Applications in Engineering Science 10 (2022) 100094
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Applications in Engineering Science
journal homepage: www.sciencedirect.com/journal/applications-in-engineering-science
An engineering approach to mitral valve mechanics and function
Muath Bishawi a, b, Donald D. Glower a, *
a
Department of Surgery, Division of Cardiothoracic Surgery, Duke University Medical Center, Durham, NC, United States
b
Department of Biomedical Engineering, Pratt School of Engineering, Duke University Medical Center, Durham, NC 27710, United States
Glossary of abbreviations
MR mitral regurgitation
IMR ischemic mitral regurgitation
NIFMR nonischemic mitral regurgitation
NYHA New York heart association
Introduction
The mitral valve is but a very small part of the human body. It serves
a very simple mechanical function to allow blood to pass from the left
atrium into the left ventricle during diastole and to prevent blood from
flowing from the left ventricle into the left atrium during systole.
Because it is a purely mechanical structure, it lends itself very readily to
an engineering mechanics type of analysis. Furthermore, a number of
mitral valve related diseases can be evaluated and studied using an
engineering failure type framework such as the ones used to study
failure of mechanical components in machines (Tawancy et al., 2004). It
is an engineering marvel, withstanding enormous forces over 3 × 109
average number of cardiac cycles (Gunning and Murphy, 2015).
Failure of this structure, presenting as mitral valve dysfunction can
be fatal. Rheumatic heart disease which generally involves mitral ste­
nosis and/or regurgitation remains a leading cause of mortality globally
(Watkins et al., 2017). The most definitive treatment of mitral valve
disease usually involves mechanical repair or replacement of the mitral
valve, either surgically or using transcatheter techniques (Otto et al.,
2021). Surgical or transcatheter mitral valve repair or replacement
therefore inherently involves engineering science in the design of the
repair techniques, the design of the replacement prosthesis, and in de­
livery of the repair or replacement devices.
The purpose of this review is to touch on a few specific examples of
applied engineering science relevant to mitral valve function, dysfunc­
tion and treatments.
* Corresponding author.
E-mail address: glowe001@mc.duke.edu (D.D. Glower).
https://doi.org/10.1016/j.apples.2022.100094
Received 25 January 2022; Accepted 6 March 2022
Available online 8 March 2022
2666-4968/© 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
Structural components of the mitral valve
The mitral valve can be broken into 4 main components with each
serving unique functions and having distinctive material properties. The
leaflets, the annulus, the chords and papillary muscles (Fig. 1- Mathe­
matical model of MV). The forces encountered are different for each of
these unique components with specific modes of failure leading to mitral
valve disease. For instance, the chords must deal with axial tensile forces
during systole without elongation (a form of deformation resulted by
such forces). If the chordal strength is decreased or the overall applied
load is increased this will lead to deformation (chordal rupture or
elongation) which in turns leads to mitral regurgitation. In fact, one can
then link the mechanical failures of the different mitral valve compo­
nents with the associated widely adopted Carpentier’s functional clas­
sifications (Fig. 2-Carpentier’s Classification) of the mitral regurgitation
that will result (Carpentier et al., 2010). While there are individual
differences associated with body surface area and gender, there are
accepted average ranges of certain parameters such as chordae length or
leaflet thickness. Factors leading to failure of these components can
therefore be studied by evaluating changes for the norm and their
associated effect on overall mitral valve function (Table 1).
Chordae tendineae (chords)
An important part of the sub-mitral apparatus, Chordae tendineae
are bands fibrous tissue that attach the edge of the mitral valve to an
anchor point on the papillary muscle of ventricular wall. They must
tolerate a certain amount of stress (σ, which is the net force on the chord
divided by the cross sectional area) during ventricular ejection, during
each cardiac cycle. The Strain (response of chord to the applied stress)
must be within a certain limit to allow the chord to continue to function
normally (Hearn, 1997). The longitudinal forces applied on each chord
during the cardiac cycle, causes a specific amount of stress on each chord
leading to change in the amount of tension and small changes in length
of the chords. The chords are able to handle a certain amount of stress at
a time, where beyond that limit, the yield strength of the chords is
M. Bishawi and D.D. Glower
exceeded, leading to their failure. In normal physiology, the amount of
stress applied to the chords during systole is small, and the chords return
to their normal length when the force is removed (diastole). This normal
cycle can be referred to as elastic deformation, since the cords return to
their original state. However, if the stresses are higher beyond the elastic
limit of the chord, this would lead to plastic deformation of the chord,
where the chords remain in a deformed state even after the stress is
removed. A good example of this would be chordal elongation and
chordal rupture.
Human chords have a striped pattern 11 μm in width, with an un­
dulating pattern of collagen fibers arranged in bundles around the entire
circumference of each chord. This collagen pattern allows for the
impressive elasticity that the chords must have to deal with the cardiac
cycle over many years (Ritchie et al., 2006). During papillary muscle
contraction, the collagen straightens as the force stretches the chord.
During diastole, the collagen is returned to its wavy baseline configu­
ration. With aging or in disease states where the chords are subjected to
higher stress, there is elongation of the wave pattern of the collagen
during the relaxed state (Millington-Sanders et al., 1998). Furthermore,
the overall stress is additionally increased as the cross-sectional area is
reduced. Eventually this process leads to chordal rupture.
There are multiple types of chords (a) commissural chordae insert
into and define the commissures between the leaflets, (b) rough zone
chordae insert into the ventricular aspect of the distal rough portion of
the leaflets- typically trifurcating when inserting into the leaflets, (c)
strut chordae- anterior leaflet rough zone chordae that are thicker than
the others, and finally, (d) cleft chordae insert into the clefts between the
scallops of the posterior leaflet, and finally (e) basal chordae from the
posterior ventricular wall and insert into the basal zone of the posterior
leaflet (Lam et al., 1970).
There are individual to individual differences in the pattern of the
chordal branching network. Little to no work as looked at different
branching patterns as predictors in developing MR long term, in large
part due to difficulty getting good imaging of the chordal branching
patterns. However, mathematical simulation studies have shown that
Fig. 1. Mechanical behavior of the 4 major components of the mitral valve can be studied and modeled. Modes of failure can then be evaluated. (Adopted with
permission from Park et al. 2019).
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Applications in Engineering Science 10 (2022) 100094
different branching patterns can have variable force distribution across
the chords, with some having to withstand very high forces that might
increase the risk of chordal failure (Park et al., 2019) (Fig. 3).
Using this stress-strain relationship, one can calculate Young’s
module or the modulus of elasticity for mitral chords (Zukor, 1960).
Comparison of Young’s module changes across different scenarios helps
in improving our understanding of the function of the mitral valve
chords during different disease states (Wilcox et al., 2014a). Impor­
tantly, using this technique has been instrumental in better defining
chordal preservation and transfer strategies for mitral valve repair, since
there are important differences between primary, secondary and tertiary
chords. It has also help set design parameters for artificial chords taking
into account important variables such as diameter and frequency
dependent viscoelastic properties of healthy mitral valve chords (AG
Wilcox et al., 2014b). In one study, chordae tendineae of the mitral valve
from young (18–26 weeks) and old (over 2 years) porcine hearts were
studied (Millard et al., 2011). For chordae from the posterior leaflet of
the valve, the Young’s modulus values were significantly higher for the
thinner marginal chordae (59 ± 31 MPa young; 88 ± 21 MPa old) than
for the thicker basal chordae (31 ± 4 MPa young; 28 ± 9 MPa old).
Marginal chordae (both anterior and posterior) had significantly higher
value for their Young’s modulus in old (88 ± 21 MPa anterior and
posterior) than in young (62 ± 17 MPa anterior, 59 ± 18 MPa posterior)
pig hearts (Millard et al., 2011).
Changes in the tissue properties of the mitral valve also have an
important effect on the mechanical properties of the chords. In one
study, Chordae from 24 normal and 59 myxomatous mitral valves were
cut into 10 mm-long segments and mechanically tested to measure
extensibility, modulus, failure stress, failure strain, and failure load
(Myxomatous mitral valve chordae, 2021). Chordae from myxoid mitral
valves were larger (1.9 ± 0.1 mm2 versus 0.8 ± 0.1 mm2), heavier (16.6
± 1.0 mg versus 6.5 ± 0.4 mg), had lower moduli (40.4 ± 10.2 MPa
versus 132 ± 15 MPa), failed at significantly lower tensile stress (6.0 ±
0.6 MPa versus 25.7 ± 1.8 MPa, p ≤ 0.001) and absolute load (728 ± 50
g versus 1450 ± 135 g).
M. Bishawi and D.D. Glower Applications in Engineering Science 10 (2022) 100094

Using this understanding, one can then target chord repair strategies Table 1
to be most effective in reducing MR, and increasing the likelihood of Mechanical properties of the main mitral valve structures, and associated
long term durability. For instance, the location of placing new chords on functional classification associated with their failure.
the leaflet and on the papillary muscles can have important differences Parameter Average Changes during Carpentier’s Functional
in the forces that these chords must withstand during the cardiac cycle. values diseases Classification
One study looked specifically at anchoring Neochordae (ePTFE) to the Diameter of 20–40 mm Dilation Type I
left ventricular apex compared to a papillary muscle base, or the tip annulus
(Sadri et al., 2021). The location of the chords on the mitral valve P2 Leaflet thickness 4 mm increased Type IIIa
Distance between 22 mm Increased Type IIIb
leaflet was also varied between central, medial or lateral. The study
pap muscles
demonstrated that the overall forces were higher for P2 medial attach­ Chordae Length 15–19 mm Elongated or Type II
ments compared to the lateral or medial P2 attachments regardless of restricted
the anchoring location (Sadri et al., 2021). Chordae Stiffness .06 N/mm Decreased or Type II
Insights into the mechanical properties of the mitral chords has been increased

the foundation of a number of innovative technologies aims at chordal

replacement strategies for mitral repair (Savic et al., 2018; Seeburger
et al., 2014). Force-sensing neochords have also been developed and
tested to better understand the influence of different factors such as
ventricular pressure, systemic pressure etc. on the forces exerted on
different chords (Paulsen et al., 2020). Overall, these developments will
open the door to real time assessment of chordal tension during neo­
chord implantation to optimize the repair on a beating heart (Grinberg
et al., 2019). These strategies will help decrease the variability in the
outcomes seen with neochord implantation strategies- mainly attributed
to the technical difficulty of determining optimal chordal position and
length on a non beathing, arrested heart (Di Bacco et al., 2020). While it
is still early to say whether such data will be important in improving
repair durability, it provides a promising avenue to further improve
mitral valve repair efficacy.
Leaflets
Similar to the variability found in chord anatomy, there is important
individual to individual variability in leaflet anatomy (Quill et al.,
2009). Furthermore, the transition zone between the chordal attach­
ments to the mitral valve have unique mechanical properties with
important consequences on the stress distribution during the cardiac
cycle (Chen et al., 2004).
Both mitral valve leaflets are stiffer in the circumferential direction
than in the radial direction (Pham and Sun, 2014), with the anterior
leaflet being stiffer than the posterior. As the leaflets get more calcified
with aging or in hypertension, the stiffness increases and strain de­
creases (Pham and Sun, 2014). These changes also have important
consequences to regional variations of the dynamic stiffnesses seen with
normal mitral leaflets (Baxter et al., 2017).
Further changes in the material properties of the leaflets are also seen
with myxomatous mitral disease. Myxomatous leaflets are more exten­
sible (41.2% ± 18.5% vs 17.3% ± 6.7%) and less stiff (4.0 ± 1.6 vs 6.1
± 1.4 kN/m), but had similar leaflet strength (Barber et al., 2001).
Interestingly, compared with normal valves, myxomatous valves have

Fig. 2. Carpentier’s Functional classification of MR.

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M. Bishawi and D.D. Glower Applications in Engineering Science 10 (2022) 100094

Fig. 3. Different branching patterns demonstrating variations in stress distribution. Some branching patters are associated with high forces on certain chords that
might cause early failure in the form of chord elongation or rupture. (Adopted with permission from Park et al. 2019).

Fig. 4. Stress distributions across the MV leaflets and annulus at peak systole before vs after repair.(A) Stress distributions prior to and following virtual posterior
leaflet resection, (B) Average stress values in six sub-regions of the MV leaflets. (Creative commons).

4
M. Bishawi and D.D. Glower
more differences in material properties of the chordae than of the leaf­
lets (Barber et al., 2001).
Classic mitral valve repair techniques involve resecting portions of
the mitral valve leaflets (Suri and Orszulak, 2005). Such resection can
dramatically alter the geometry and function of the valve, which in turn
can be evaluated using computational modeling to better understand
their effects on mitral valve mechanics. For instance, quadrangular
resection with ring annuloplasty for degenerative mitral valves is a
common repair technique used widely by clinicians for repair of the
mitral valve (Fedak et al., 2008). Using 3D computer simulation from
patient specific 3D echo data sets, annular motion and physiologic
transvalvular pressure gradient can be evaluated. Advances in 3D echo
and computer simulation can therefore be used to better understand pre
and post repair stress distribution across the leaflets to better plan sur­
gical repair on more complex lesion, and to improve repair technique to
increase durability of such repair (Rim et al., 2015) (Fig. 4).
Influence of ventricular mechanics on mitral function
Normal myocardial tissue and the mitral valve annulus are generally
elastic (Ghista and Sandler, 1969). In the failing ventricle however, the
ventricular wall and mitral annulus become more plastic than elastic
(Gaasch et al., 2008). Thereby, forces on the ventricle or mitral annulus
can change annular size in a way that does not return to baseline once
those distracting forces are removed. This may be the major reason that
mitral annular fixation during mitral repair. Mitral regurgitation severe
enough to warrant surgical or interventional repair is almost always
associated with congestive heart failure and secondary changes in ma­
terial properties (Bishawi et al., 2021a2021b; Bishawi and Glower,
2021). Altered material properties of the ventricle then lead to abnormal
ventricular geometry which can significantly impact mitral valve func­
tion. The mitral valve sits in the inflow orifice of the left ventricle, and
the chords are attached to the ventricular walls. Thus left ventricular
dilation will result in dilation of the mitral annulus and distraction of the
two mitral leaflets apart to where they no longer coapt, causing mitral
regurgitation (Carpentier et al., 2010) (Fig. 1, Carpentier type I) Table 1.
The normal mitral valve has roughly 3 to 10 mm of coaptation be­
tween the two leaflets to create a seal during systole. Left ventricular
dilation also pulls the mitral chords downward into the ventricle and
displaces them laterally, limiting closure of the leaflets and again pro­
ducing regurgitation. This is termed the Carpentier type IIIB mitral valve
dysfunction or leaflet restriction during systole (Carpentier et al., 2010).
When the edges of the mitral leaflets are displaced downward into the
ventricle during systole, the effective leaflet height from the annulus to
the coaptation point is effectively shortened. (Fig. 4) In effect, the side of
a triangle (effective leaflet height) is always less that the hypotenuse
(true leaflet height). As result, mitral annuloplasty in type IIIB restricted
mitral valves can be treated using an undersized annuloplasty ring, by
extending leaflet height with a leaflet patch, or by reorienting the
papillary muscles to produce the systolic restriction (Bishawi and
Glower, 2021) (Fig. 4).
In addition to closing during systole, the mitral valve apparatus also
serves to attach the mitral annulus and the base of the heart to the
ventricular apex (Brecker, 2000). This connection through the mitral
tissue effectively improves the ability of the heart to shorten in the
longitudinal axis, thereby improving contractility relative to absence of
the mitral valve apparatus. Furthermore, the mitral apparatus carries
some mechanical load during systole, reducing wall stress in the longi­
tudinal axis during systole, and minimizing the likelihood of mechanical
rupture of the ventricular free wall during systole (Deniz et al., 2008).
Surgical removal of the posterior leaflet and chords in particular is
associated with loss of the ventricular contractility and increased risk of
the ventricular free wall rupture (Karlson et al., 1988).
Another importance of these attachments relate to the vortex pat­
terns and energy loss in left ventricular flow that is seen when the mitral
leaflets are not preserved during mitral valve replacement. Compared to
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Applications in Engineering Science 10 (2022) 100094
repair, mitral valve replacement alters the intraventricular vortex
pattern and increases flow energy loss (Akiyama et al., 2017).
The normal mitral annulus contracts during systole and dilates
during diastole to facilitate blood flow into the ventricle and to facilitate
contraction of the base of the heart to achieve systolic ejection. Any
disease or appliances making the mitral annulus rigid can thereby cause
some degree of mitral orifice stenosis. Annular fixation can also impair
the ventricular contractility due to less contraction of the base of the
heart. On the other hand, in a dilated ventricle, reducing annular
diameter with an undersized prosthesis in an abnormally dilated
annulus can effectively reduce wall stress in the base of the heart and the
chords (Wong et al., 2012).
In hypertrophic cardiomyopathy with an abnormally narrow left
ventricular outflow tract, blood flow velocities during systole can be
sufficient to suck the anterior leaflet of the mitral valve up against the
interventricular septum by the Venturi effect, effectively obstructing the
ventricular outflow tract during systole (Walker et al., 2012). This is
known as systolic anterior motion of the mitral valve or SAM. Because
stroke volume must be maintained to perfuse the body, treatment of this
problem is to enlarge the ventricular outflow track diameter during
systole, thereby reducing the Venturi effect. This can be achieved either
surgically with septal myectomy, transcatheter alcohol ablation of the
interventricular septum, by pharmacologic reduction of ventricular
contractility, or by improving ventricular volumes with volume
infusion.
Another strategy to address SAM is to attach the anterior and pos­
terior leaflets together, usually in the center, to effectively create two
orifices (Timek et al., 2004). This technique was originally conceived by
an Italian surgeon, Dr. Alfieri and is known as the edge to edge repair
technique or the Alfieri stitch (Timek et al., 2004). A transcatheter
version of this technique is now available through several manufac­
turers, with the original device called MitraClip (Siegel et al., 2011).
From geometry and fluid mechanics, an edge to edge mitral repair
inherently reduces the diastolic mitral orifice by about 50% (Maisano
et al., 1999). A diastolic mitral orifice under 2 cm2 in the average adult is
considered to be mitral stenosis. Therefore the edge to edge to repair is
not applicable unless the starting orifice is 4 cm2 or greater (Carpentier
et al., 2010).
Transcatheter mitral repair techniques have been most successful
with transcatheter duplication of the Alfieri stitch. Delivery and imaging
with the trans septal approach remain the greatest challenges. Despite
over 10 years of experience with the transcatheter MitraClip, other
transcatheter mitral repair devices remain elusive. Other investigational
transcatheter mitral repair devices provide annular fixation or chordal
replacement have had difficulties with imaging, delivery, and obtaining
a durable repair (Hensey et al., 2021).
As above with type IIIB functional mitral regurgitation, the distance
from the interventricular septum to the posterior ventricular free wall is
critical relative to restoring coaptation of the restricted mitral valve. Any
central edge to edge repair will reduce the radius of curvature of the two
new orifices to 50% that of the original valve, effectively reducing the
circumferential stress to produce annular dilation (Vitarelli et al., 2015).
Thus, an edge to edge mitral repair may partially stabilize mitral annular
diameter, despite lack of an annular stabilizing ring or appliance.
Transcatheter MitraClip is most commonly used in functional mitral
regurgitation type IIIB, and very stable results out to 5 years have been
well-documented (Lesevic et al., 2017).
Another interesting engineering aspect of the edge to edge double
orifice repair of the mitral valve, whether surgical or transcatheter, is
that, if the edge to edge connection is off center, two new orifices of
differing size result. By definition, the gradient across each of those two
orifices has to be the same. However, the flow velocity in the small
orifice will tend to be greater than that in the larger orifice (Sargordi
et al., 2020). With current technology, echocardiography is most
commonly used to estimate transvalvular gradients during diastole.
Because echocardiography can only measure flow velocity, a double
M. Bishawi and D.D. Glower Applications in Engineering Science 10 (2022) 100094

orifice valve of two different sizes can result in a double velocity
waveform (Caballero et al., 2020) (Fig. 5). The majority of flow will be
through the larger orifice with a lower blood flow velocity, suggesting
that the lower flow velocity line it would be the most accurate to assess
the mitral valve gradient in that situation (Silvestry et al., 2007). This is
a real world illustration that the simplified Bernoulli equation with only
one term can yield inaccurate results when flow velocities and turbu­
lence are great enough to make the other 3 terms of the full Bernoulli
equation significant.
Mitral prosthesis engineering
Engineering a mitral prosthesis is much more complex than devel­
oping an aortic valve prosthesis. This is illustrated by the fact that simply
implanting an ABO unmatched aortic valve from a human donor (ho­
mograft or allograft) works quite well for aortic valve replacement.
These nonviable and unmatched human tissue transplants have dura­
bility in the 10 to 15 years range have been used for over 60 years. On
the other hand, attempts to transplant a human mitral valve into another
verse recipient have resulted in frequent failures (Olivito et al., 2012).
This may result in part from the fact that the normal aortic valve has
only about 8 proteins, while the normal mitral valve has over 200 pro­
teins that can be measured. Thus rejection of the mitral allograft is much
more likely. In addition, reattaching a mitral valve is more complicated
with reattachment to the annulus and reattachment of the papillary
muscles in the proper geometry all being necessary. Whereas, the aortic
valve with a tubular annulus can be very easily loaded onto a stent on a
balloon and delivered as what is now known as transcatheter aortic
valve replacement (Dasi et al., 2017). Transcatheter mitral valve
replacement has struggled with many design issues (Enta and Naka­
mura, 2021). Transcatheter mitral replacement issues include obstruc­
tion of the left ventricular outflow tract, avoiding perivalvular leak from
the plastic non-tubular mitral orifice, and not becoming entangled in the
complex native mitral valve leaflets and chords (Fedak et al., 2008;
Webb et al., 2019; Vaquerizo et al., 2015; Inderbitzin et al., 2016). A
number of simulators have been used to compare flow characteristics of
different mitral valve replacement options, and will likely to continue to
play an important role in testing different transcatheter mitral specific
valvular solutions as they become available (Jimenez et al., 2005).
Conclusions
The mitral valve is a complex mechanical structure serving a me­
chanical function in an even more complex fluid pump known as the
human heart. Measurable abnormalities in the material properties or
geometry of the mitral valve are associated with significant human

Fig. 5. Velocity streamlines during peak diastole. Marked differences in the inflow flow structure and magnitude were observed pre- and post-clip (pink), as well as
between the different clip/ring configurations. Clip implantation significantly altered the intraventricular hemodynamics by creating a multiple-jet flow due to the
double-orifice MV for the lateral and central clip models, and the triple-orifice MV for the double clip models. Moreover, the post-clip jets were not oriented toward
the apex, but toward the LV wall where they impinged, leading to higher near-wall velocities than the pre-clip state, especially for the clip models with a ring.
(Creative commons).

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M. Bishawi and D.D. Glower Applications in Engineering Science 10 (2022) 100094

disease. Ultimately, mitral valve disease can be better understood and Inderbitzin, D.T., Taramasso, M., Nietlispach, F., Maisano, F., 2016. Mitral valve repair
versus replacement: is it a different story for percutaneous compared to surgical
ultimately better treated by applying engineering material science and
valve therapy? J. Cardiovasc. Surg. 57 (3), 410–420 (Torino). https://pubmed.ncbi.
fluid mechanics. nlm.nih.gov/27035893/. Accessed January 4, 2022.
Jimenez, J.H., Soerensen, D.D., He, Z., Ritchie, J., Yoganathan, A.P., 2005. Mitral valve
External funding function and chordal force distribution using a flexible annulus model: an in vitro
study. Ann. Biomed. Eng. 33 (5), 557–566. https://doi.org/10.1007/S10439-005-
1512-9, 2005 335.
None Karlson, K.J., Ashraf, M.M., Berger, R.L., 1988. Rupture of left ventricle following mitral
valve replacement. Ann. Thorac. Surg. 46 (5), 590–597. https://doi.org/10.1016/
S0003-4975(10)64712-1.
Declaration of Competing Interest Lam, J.H., Ranganathan, N., Wigle, E.D., Silver, M.D., 1970. Morphology of the human
mitral valve. I. Chordae tendineae: a new classification. Circulation 41 (3), 449–458.
The authors declare that they have no known competing financial https://doi.org/10.1161/01.CIR.41.3.449.
Lesevic, H., Karl, M., Braun, D., et al., 2017. Long-term outcomes after mitraclip
interests or personal relationships that could have appeared to influence implantation according to the presence or absence of EVEREST inclusion criteria.
the work reported in this paper. Am. J. Cardiol. 119 (8), 1255–1261. https://doi.org/10.1016/J.
The authors declare the following financial interests/personal re­ AMJCARD.2016.12.027.
Maisano, F., Redaelli, A., Pennati, G., Fumero, R., Torracca, L., Alfieri, O., 1999. The
lationships which may be considered as potential competing interests: hemodynamic effects of double-orifice valve repair for mitral regurgitation: a 3D
computational model. Eur. J. Cardiothorac. Surg. 15 (4), 419–425. https://doi.org/
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