shear stress in the wake of BMHV leaflets.
Panel a adapted from De Tullio et al. (2009), reproduced with permission from Cambridge University Press. (b) Coherent structures at
two instants near peak systole induced by a BMHV driven by a beating left ventricle (Le & Sotiropoulos 2013). The structures are
visualized by an isosurface of the Q-criterion (Hunt et al. 1988).
they start to close at the end of diastolic deceleration—the closing phase is typically completed
within approximately 100 ms.
Early studies of BMHV hemodynamics employed fixed-leaflet valve models (i.e., no FSI)
(Ge et al. 2003, 2005) and illustrated the triple-jet structure characterizing the flow in the wake
of the BMHV leaflets when the valve is fully open (Yoganathan et al. 2004). These jets form in
the space between the two leaflets (the b-datum jet) and in the space between each leaflet and the
aorta (the upper and lower leaflet jets).
Dasi et al. (2007) were the first to provide a comprehensive description of the underlying
phenomena with moving leaflets under physiologic pulsatile conditions using both numerical
simulations (Ge & Sotiropoulos 2007) and experimental measurements in a straight axisymmetric
aorta. Dasi et al.’s simulations, however, were carried out by prescribing the motion of the leaflets
from the laboratory experiments. Fully coupled FSI simulations were later reported both in a
straight aorta domain (Borazjani et al. 2008, De Tullio et al. 2009) (see Figure 5a) and in realistic
anatomic geometries (Borazjani et al. 2010, Le & Sotiropoulos 2013).
FSI simulations (Borazjani et al. 2008, De Tullio et al. 2009) and laboratory observations (Dasi
et al. 2007) have shown that as the leaflets reach the fully open position, they flutter slightly before
reaching equilibrium. The increase in the flow rate and the so-induced rapid change in leaflet
orientation lead to the formation of shear layers on both the upper and lower sides of each leaflet.
At the same time, the rapid opening of the two leaflets also forces the formation of a retrograde
jet toward the ventricular side (the b-datum opening jet) (Yun et al. 2014b). At the fully open
position, the shear layers shed from the leaflet tips roll up to create a start-up vortex ring in the
b-datum jet (Dasi et al. 2007, Ge & Sotiropoulos 2007, Borazjani et al. 2008, De Tullio et al.
2009, Le & Sotiropoulos 2013). This ring is rectangular in shape, stretched along the leaflet tips
toward the valve hinges. The short sides of this ring (near the hinges) travel faster than its long
sides, causing the ring to start folding about its minor axis (Dasi et al. 2007). Shear layers also
emanate from the junction of the valve housing and the sinuses and roll up into the sinus to form
a large-scale housing vortex ring, which begins to interact with the wall, extracting vorticity of
opposite sign (Dasi et al. 2007).
Vortex-vortex and vortex-wall interactions give rise to a very complex and highly 3D, albeit
still laminar, flow. As the peak flow is reached, the organized, large-scale coherent structures in the
wake of the leaflets undergo an explosive-like instability, breaking up into small-scale structures
(Dasi et al. 2007, De Tullio et al. 2009) and giving rise to pockets of high-turbulence stresses in the
wake of the leaflets (see Figure 5a). It is worth noting that phenomena such as the formation of the
central jet vortex ring, the roll-up of the flow and vortex formation in the sinuses, the emergence
of a Kármán-like street in the wake of the leaflets, and the explosive transition to turbulence near
peak systole occur both in straight and in anatomic aorta domains (Borazjani et al. 2008, 2010).
During the closing phase of the BMHV, the leaflets impact on the housing and have been shown
to exhibit a small rebound before reaching equilibrium at the fully closed position (Borazjani et al.
2008). Three leakage jets with retrograde flow are formed simultaneously: the b-datum and the
upper and lower leaflet closing jets. The upper and lower closing jets are formed from the sudden
reduction of the gap between the leaflet tip and housing (≈0.3 mm). The b-datum jet is created
as a result of the design of the two leaflets, which do not come in complete contact during closure
but rather leave a small gap of approximately 0.7 mm (Yun et al. 2014b). All three jets generate a
strong retrograde flow toward the LV side (extending up to approximately 2 aortic diameter), with
the strongest jet being the b-datum jet. In recent simulations that resolved the flow within these
leakage gaps during closing, Yun et al. (2014b) reported values for the instantaneous viscous shear
stresses as high as 300 dyn/cm2 during closing. These values are significantly higher than those
occurring in the wake of the leaflets, which do not exceed an instantaneous value of 150 dyn/cm2
(Ge et al. 2008). After the valve closes at the end of systole, viscous dissipation becomes dominant
inside the sinuses and the ascending aorta, causing the small-scale turbulence created in the wake
of the leaflets to decay slowly as systole comes to an end. On the contrary, the three leakage jets
continue to grow and penetrate deep into the ventricular side due to the retrograde flow during
diastole, and they could destabilize the flow in the LV outflow track (Le & Sotiropoulos 2013,
Yun et al. 2014b).
Given the clinical significance of the flow in the BMHV hinge recess, studies have aimed to
resolve the flow within these small gaps (Simon et al. 2010a,b; Yun et al. 2012). It is important to
note that, because of the size of these gaps (150 μm), the blood flow may no longer be considered
Newtonian, and its cellular nature needs to be taken into account. Simon et al. (2010a) proposed
a one-way coupled, multiscale strategy to resolve the hinge gaps without considering blood cells.
These simulations showed that the flow in the hinge recess is dominated by 3D separation, shear
layers, and strong leakage jets, and its details depend greatly on the geometrical design of the hinge
recess (Simon et al. 2010a). The calculated shear stresses reported for the St. Jude Medical BMHV,
for instance, reached values as high as approximately 2,000 dyn/cm2 during systole at the valve
upstream tip and 6,000 dyn/cm2 during diastole (Simon et al. 2010b). Yun et al. (2012) reported
a computational method for simulating the motion of platelets and quantifying the potential for
blood damage via fluid-structure interaction between blood elements and the flow within the
hinge recess of a BMHV.
Numerical simulations have also been carried out to investigate the performance of a BMHV
in a patient-specific left heart (Le & Sotiropoulos 2013) with the FSI between the flow and the
Le Gilmanov
valve leaflets driven by a deforming LV rather than a prescribed inflow waveform as in all previous
studies. This study showed that as the LV contracts during early systole, small-scale flow structures
created in the LV at the end of diastole are washed out toward the LV outflow tract and interact
TVR: tip vortex ring
with the valve leaflets. Although the main features of the resulting BMHV flow are similar to those
of in vitro experiments and numerical simulations in straight aorta domains, the interactions of
the complex flow from the LV with the valve leaflets, the sinuses, and the ascending aorta give rise
to significant differences, as discussed in detail in Le & Sotiropoulos (2013) (see also Figure 5b).
The most striking differences include the asymmetric kinematics of the two leaflets and the strong
leakage jets that form between the closing leaflets and also the hinge regions at the end of systole
(Borazjani & Sotiropoulos 2010, Borazjani et al. 2010). These leakage jets penetrate deep into the
LV domain, revealing a strong coupling between the BMHV flow and ventricular hemodynamics
(Le & Sotiropoulos 2013; Yun et al. 2014a,b).
6.2. Trileaflet Flexible Valves

A TPHV consists of two main components: (a) three (nonfiber or fiber-reinforced) flexible leaflets
and (b) a rigid supporting structure (housing/stent) (see Figure 1e). A transcatheter TPHV also
includes an expandable stent that helps keep the valve in place on the aorta wall (Kheradvar et al.
2015). The leaflets are thin, with typical thickness in the range of few hundred micrometers, are
attached to the supporting structures, and meet together at the valve commissures. Depending on
the design, the leaflets can coapt at different levels, as well as allow leakage flows at the commissures
during diastole.
TPHVs are typically implanted in the aortic position in which, because of their geometric
similarity to the native AV, they largely preserve the physiologic flow patterns and thus help
enhance the functionality of the aortic root and coronary flows (Mannacio et al. 2012). Therefore,
the flow patterns generated by a TPHV are broadly similar to those discussed above for the
AV.
As the TPHV opens, the shear layer emanating from the valve leaflets rolls up to form a three-
lobbed vortex ring, termed a tip vortex ring (TVR). The TVR has been documented in high-
resolution in vitro experiments (Saikrishnan et al. 2012, Moore & Dasi 2014) and FSI simulations
of AVs in simplified, straight aorta domains (Borazjani 2013, Le et al. 2013a). This ring, however,
has yet to be documented in vivo for either an AV or an implanted TPHV because of the previously
discussed resolution requirements of present-day imaging modalities (Moore & Dasi 2014). Recent
simulations from our group (Figure 6) illustrate for the first time the underlying phenomena
during early systole for a polymeric valve in an anatomic curved aorta. As seen in Figure 6a, the
three-lobed TVR becomes highly distorted, as each lobe bends forward, propagating faster than
the rest of the ring. The ensuing vortex-vortex and vortex-wall interactions cause the TVR to
grow into a topologically complex, 3D structure (see Figure 6b), ultimately breaking up into a
dynamically rich, disorganized state dominated by small-scale vortical structures. The formation
and breakup of the TVR into small-scale turbulence take place approximately within 100 ms
from the valve’s initial opening. Figure 6c also illustrates the large-scale flow patterns in the
ascending aorta near peak systole. Instantaneous streamlines colored with the velocity magnitude
are used in this figure to enable direct qualitative comparisons with in vivo 4D-MRI data that
are now producing similar visualizations of the flow (Bissell et al. 2014). Figure 6c underscores
the aforementioned similarity between the AV and TPHV large-scale flow patterns (Bissell et al.
2014, von Knobelsdorff-Brenkenhoff et al. 2014). In agreement with in vivo 4D-MRI data (Bissell
et al. 2014), it clearly illustrates the formation of the previously discussed ASV and the onset of a
counterclockwise helical flow in the ascending aorta.
a c
V (m/s)
2.1
1.8
1.5
1.2
0.9
0.6
0.3
0
Figure 6
Flow-structure interaction (FSI) simulation of a trileaflet prosthetic heart valve in an anatomic aorta. The aorta is rigid, and the flexible
valve leaflets are simulated using a homogeneous thin shell with thickness h = 6 × 10−4 m, Young modulus E = 1 MPa, and Poisson
ratio of 0.35. The results have been obtained using the FSI curvilinear immersed boundary method with the thin-shell, rotation-free
finite element model for the valve leaflets (Stolarski et al. 2013). (a,b) An isosurface of the Q-criterion (Hunt et al. 1988) at two instants
in the cardiac cycle, visualizing (a) the formation of the tip vortex ring from the valve leaflets (bottom) and (b) the subsequent rapid
growth in the topological complexity of this structure (top) during early systole. (c) Instantaneous streamlines colored with velocity
magnitude contours at peak systole, illustrating the formation of the aortic sinus vortex and the onset of counterclockwise spiral
secondary motion in the ascending aorta. The red dot in each inset marks the instant in time during systole when the flow is visualized.
The large-scale structure of TPHV flow in the ascending aorta is divided into two areas: the cen-
tral jet and the reversed flow regions. These regions have been observed in both experiments (Leo
et al. 2005, Querzoli et al. 2014) and numerical simulations (Griffith 2012). The central jet spreads
radially from the valve’s tip and creates pockets of Reynolds stresses as high as 4,500 dyn/cm2
in the commissural region during systole and diastole. This flow feature suggests that hemolysis,
Le Gilmanov
blood damage, and thrombi formation could occur (Leo et al. 2006) in the vicinity of the valve and
the supporting stents. Depending on the valve design, leakage jets may also occur during diastole
through the commissure gaps, with velocities as high as 2 m/s (Leo et al. 2005). These leakage
Thrombogenicity:
flows can cause significant differences between the WSS fields on the aortic side. On the ventricu- tendency of tissues in
lar side, the WSS can reach up to 80 dyn/cm2 during systole, whereas on the aortic side the WSS contact with blood to
is lower and does not exceed 20 dyn/cm2 during systole (Yap et al. 2012). These differences are develop thrombi or
attributed to the differences discussed above in the hemodynamics in the ventricular and aortic clots; the detachment
of clots into the blood
sides of the valve.
flow can increase
In vivo studies have revealed marked differences in the ascending aorta hemodynamics between stroke risk
a BMHV and a TPHV when implanted in the aortic position (von Knobelsdorff-Brenkenhoff
et al. 2014). These results are consistent with computational findings, which have shown distinctly
different vorticity dynamics in the ascending aorta between TPHV and BMHV implants (Borazjani
2013). Such differences, which are naturally to be expected because of the major differences in
the designs of the two valves, clearly underscore the aforementioned nonphysiologic flow patterns
induced by a BMHV.
Two important factors determine the dynamics of the FSI between blood flow and valve leaflets
and govern the structural performance of a TPHV, namely the leaflet geometry and the leaflet
material properties. Although material properties are not a focus of this review (see Sacks et al.
2009a for a detailed discussion of such issues), we note that for homogeneous material (i.e., without
fibers), it has been shown that the leaflet thickness plays a dominant role in determining the overall
hemodynamic performance (Bernacca et al. 2002). When the leaflets are fiber reinforced (e.g.,
porcine tissues) (Driessen et al. 2005), the distribution of the collagen fiber direction plays an
important role in regulating the leaflet kinematics (De Hart et al. 2003a), as well as the shear stress
distribution and the opening area (Marom et al. 2013). Commissure design is also an important
feature as it affects the diastolic leakage velocity and the resulting shear stress field on the ventricular
side of the valve (Leo et al. 2006).
6.3. Implantation
The successful implantation of a PHV depends greatly on the skill and experience of the surgeon
who performs the procedure (van’t Veer et al. 2007). Choosing an optimal PHV design is a
difficult decision given that the surgeon must balance the potential benefits of the replacement
against the risks arising from possible clinical complications (Pibarot & Dumesnil 2009). Such a
decision also needs to be personalized because the surgeon needs to consider the specific anatomic
factors of the patient, which will determine the valve size and the exact location and orientation
of the implant (Rahimtoola 2003). Selecting a specific valve type (e.g., a BMHV versus TPHV)
depends on several parameters, including age, cardiovascular diseases, and the likelihood of the
occurrence of thrombogenicity and hemolysis (Rahimtoola 2003). Surgeons have long realized that
the exact orientation of the PHV implant is especially important (if not crucial) for successful long-
term management of the disease (Mächler et al. 2004). The risks of thrombosis and regurgitant
flow have been linked to the way the valve is placed (Pibarot & Dumesnil 2009). Furthermore,
postoperative hemodynamic evaluation of PHVs (Zoghbi et al. 2009) can now be done routinely
in clinical practice, and such evaluations provide significant new insights into the effect of PHV
implants on intraventricular flow (von Knobelsdorff-Brenkenhoff et al. 2014).
At the aortic position, clinical studies (Rajappan et al. 2003) have reported that the physiologic
flow pattern is highly altered after valve replacement (Laas et al. 1999). An important factor is the
microcirculation in the coronary arteries, which can be significantly modified (Sabbah & Stein
1982), especially in patients with aortic stenosis (Mannacio et al. 2012). Comparisons of BMHVs
implanted in straight and anatomic aortas (Borazjani et al. 2010) showed that the formation of
the vortex ring associated with the b-datum jet and the housing jet are much delayed in the
anatomic case. This phenomenon was shown to delay the explosive transition to turbulence, as
well as give rise to distinct differences in the shear stress dynamics along the ascending aorta
wall for the anatomic case (Borazjani et al. 2010). Another important finding from this study is
the asymmetrical response of the valve leaflet kinematics during early systole. The most striking
difference, however, occurs in the closing phase of the valve when only one of the two leaflets
exhibits a large rebound after the full valve closure. It was further shown that the asymmetry
of leaflet kinematics (i.e., the lazy leaflet effect) is dependent on the valve orientation (anatomic
versus anti-anatomic orientation) (Borazjani & Sotiropoulos 2010). These results are supported
by experimental data (Yagi et al. 2011) showing that the orientation of the implanted BMHV
regulates the dynamics of the sinus vortex at the end of systole (De Tullio et al. 2011).
At the mitral position, computational (Choi et al. 2014) and experimental (Pierrakos & Vlachos
2006, Querzoli et al. 2010) studies reported that the implanted BMHV can profoundly alter the
LV flow (Van Rijk-Zwikker et al. 1996, Mächler et al. 2004). The interaction between the housing
vortex and TVRs induces pockets of turbulence stresses as high as 2,000 dyn/cm2 (Querzoli et al.
2010). Furthermore, the orientation of the BMHV was also shown to be important (Pierrakos &
Vlachos 2006, Choi et al. 2014) as it determines to a large extent the asymmetrical response of
the leaflets, as well as the interaction between the b-datum jet and the ventricular wall.
7. FUTURE CHALLENGES
From a computational standpoint, the future frontier for fluid mechanics of heart valves is the abil-
ity to carry out accurate FSI simulations in patient-specific anatomies and across different scales.
Computational methods must integrate the continuum approximation of blood flow to simulate
large-scale hemodynamics, with multiscale models to account for mechanical stimuli at the level
of blood elements and endothelial cells on the valve leaflets and surrounding vessels (Weinberg
et al. 2010). Major future challenges arise from the need to (a) develop accurate structural models
accounting for the flexibility of valvular leaflets (Sacks et al. 2009b) and their composite structures
(Sacks et al. 2009a, Calleja et al. 2013), a challenge that is even more daunting for the native
MV; (b) take into account the complex cardiac anatomy, the dynamic deformation of the ventri-
cles, and the compliance of the arterial walls (Sacks & Sun 2003, Taylor & Figueroa 2009); and
(c) develop multiscale prediction models for tissue growth and degeneration (Taylor & Figueroa
2009). Innovative experimental approaches are also needed to validate computational models in
vivo. From the experimental perspective, the linkages between valve hemodynamics and disease
pathways as well as clinical complications require the use of integrated multimodality approaches
that incorporate information across a range of scales and bridge the gap between mechanics and
biology (Hinton & Yutzey 2011).
8. CONCLUSIONS
It is now well recognized that the fluid mechanics of heart valves involve a broad range of complex
multiscale mechanobiological phenomena. Therefore, the study of heart valve hemodynamics ne-
cessitates the integration of different modalities (in vivo, in vitro, and in silico) across a range of
scales. The richness of vortical structures arising in heart valve flows and the clearly documented
transition to turbulence necessitate the use of high-resolution, multiscale computational, and in
vivo and in vitro experimental techniques in a complementary approach. In such a way, the fluid
mechanic characteristics can be interpreted and understood from the organ to cellular scales in a
Le Gilmanov
systematic way. This knowledge will help establish links between hemodynamics and valvular dis-
ease pathways and help develop effective therapies, and it will also provide the basis for optimizing
the design of heart valve replacements in a patient-specific basis.
SUMMARY POINTS
1. The interaction between blood flow and heart valves is complicated by the anatomic
geometry and large deformation of arterial wall and valve tissues.
2. Vortex formation, instability, and transition to turbulence characterize valvular flows and
influence the WSS fields on the valve leaflets.
3. The geometry and material properties of heart valves can have a profound impact on
valvular hemodynamics.
4. The location and orientation of prosthetic valve implantation play an important role in
the resulting hemodynamics and can affect the long-term success of valve replacement.
FUTURE ISSUES
1. Improved experimental techniques and imaging modalities should be developed to cap-
ture the kinematics of the valve leaflets and associated flow patterns in vivo and in vitro.
2. Better structural models are needed for biological tissues.
3. New computational techniques are required that are capable of multiscale simulations
from organ to cellular scales with diseases.
4. New fluid mechanics measures need to be developed to characterize vortex dynamics in
the heart and quantify linkages with pathological conditions.
DISCLOSURE STATEMENT
The authors are not aware of any biases that might be perceived as affecting the objectivity of this
review.
ACKNOWLEDGMENTS
We acknowledge the support of NIH grant RO1-HL70262-08 that provided financial support for
our early works and a grant from the University of Minnesota Lillehei Heart Institute. We also
greatly appreciate the support of Minnesota Supercomputing for the computational time in our
works. Trung Bao Le was partially supported by a predoctoral fellowship from Vietnam Education
Foundation and United States National Academies. The lead author (Fotis Sotiropoulos) is also
grateful to Ajit Yoganathan for pointing him to the study of heart valve fluid mechanics early on
during his career.
LITERATURE CITED
Askov JB, Honge JL, Jensen MO, Nygaard H, Hasenkam JM, Nielsen SL. 2013. Significance of force transfer
in mitral valve–left ventricular interaction: in vivo assessment. J. Thorac. Cardiovasc. Surg. 145:1635–41
Baccani B, Domenichini F, Pedrizzetti G. 2003. Model and influence of mitral valve opening during the left
ventricular filling. J. Biomech. 36:355–61
Barker AJ, Lanning C, Shandas R. 2010. Quantification of hemodynamic wall shear stress in patients with
bicuspid aortic valve using phase-contrast MRI. Ann. Biomed. Eng. 38:788–800
Barker AJ, Markl M. 2011. The role of hemodynamics in bicuspid aortic valve disease. Eur. J. Cardio-Thorac.
Surg. 39:805–6
Barker AJ, Markl M, Bürk J, Lorenz R, Bock J, et al. 2012. Bicuspid aortic valve is associated with altered wall
shear stress in the ascending aorta. Circ. Cardiovasc. Imaging 5:457–66
Bermejo J, Martı́nez-Legazpi P, del Álamo JC. 2015. The clinical assessment of intraventricular flows. Annu.
Rev. Fluid Mech. 47:315–42
Bernacca GM, O’Connor B, Williams DF, Wheatley DJ. 2002. Hydrodynamic function of polyurethane
prosthetic heart valves: influences of Young’s modulus and leaflet thickness. Biomaterials 23:45–50
Bezuidenhout D, Williams DF, Zilla P. 2015. Polymeric heart valves for surgical implantation, catheter-based
technologies and heart assist devices. Biomaterials 36:6–25
Bissell MM, Dall’Armellina E, Choudhury RP. 2014. Flow vortices in the aortic root: In vivo 4D-MRI confirms
predictions of Leonardo da Vinci. Eur. Heart J. 35:1344

Borazjani I. 2013. Fluid–structure interaction, immersed boundary-finite element method simulations of bio-
prosthetic heart valves. Comput. Methods Appl. Mech. Eng. 257:103–16
Borazjani I, Ge L, Sotiropoulos F. 2008. Curvilinear immersed boundary method for simulating fluid structure
interaction with complex 3D rigid bodies. J. Comput. Phys. 227:7587–620
Borazjani I, Ge L, Sotiropoulos F. 2010. High-resolution fluid–structure interaction simulations of flow
through a bi-leaflet mechanical heart valve in an anatomic aorta. Ann. Biomed. Eng. 38:326–44
Borazjani I, Sotiropoulos F. 2010. The effect of implantation orientation of a bileaflet mechanical heart valve
on kinematics and hemodynamics in an anatomic aorta. J. Biomech. Eng. 132:111005
Braverman AC, Güven H, Beardslee MA, Makan M, Kates AM, Moon MR. 2005. The bicuspid aortic valve.
Curr. Probl. Cardiol. 30:470–522
Calleja A, Thavendiranathan P, Ionasec RI, Houle H, Liu S, et al. 2013. Automated quantitative 3-dimensional
modeling of the aortic valve and root by 3-dimensional transesophageal echocardiography in normals,
aortic regurgitation, and aortic stenosis comparison to computed tomography in normals and clinical
implications. Circ. Cardiovasc. Imaging 6:99–108
Carlhäll CJ, Bolger A. 2010. Passing strange flow in the failing ventricle. Circ. Heart Fail. 3:326–31
Carlsson M, Heiberg E, Toger J, Arheden H. 2012. Quantification of left and right ventricular kinetic energy
using four-dimensional intracardiac magnetic resonance imaging flow measurements. Am. J. Physiol.
Heart Circ. Physiol. 302:H893–900
Chaput M, Handschumacher MD, Tournoux F, Hua L, Guerrero JL, et al. 2008. Mitral leaflet adaptation
to ventricular remodeling occurrence and adequacy in patients with functional mitral regurgitation.
Circulation 118:845–52
Charonko JJ, Kumar R, Stewart K, Little WC, Vlachos PP. 2013. Vortices formed on the mitral valve tips aid
normal left ventricular filling. Ann. Biomed. Eng. 41:1049–61
Chester AH, El-Hamamsy I, Butcher JT, Latif N, Bertazzo S, Yacoub MH. 2014. The living aortic valve:
from molecules to function. Glob. Cardiol. Sci. Pract. 2014:52–77
Chnafa C, Mendez S, Nicoud F. 2014. Image-based large-eddy simulation in a realistic left heart. Comput.
Fluids 94:173–87
Choi YJ, Vedula V, Mittal R. 2014. Computational study of the dynamics of a bileaflet mechanical heart valve
in the mitral position. Ann. Biomed. Eng. 42:1668–80
Dabiri JO, Gharib M. 2005. The role of optimal vortex formation in biological fluid transport. Proc. R. Soc. B
272:1557–60
Dasi LP, Ge L, Simon H, Sotiropoulos F, Yoganathan A. 2007. Vorticity dynamics of a bileaflet mechanical
heart valve in an axisymmetric aorta. Phys. Fluids 19:067105
Dasi LP, Simon HA, Sucosky P, Yoganathan AP. 2009. Fluid mechanics of artificial heart valves. Clin. Exp.
Pharmacol. Physiol. 36:225–37
De Hart J, Baaijens F, Peters G, Schreurs P. 2003a. A computational fluid-structure interaction analysis of a
fiber-reinforced stentless aortic valve. J. Biomech. 36:699–712
Le Gilmanov
De Hart J, Peters G, Schreurs P, Baaijens F. 2003b. A three-dimensional computational analysis of fluid–

structure interaction in the aortic valve. J. Biomech. 36:103–12
De Tullio M, Cristallo A, Balaras E, Verzicco R. 2009. Direct numerical simulation of the pulsatile flow
through an aortic bileaflet mechanical heart valve. J. Fluid Mech. 622:259–90
De Tullio M, Pedrizzetti G, Verzicco R. 2011. On the effect of aortic root geometry on the coronary entry-flow
after a bileaflet mechanical heart valve implant: a numerical study. Acta Mech. 216:147–63
den Reijer PM, Sallee D III, van der Velden P, Zaaijer ER, Parks WJ, et al. 2010. Hemodynamic predic-
tors of aortic dilatation in bicuspid aortic valve by velocity-encoded cardiovascular magnetic resonance.
J. Cardiovasc. Magn. Reson. 12:4
Driessen NJ, Bouten CV, Baaijens FP. 2005. Improved prediction of the collagen fiber architecture in the
aortic heart valve. J. Biomech. Eng. 127:329–36
Einstein DR, Kunzelman KS, Reinhall PG, Nicosia M, Cochran R. 2005. Non-linear fluid-coupled compu-
tational model of the mitral valve. J. Heart Valve Dis. 14:376–85
Elbaz MS, Calkoen EE, Westenberg JJ, Lelieveldt BP, Roest AA, van der Geest RJ. 2014. Vortex flow during
early and late left ventricular filling in normal subjects: quantitative characterization using retrospectively-
gated 4D flow cardiovascular magnetic resonance and three-dimensional vortex core analysis. J. Cardio-
vasc. Magn. Reson. 16:78

Faludi R, Szulik M, D’hooge J, Herijgers P, Rademakers F, et al. 2010. Left ventricular flow patterns in healthy
subjects and patients with prosthetic mitral valves: an in vivo study using echocardiographic particle image
velocimetry. J. Thorac. Cardiovasc. Surg. 139:1501–10
Forouhar AS, Liebling M, Hickerson A, Nasiraei-Moghaddam A, Tsai HJ, et al. 2006. The embryonic verte-
brate heart tube is a dynamic suction pump. Science 312:751–53
Fortini S, Querzoli G, Espa S, Cenedese A. 2013. Three-dimensional structure of the flow inside the left
ventricle of the human heart. Exp. Fluids 54:1609
Freund JB. 2014. Numerical simulation of flowing blood cells. Annu. Rev. Fluid Mech. 46:67–95
Garcia MJ, Smedira NG, Greenberg NL, Main M, Firstenberg MS, et al. 2000. Color M-mode Doppler
flow propagation velocity is a preload insensitive index of left ventricular relaxation: animal and human
validation. J. Am. Coll. Cardiol. 35:201–8
Ge L, Dasi LP, Sotiropoulos F, Yoganathan AP. 2008. Characterization of hemodynamic forces induced by
mechanical heart valves: Reynolds versus viscous stresses. Ann. Biomed. Eng. 36:276–97
Ge L, Jones SC, Sotiropoulos F, Healy TM, Yoganathan AP. 2003. Numerical simulation of flow in mechanical
heart valves: grid resolution and the assumption of flow symmetry. J. Biomech. Eng. 125:709–18
Ge L, Leo HL, Sotiropoulos F, Yoganathan AP. 2005. Flow in a mechanical bileaflet heart valve at laminar
and near-peak systole flow rates: CFD simulations and experiments. J. Biomech. Eng. 127:782–97
Ge L, Sotiropoulos F. 2007. A numerical method for solving the 3D unsteady incompressible Navier–Stokes
equations in curvilinear domains with complex immersed boundaries. J. Comput. Phys. 225:1782–809
Ge L, Sotiropoulos F. 2010. Direction and magnitude of blood flow shear stresses on the leaflets of aortic
valves: Is there a link with valve calcification? J. Biomech. Eng. 132:014505
Gharib M, Kremers D, Koochesfahani M, Kemp M. 2002. Leonardo’s vision of flow visualization. Exp. Fluids
33:219–23
Gharib M, Rambod E, Kheradvar A, Sahn DJ, Dabiri JO. 2006. Optimal vortex formation as an index of
cardiac health. PNAS 103:6305–8
Gharib M, Rambod E, Shariff K. 1998. A universal time scale for vortex ring formation. J. Fluid Mech.
360:121–40
Gould ST, Srigunapalan S, Simmons CA, Anseth KS. 2013. Hemodynamic and cellular response feedback in
calcific aortic valve disease. Circ. Res. 113:186–97
Grande-Allen KJ, Barber JE, Klatka KM, Houghtaling PL, Vesely I, et al. 2005. Mitral valve stiffening in
end-stage heart failure: evidence of an organic contribution to functional mitral regurgitation. J. Thorac.
Cardiovasc. Surg. 130:783–90
Griffith BE. 2012. Immersed boundary model of aortic heart valve dynamics with physiological driving and
loading conditions. Int. J. Numer. Methods Biomed. Eng. 28:317–45
Hinton RB, Yutzey KE. 2011. Heart valve structure and function in development and disease. Annu. Rev.
Physiol. 73:29–46
Hong GR, Pedrizzetti G, Tonti G, Li P, Wei Z, et al. 2008. Characterization and quantification of vortex
flow in the human left ventricle by contrast echocardiography using vector particle image velocimetry.
JACC Cardiovasc. Imaging 1:705–17
Hope MD, Hope TA, Meadows AK, Ordovas KG, Urbania TH, et al. 2010. Bicuspid aortic valve: four-
dimensional MR evaluation of ascending aortic systolic flow patterns. Radiology 255:53–61
Hope TA, Markl M, Wigström L, Alley MT, Miller DC, Herfkens RJ. 2007. Comparison of flow patterns in
ascending aortic aneurysms and volunteers using four-dimensional magnetic resonance velocity mapping.
J. Magn. Reson. Imaging 26:1471–79
Hunt JC, Wray A, Moin P. 1988. Eddies, streams, and convergence zones in turbulent flows. In Studying
Turbulence Using Numerical Simulation Databases, 2: Proc. 1998 Summer Prog., pp. 193–208. Stanford, CA:
Cent. Turbul. Res.
Hwang N, Hussain A, Hui P, Stripling T, Wieting D. 1977. Turbulent flow through a natural human mitral
valve. J. Biomech. 10:59–67
Jeong J, Hussain F. 1995. On the identification of a vortex. J. Fluid Mech. 285:69–94
Katayama S, Umetani N, Sugiura S, Hisada T. 2008. The sinus of Valsalva relieves abnormal stress on aortic
valve leaflets by facilitating smooth closure. J. Thorac. Cardiovasc. Surg. 136:1528–35

Keshavarz-Motamed Z, Garcia J, Gaillard E, Maftoon N, Di Labbio G, et al. 2014. Effect of coarctation of
the aorta and bicuspid aortic valve on flow dynamics and turbulence in the aorta using particle image
velocimetry. Exp. Fluids 55:1696
Kheradvar A, Falahatpisheh A. 2012. The effects of dynamic saddle annulus and leaflet length on transmitral
flow pattern and leaflet stress of a bileaflet bioprosthetic mitral valve. J. Heart Valve Dis. 21:225–33
Kheradvar A, Groves EM, Dasi LP, Alavi SH, Tranquillo R, et al. 2015. Emerging trends in heart valve
engineering: Part I. Solutions for future. Ann. Biomed. Eng. 43:833–43
Kilner PJ, Yang GZ, Mohiaddin RH, Firmin DN, Longmore DB. 1993. Helical and retrograde secondary flow
patterns in the aortic arch studied by three-directional magnetic resonance velocity mapping. Circulation
88:2235–47
Kilner PJ, Yang GZ, Wilkes AJ, Mohiaddin RH, Firmin DN, Yacoub MH. 2000. Asymmetric redirection of
flow through the heart. Nature 404:759–61
Ku DN. 1997. Blood flow in arteries. Annu. Rev. Fluid Mech. 29:399–434
Kvitting JPE, Ebbers T, Wigström L, Engvall J, Olin CL, Bolger AF. 2004. Flow patterns in the aortic root
and the aorta studied with time-resolved, 3-dimensional, phase-contrast magnetic resonance imaging:
implications for aortic valve–sparing surgery. J. Thorac. Cardiovasc. Surg. 127:1602–7
Laas J, Kleine P, Hasenkam MJ, Nygaard H. 1999. Orientation of tilting disc and bileaflet aortic valve
substitutes for optimal hemodynamics. Ann. Thorac. Surg. 68:1096–99
Labovitz AJ, Pearson AC. 1987. Evaluation of left ventricular diastolic function: clinical relevance and recent
Doppler echocardiographic insights. Am. Heart J. 114:836–51
Lau K, Diaz V, Scambler P, Burriesci G. 2010. Mitral valve dynamics in structural and fluid–structure inter-
action models. Med. Eng. Phys. 32:1057–64
Le TB. 2011. A computational framework for simulating cardiovascular flows in patient-specific anatomies. PhD
Thesis, Univ. Minnesota, Minneapolis
Le TB, Borazjani I, Kang S, Sotiropoulos F. 2011. On the structure of vortex rings from inclined nozzles.
J. Fluid Mech. 686:451–83
Le TB, Borazjani I, Sotiropoulos F. 2010. Pulsatile flow effects on the hemodynamics of intracranial aneurysms.
J. Biomech. Eng. 132:111009
Le TB, Gilmanov A, Sotiropoulos F. 2013a. High resolution simulation of tri-leaflet aortic heart valve in an
idealized aorta. J. Med. Devices 7:030930
Le TB, Sotiropoulos F. 2012. On the three-dimensional vortical structure of early diastolic flow in a patient-
specific left ventricle. Eur. J. Mech. B Fluids 35:20–24
Le TB, Sotiropoulos F. 2013. Fluid–structure interaction of an aortic heart valve prosthesis driven by an
animated anatomic left ventricle. J. Comput. Phys. 244:41–62
Le TB, Sotiropoulos F, Coffey D, Keefe D. 2012. Vortex formation and instability in the left ventricle. Phys.
Fluids 24:091110
Le Gilmanov
Le TB, Troolin DR, Amatya D, Longmire EK, Sotiropoulos F. 2013b. Vortex phenomena in sidewall aneurysm
hemodynamics: experiment and numerical simulation. Ann. Biomed. Eng. 41:2157–70
Leo HL, Dasi LP, Carberry J, Simon HA, Yoganathan AP. 2006. Fluid dynamic assessment of three polymeric
heart valves using particle image velocimetry. Ann. Biomed. Eng. 34:936–52
Leo HL, Simon H, Carberry J, Lee SC, Yoganathan AP. 2005. A comparison of flow field structures of two
tri-leaflet polymeric heart valves. Ann. Biomed. Eng. 33:429–43
Ma X, Gao H, Griffith BE, Berry C, Luo X. 2013. Image-based fluid–structure interaction model of the human
mitral valve. Comput. Fluids 71:417–25
Mächler H, Perthel M, Reiter G, Reiter U, Zink M, et al. 2004. Influence of bi-leaflet prosthetic mitral valve
orientation on left ventricular flow and experimental in vivo magnetic resonance imaging study. Eur. J.
Cardio-Thorac. Surg. 26:747–53
Mangual JO, Kraigher-Krainer E, De Luca A, Toncelli L, Shah A, et al. 2013. Comparative numerical study
on left ventricular fluid dynamics after dilated cardiomyopathy. J. Biomech. 46:1611–17
Mannacio V, Di Tommaso L, De Amicis V, Stassano P, Vosa C. 2012. Coronary perfusion: impact of flow
dynamics and geometric design of 2 different aortic prostheses of similar size. J. Thorac. Cardiovasc. Surg.
143:1030–35
Markl M, Draney MT, Miller DC, Levin JM, Williamson EE, et al. 2005. Time-resolved three-dimensional
magnetic resonance velocity mapping of aortic flow in healthy volunteers and patients after valve-sparing
aortic root replacement. J. Thorac. Cardiovasc. Surg. 130:456–63
Markl M, Kilner PJ, Ebbers T. 2011. Comprehensive 4D velocity mapping of the heart and great vessels by
cardiovascular magnetic resonance. J. Cardiovasc. Magn. Reson. 13:7
Marom G, Peleg M, Halevi R, Rosenfeld M, Raanani E, et al. 2013. Fluid-structure interaction model of
aortic valve with porcine-specific collagen fiber alignment in the cusps. J. Biomech. Eng. 135:101001
McQueen DM, Peskin CS. 2000. A three-dimensional computer model of the human heart for studying
cardiac fluid dynamics. ACM Siggraph Comput. Graph. 34:56–60
McQueen DM, Peskin CS, Yellin EL. 1982. Fluid dynamics of the mitral valve: physiological aspects of a
mathematical model. Am. J. Physiol. 242:1095–110
Miron P, Vétel J, Garon A. 2014. On the use of the finite-time Lyapunov exponent to reveal complex flow
physics in the wake of a mechanical valve. Exp. Fluids 55:1814
Moore B, Dasi LP. 2014. Spatiotemporal complexity of the aortic sinus vortex. Exp. Fluids 55:1770
Peacock JA. 1990. An in vitro study of the onset of turbulence in the sinus of Valsalva. Circ. Res. 67:448–60
Pedrizzetti G, Domenichini F. 2005. Nature optimizes the swirling flow in the human left ventricle. Phys. Rev.
Lett. 95:108101
Pedrizzetti G, Domenichini F. 2014. Left ventricular fluid mechanics: the long way from theoretical models
to clinical applications. Ann. Biomed. Eng. 43:26–40
Pedrizzetti G, Domenichini F, Tonti G. 2010. On the left ventricular vortex reversal after mitral valve re-
placement. Ann. Biomed. Eng. 38:769–73
Peskin CS. 1982. The fluid dynamics of heart valves: experimental, theoretical, and computational methods.
Annu. Rev. Fluid Mech. 14:235–59
Pibarot P, Dumesnil JG. 2009. Prosthetic heart valves selection of the optimal prosthesis and long-term
management. Circulation 119:1034–48
Pierrakos O, Vlachos PP. 2006. The effect of vortex formation on left ventricular filling and mitral valve
efficiency. J. Biomech. Eng. 128:527–39
Querzoli G, Fortini S, Cenedese A. 2010. Effect of the prosthetic mitral valve on vortex dynamics and turbu-
lence of the left ventricular flow. Phys. Fluids 22:041901
Querzoli G, Fortini S, Espa S, Costantini M, Sorgini F. 2014. Fluid dynamics of aortic root dilation in Marfan
syndrome. J. Biomech. 47:3120–28
Quill JL, Hill AJ, Laske TG, Alfieri O, Iaizzo PA. 2009. Mitral leaflet anatomy revisited. J. Thorac. Cardiovasc.
Surg. 137:1077–81
Rabbah JPM, Saikrishnan N, Siefert AW, Santhanakrishnan A, Yoganathan AP. 2013. Mechanics of healthy
and functionally diseased mitral valves: a critical review. J. Biomech. Eng. 135:021007
Rahimtoola SH. 2003. Choice of prosthetic heart valve for adult patients. J. Am. Coll. Cardiol. 41:893–904
Rajappan K, Rimoldi OE, Camici PG, Bellenger NG, Pennell DJ, Sheridan DJ. 2003. Functional changes in
coronary microcirculation after valve replacement in patients with aortic stenosis. Circulation 107:3170–75
Ramaswamy S, Boronyak SM, Le T, Holmes A, Sotiropoulos F, Sacks MS. 2014. A novel bioreactor for
mechanobiological studies of engineered heart valve tissue formation under pulmonary arterial physio-
logical flow conditions. J. Biomech. Eng. 136:121009
Rausch MK, Bothe W, Kvitting JPE, Swanson JC, Ingels NB Jr, et al. 2011. Characterization of mitral valve
annular dynamics in the beating heart. Ann. Biomed. Eng. 39:1690–702
Reul H, Talukder N, et al. 1981. Fluid mechanics of the natural mitral valve. J. Biomech. 14:361–72
Reynolds W, Hussain A. 1972. The mechanics of an organized wave in turbulent shear flow. Part 3. Theoretical
models and comparisons with experiments. J. Fluid Mech. 54:263–88
Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, et al. 2012. Heart disease and stroke statistics—
2012 update: a report from the American Heart Association. Circulation 125:e2
Sabbah H, Stein P. 1982. Effect of aortic stenosis on coronary flow dynamics: studies in an in-vitro pulse
duplicating system. J. Biomech. Eng. 104:221–25
Sacks MS, Merryman WD, Schmidt DE. 2009a. On the biomechanics of heart valve function. J. Biomech.
42:1804–24
Sacks MS, Schoen FJ, Mayer JE Jr. 2009b. Bioengineering challenges for heart valve tissue engineering. Annu.
Rev. Biomed. Eng. 11:289–313
Sacks MS, Sun W. 2003. Multiaxial mechanical behavior of biological materials. Annu. Rev. Biomed. Eng.
5:251–84
Saikrishnan N, Yap CH, Milligan NC, Vasilyev NV, Yoganathan AP. 2012. In vitro characterization of
bicuspid aortic valve hemodynamics using particle image velocimetry. Ann. Biomed. Eng. 40:1760–75
Salsac AV, Sparks S, Chomaz JM, Lasheras J. 2006. Evolution of the wall shear stresses during the progressive
enlargement of symmetric abdominal aortic aneurysms. J. Fluid Mech. 560:19–51
Sengupta P, Pedrizzetti G, Kilner P, Kheradvar A, Ebbers T, et al. 2012. Emerging trends in clinical assessment
of cardiovascular fluid dynamics. JACC Cardiovasc. Imaging 5:305–16
Shadden SC, Astorino M, Gerbeau JF. 2010. Computational analysis of an aortic valve jet with Lagrangian
coherent structures. Chaos 20:017512
Shortland A, Black R, Jarvis J, Henry F, Iudicello F, et al. 1996. Formation and travel of vortices in model
ventricles: application to the design of skeletal muscle ventricles. J. Biomech. 29:503–11
Simmons CA, Grant GR, Manduchi E, Davies PF. 2005. Spatial heterogeneity of endothelial phenotypes
correlates with side-specific vulnerability to calcification in normal porcine aortic valves. Circ. Res. 96:792–
99
Simon HA, Ge L, Sotiropoulos F, Yoganathan AP. 2010a. Numerical investigation of the performance of
three hinge designs of bileaflet mechanical heart valves. Ann. Biomed. Eng. 38:3295–310
Simon HA, Ge L, Sotiropoulos F, Yoganathan AP. 2010b. Simulation of the three-dimensional hinge flow
fields of a bileaflet mechanical heart valve under aortic conditions. Ann. Biomed. Eng. 38:841–53
Sotiropoulos F, Aidun C, Borazjani I, MacMeccan R. 2011. Computational techniques for biological fluids:
from blood vessel scale to blood cells. In Image-Based Computational Modeling of the Human Circulatory and
Pulmonary Systems, ed. KB Chandran, HS Udaykumar, JM Reinhardt, pp. 105–55. New York: Springer
Sotiropoulos F, Borazjani I. 2009. A review of state-of-the-art numerical methods for simulating flow through
mechanical heart valves. Med. Biol. Eng. Comput. 47:245–56
Sotiropoulos F, Yang X. 2014. Immersed boundary methods for simulating fluid–structure interaction. Prog.
Aerosp. Sci. 65:1–21
Stevanella M, Maffessanti F, Conti CA, Votta E, Arnoldi A, et al. 2011. Mitral valve patient-specific finite
element modeling from cardiac MRI: application to an annuloplasty procedure. Cardiovasc. Eng. Technol.
2:66–76
Stewart KC, Charonko JC, Niebel CL, Little WC, Vlachos PP. 2012. Left ventricular vortex formation is
unaffected by diastolic impairment. Am. J. Physiol. Heart Circ. Physiol. 303:H1255–62
Stolarski H, Gilmanov A, Sotiropoulos F. 2013. Nonlinear rotation-free three-node shell finite element for-
mulation. Int. J. Numer. Methods Eng. 95:740–70
Sun W, Martin C, Pham T. 2014. Computational modeling of cardiac valve function and intervention. Annu.
Rev. Biomed. Eng. 16:53–76
Le Gilmanov
Taylor CA, Figueroa C. 2009. Patient-specific modeling of cardiovascular mechanics. Annu. Rev. Biomed. Eng.
11:109–34
Tiederman W, Privette R, Phillips W. 1988. Cycle-to-cycle variation effects on turbulent shear stress mea-
surements in pulsatile flows. Exp. Fluids 6:265–72
Töger J, Kanski M, Carlsson M, Kovács SJ, Söderlind G, et al. 2012. Vortex ring formation in the left ventricle
of the heart: analysis by 4D flow MRI and Lagrangian coherent structures. Ann. Biomed. Eng. 40:2652–62
Van Rijk-Zwikker G, Delemarre B, Huysmans H. 1996. The orientation of the bi-leaflet CarboMedics valve in
the mitral position determines left ventricular spatial flow patterns. Eur. J. Cardio-Thorac. Surg. 10:513–20
van’t Veer M, van Straten B, van de Vosse F, Pijls N. 2007. Influence of orientation of bi-leaflet valve prostheses
on coronary perfusion pressure in humans. Interact. Cardiovasc. Thorac. Surg. 6:588–92
Veronesi F, Corsi C, Sugeng L, Caiani EG, Weinert L, et al. 2008. Quantification of mitral apparatus dynamics
in functional and ischemic mitral regurgitation using real-time 3-dimensional echocardiography. J. Am.
Soc. Echocardiogr. 21:347–54
von Knobelsdorff-Brenkenhoff F, Trauzeddel RF, Barker AJ, Gruettner H, Markl M, Schulz-Menger J. 2014.
Blood flow characteristics in the ascending aorta after aortic valve replacement: a pilot study using 4D-flow
MRI. Int. J. Cardiol. 170:426–33

Votta E, Le TB, Stevanella M, Fusini L, Caiani EG, et al. 2013. Toward patient-specific simulations of cardiac
valves: state-of-the-art and future directions. J. Biomech. 46:217–28
Wang Q, Sun W. 2013. Finite element modeling of mitral valve dynamic deformation using patient-specific
multi-slices computed tomography scans. Ann. Biomed. Eng. 41:142–53
Watton P, Luo X, Yin M, Bernacca G, Wheatley D. 2008. Effect of ventricle motion on the dynamic behaviour
of chorded mitral valves. J. Fluids Struct. 24:58–74
Weinberg EJ, Shahmirzadi D, Mofrad MRK. 2010. On the multiscale modeling of heart valve biomechanics
in health and disease. Biomech. Model. Mechanobiol. 9:373–87
Wong J, Göktepe S, Kuhl E. 2011. Computational modeling of electrochemical coupling: a novel finite
element approach towards ionic models for cardiac electrophysiology. Comput. Methods Appl. Mech. Eng.
200:3139–58
Yagi T, Yang W, Umezu M. 2011. Effect of bileaflet valve orientation on the 3D flow dynamics in the sinus
of Valsalva. J. Biomech. Sci. Eng. 6:64–78
Yap CH, Saikrishnan N, Tamilselvan G, Yoganathan AP. 2012. Experimental measurement of dynamic fluid
shear stress on the aortic surface of the aortic valve leaflet. Biomech. Model. Mechanobiol. 11:171–82
Yoganathan AP, Chandran K, Sotiropoulos F. 2005. Flow in prosthetic heart valves: state-of-the-art and future
directions. Ann. Biomed. Eng. 33:1689–94
Yoganathan AP, He Z, Jones SC. 2004. Fluid mechanics of heart valves. Annu. Rev. Biomed. Eng. 6:331–62
Yun BM, Dasi LP, Aidun C, Yoganathan A. 2014a. Computational modelling of flow through prosthetic heart
valves using the entropic lattice-Boltzmann method. J. Fluid Mech. 743:170–201
Yun BM, Dasi LP, Aidun C, Yoganathan A. 2014b. Highly resolved pulsatile flows through prosthetic heart
valves using the entropic lattice-Boltzmann method. J. Fluid Mech. 754:122–60
Yun BM, Wu J, Simon HA, Arjunon S, Sotiropoulos F, et al. 2012. A numerical investigation of blood damage
in the hinge area of aortic bileaflet mechanical heart valves during the leakage phase. Ann. Biomed. Eng.
40:1468–85
Zoghbi WA, Chambers JB, Dumesnil JG, Foster E, Gottdiener JS, et al. 2009. Recommendations for eval-
uation of prosthetic valves with echocardiography and Doppler ultrasound: a report from the American
Society of Echocardiography’s Guidelines and Standards Committee and the Task Force on Prosthetic
Valves, developed in conjunction with the American College of Cardiology Cardiovascular Imaging
Committee, Cardiac Imaging Committee of the American Heart Association, the European Association
of Echocardiography, a registered branch of the European Society of Cardiology, the Japanese Soci-
ety of Echocardiography and the Canadian Society of Echocardiography, endorsed by the American
College of Cardiology Foundation, American Heart Association, European Association of Echocardiog-
raphy, a registered branch of the European Society of Cardiology, the Japanese Society of Echocardiog-
raphy, and Canadian Society of Echocardiography. J. Am. Soc. Echocardiogr. 22:975–1014

Fluid Mechanics of Heart Valves and Their Replacements

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Fluid Mechanics of Heart Valves and Their Replacements

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FL48CH10-Sotiropoulos ARI 25 August 2015 14:11

Review in Advance first posted online

still occur before final publication

Fluid Mechanics of Heart

and Anvar Gilmanov2

Annu. Rev. Fluid Mech. 2016. 48:259–83 Keywords

This article’s doi: Abstract

Anatomy of the human heart The heart cycle

Pressure (mm Hg)

5 Left atrium Left ventricle pressure

The aortic valve, closed and open d Bileaflet mechanical e Bioprosthetic

www.annualreviews.org • Fluid Mechanics of Heart Valves 261

4. FUNDAMENTALS OF PULSATILE BLOOD FLOW IN THE HEART

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THE TRIPLE DECOMPOSITION

Ri j = −ρui u j = −ρ ũi ũ j − ρui u j ,

5. NATIVE VALVE HEMODYNAMICS

5.1. Mitral Valve

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improved understanding of MV hemodynamics is a critical prerequisite to bridge the gap between

6. PROSTHETIC VALVE HEMODYNAMICS

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6.1. Bileaflet Mechanical Heart Valves

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6.2. Trileaflet Flexible Valves

www.annualreviews.org • Fluid Mechanics of Heart Valves 273

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predictions of Leonardo da Vinci. Eur. Heart J. 35:1344

De Hart J, Peters G, Schreurs P, Baaijens F. 2003b. A three-dimensional computational analysis of ﬂuid–

vasc. Magn. Reson. 16:78

www.annualreviews.org • Fluid Mechanics of Heart Valves 279

valve leaﬂets by facilitating smooth closure. J. Thorac. Cardiovasc. Surg. 136:1528–35

www.annualreviews.org • Fluid Mechanics of Heart Valves 281

MRI. Int. J. Cardiol. 170:426–33

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