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Computer Methods and Programs in Biomedicine 213 (2022) 106506

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Computer Methods and Programs in Biomedicine


journal homepage: www.elsevier.com/locate/cmpb

Left atrial appendage shape impacts on the left atrial flow


hemodynamics: A numerical hypothesis generating study on two cases
Lida Alinezhad a, Farzan Ghalichi a, Majid Ahmadlouydarab b,∗, Maryam Chenaghlou c
a
Department of Biomedical Engineering, Division of Biomechanics, Sahand University of Technology, Tabriz, Iran
b
Faculty of Chemical & Petroleum Engineering, University of Tabriz, Tabriz, Iran
c
Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

a r t i c l e i n f o a b s t r a c t

Article history: Background and objectives: The left atrial appendage (LAA) is the most common region for thrombus
Received 31 October 2020 formation in atrial fibrillation (AF). Morphological parameters such as shape, size, and LAA volume can
Accepted 25 October 2021
cause insufficient effectiveness of available therapeutic options. This study aimed to examine blood flow
inside LAA and its removal effects. Computational fluid dynamic (CFD) simulations were carried out on
Keywords: two patients with different morphologies.
Left atrial appendage Methods: Two patients’ CT was used to reconstruct the 3D geometries of the left atrium (LA) and left
Shape and volume atrial appendage (LAA). Then, the geometries were refined in the mentioned software, and the LAA in
Atrial fibrillation some models was removed. Next, in generated 3D volume mesh, sinus rhythm (SR) and atrial fibrillation
CFD simulation
(AF) outflow velocity were imposed at the mitral valve as boundary conditions. Finally, CFD simulation
Thrombus formation
was conducted to analyzing blood flow within LA with/without LA.
Results: The results confirmed that velocity and vorticity decreased under AF conditions inside the LA
domain for both patients. However, removing LAA may cause unpredictable consequences, due to dif-
ferent shape and volume of LAA. LAA removal had insignificant effects on velocity and vorticity within
LA in SR-mitral outflow. However, removing LAA increased the blood flow rate by 9.15% and vorticity by
7.27% for patient one under AF rhythm (SR)-outflow. In contrast, for patient two, LAA removal in both
AF and SR decreased velocity and vorticity within the LA domain. In SR-mitral outflow, velocity dropped
by 18.8 %, and vorticity by 13.2%. Also, under AF velocity and vorticity decreased by 23.33% and 18.6%
respectively. Meanwhile, the results indicated that the vorticity magnitude increased inside the LAA un-
der AF associated with the risk of thrombus formation, particularly for patient one under AF. The distal
part of LAA in both patients was the most common region for blood stasis because of the lowest velocity
magnitude.
Conclusion: Overall, the morphology of LAA could be the critical parameter to determine the possibility
of thrombosis formation, particularly under AF conditions. High volume, low blood flow velocity and
two-lobe-appendage are more likely to have blood stasis. Furthermore, the morphology difference can
affect the LAA removal result and make it more complicated. So, it could be challenging to generalize
LAA removal as a therapeutic option for different patients. The implication of this CFD observation needs
more investigation.
© 2021 Elsevier B.V. All rights reserved.

1. Introduction four main types: Chicken Wing is the most prevalent (48%), fol-
lowed by Cactus shape (30%), with a dominant central lobe and
The left atrial appendage (LAA) originates from the left atrium secondary lobes extending from the main lobe in both superior
and develops during fetal growth [1]. Anatomical and morpho- and inferior directions; Wind Sock (19%) has one dominant lobe;
logical studies illustrate the LAA as a long, tubular, and hooked and Cauliflower (3%) with a complex internal shape [2]. LAA mor-
structure with variations in size, shape, and volume. Recent stud- phology, size, and volume make it hard to estimate its effect on
ies based on computed tomography (CT) categorized the LAA into left atrial flow. Recent studies reveal that LAA is the most preva-
lent region for thrombosis, also increases the risk of stroke in pa-
tients with atrial fibrillation (AF) [3–5]. Atrial fibrillation (AF) is

Corresponding author. an electrophysiological pathology with irregular atrial beats and
E-mail address: mahmadlouydarab@tabrizu.ac.ir (M. Ahmadlouydarab). is known as the most common cardiac arrhythmia that augments

https://doi.org/10.1016/j.cmpb.2021.106506
0169-2607/© 2021 Elsevier B.V. All rights reserved.
L. Alinezhad, F. Ghalichi, M. Ahmadlouydarab et al. Computer Methods and Programs in Biomedicine 213 (2022) 106506

the rate of mortality and morbidity [6,7]. Atrial fibrillation is as- higher in SR than in AF. Fluid particles observation after three car-
sociated with valvular heart diseases such as aortic stenosis and diac cycles revealed that AF could increase the risk. Their studies
mitral stenosis, especially mitral regurgitation [8,9]. Undergoing AF demonstrated that low quantities of vorticity and velocity carry a
can cause electrical, structural, and contractile remodeling [10–13]. higher risk of thrombosis. Simple morphologies showed an equal
Atrial enlargement, LA malfunction, and insufficient atrial contrac- or even higher risk of thrombus formation than complex ones.
tion lead to thrombus formation, predominantly in the LAA [3,14]. More recently, Wang et al. (2020) performed a patient-specific CFD
Although the location of atrial thrombus in subjects with AF can simulation based on the same boundary conditions as Bosi et al.
differ, the LAA cavity is the most common region for thrombus used (the same mitral outflow and the rigid LA wall). Their study
in patients with non-valvular AF [15]. Blood stagnation commonly showed that thrombosis begins to form on the LAA wall and then
occurs in the LAA, where blood flow velocity drops dramatically expands toward the internal domain of LAA [35]. Also, Fanni et al.
[1,5,13]. So, LAA has recently gained attention as a therapeutic tar- (2020) conducted CFD simulation on different LAA shapes with a
get in predicting thrombosis, especially in AF patients. There are rigid wall assumption. Their results showed that LAA orifice area
several ways to prevent thrombus, including oral anticoagulants, and low velocity in the Cauliflower and Cactus shapes were associ-
LAA occlusion, or LAA removal during valve surgery [1,13]. Al- ated with thrombogenicity [36]. Then, Villalba et al. (2021) con-
though drug therapy can prevent blood stasis, it has a high risk sidered six patients with different atrial functions, three with a
of bleeding complications. Also, Surgical closure of the LAA can history of LAA thrombus or transient ischemic attacks, and three
fail in some patients [16,17]. Though several clinical treatments without thrombus [37]. They compared the rigid wall and moving
have been proposed to decrease the risk of thrombus formation wall results and showed LA wall motion could affect hemodynamic
in the LAA, studies have shown that there is still ongoing risk in parameters, particularly patients with intermediate residence time.
some patients [1,13,16,18]. These methods could fail due to the Also, they found that LA wall function had an impact on LAA’s clot.
different morphological parameters like shape, size, and LAA vol- Unfortunately, despite all the studies mentioned earlier, there is
ume. Researchers have identified hemodynamic parameters, such a lack of knowledge about LAA shape impacts on blood flow pa-
as velocity, vorticity, and shear stress, as indicators of thrombo- rameters inside LA and LAA; and how LAA removing affects the
sis [19,20]. So far, different techniques have been used to assess blood flow. So, in the current numerical study, first and foremost,
blood flow within the left atrium. A transesophageal echocardio- we aim to assess the removal of LAA effects on the blood flow in
gram (TEE) is frequently used in clinical practice to assess flow ve- LA in patients with different geometries and two mitral outflow
locity and assess blood stasis in the LAA and LA. However, TEE can- profiles. Second, we will analyze hemodynamic parameters in dif-
not accurately monitor hemodynamic parameters within the small ferent LAA morphologies that contribute to blood stasis.
region [21,22]. Indeed, TEE is an invasive procedure. 4D MRI is a
cutting-edge technology in clinical research to provide more de- 2. Methods
tailed information about the 3D blood flow during the cardiac cy-
cle. However, resolution limitations make it challenging to capture These studies included eight models under different conditions.
blood flow parameters accurately. Additionally, the scan time is rel- In some models, the left atrial appendage was removed to show its
atively long [23,24]. Today, computational modeling can provide a effects on the left atrial blood flow. The CFD simulations were con-
comprehensive understanding of the AF mechanisms and conse- ducted for two different outflows on the mitral valve; sinus rhythm
quences [25,26]. Personalized computational models can provide (SR) and atrial fibrillation (AF). Table 1 shows information for each
fibrosis modeling, atrial fiber orientation, wall thickness hetero- prepared model. It is worth mentioning that models 1 to 4 con-
geneity impacts on AF within realistic geometry and tissue prop- tribute to patient 1 (Male, 58-year-old), and Models 5 to 8 are re-
erties [27,28]. Computational fluid dynamics (CFD) can give more lated to patient 2 (Male, 50-year-old).
quantitative information about blood flow and assess thrombosis
risk [29]. It also allows evaluating blood flow in small regions con- 2.1. Image processing
taining the lobes of LAA. Some CFD simulations have been done in
different LAA morphologies to analyze hemodynamic parameters Fig. 1 shows 3D patient-specific models with different LAA mor-
and thrombus formation risk. Otani et al. (2016) developed a CFD phologies based on CT images. Data characteristics include the fol-
framework to perform blood flow analysis, considering patient- lowing:
specific LA wall motion [30]. Their studies showed that computa- Patient 1; The image resolution is 512∗ 512∗ 239; the in-plane
tional methodology could help understand intracardiac thrombo- pixel size is 0.369 mm ∗ 0.369 mm; the slice thickness is 0.6 mm,
sis and stroke in individual patients with LA structural remodeling. and the slice gap is 0.6 mm.
Also, despite lower kinetic energy, the subject with relatively sim- Patient 2; The image resolution is 512∗ 512∗ 295, The in-plan
ple LAA morphology may be less prone to stroke than the other pixel dimensions size 0.349 mm ∗ 0.349 mm, the slice thickness
with a more complex morphology [30]. Next, Bosi et al. (2018) 0.75 mm, and the slice gap 0.5 mm.
established a CFD simulation in different morphology with rigid The 3D geometry of the patients was reconstructed using the
wall assumption for the LA movement [31]. They showed the risk CT Heart Segmentation and Seed Point Detection method (Mimics
of thromboembolism in LAA with cauliflower shape is higher than Medical 21.0 Software). Then, pulmonary vein bifurcations were re-
that of others. Jia et al. (2019) proposed a CFD framework to pre- moved, and the geometries improved by using 3-Matic 11 Research
dict the LAA closure impacts in one particular patient, considering software. Also, LAA was removed in some models (Table 1). The
a rigid LA wall [32]. Their results confirmed that the velocity mag- surfaces were made on LA in Geomagic Design X. Software. Next,
nitudes dropped dramatically to almost zero in the distal part of the geometries were transferred to SOLIDWORKS software to cor-
the LAA. Additionally, after LAA occlusion, vortices are reduced in rect the broken faces and merge the surfaces. Also, the inlets and
size, strength, and number. Masci et al. (2019, 2020) used the CFD outlet surfaces were defined in SOLIDWORKS software. Eventually,
simulation approach on two cases under AF and SR to estimate the geometries were imported into ANSYS WORKBENCH. To reduce
thrombus formation risk [33]. Also, they developed a workflow to the entrance effects, the entrance lengths were extended in ANSYS
investigate LAA morphology’s impacts on LA blood flow by con- GEOMETRY. To set up the simulation, 3D patient-specific models
sidering the wall motion in another study [34]. Under AF, loss of were meshed by using ANSYS Meshing. Different mesh sizes were
LAA contractility may contribute to blood stasis. Furthermore, the constructed for meshing convergence examination, and the final
mean blood flow velocity in the LAA during the cardiac cycle was meshes described here are the optimal meshes with high without

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L. Alinezhad, F. Ghalichi, M. Ahmadlouydarab et al. Computer Methods and Programs in Biomedicine 213 (2022) 106506

Table 1
Properties of the models.

Model number LA Volume (ml) LAA Volume (ml) LAA Orifice Area (mm2 ) LAA lobe Total Element Number

Model 1 (SR) 118 9.08 305.5 2 761750


Model 2 (SR) 113.47 Removed - - 734245
Model 3 (AF) 118 9.08 305.5 2 761750
Model 4 (AF) 113.47 Removed - - 734245
Model 5 (SR) 70.635 4.74 296.1 1 531401
Model 6 (SR) 68.22 Removed - - 503758
Model 7 (AF) 70.635 4.74 296.1 1 531401
Model 8 (AF) 68.22 Removed - - 503758

Fig. 1. Shape of LAA in two selected patients.

compromising solution accuracy. Fig. 2 illustrates the reconstruc- left atrium and the left ventricle (LV). A-wave happens at the end-
tion of geometry for one of the patients. Each model was subjected diastolic phase and associates with LA contraction. As shown in
to this procedure. Fig. 3(a), in sinus rhythm, both E- and A- waves occur during the
cardiac cycle’s systolic phase. However, in Fig. 3(b) with atrial fib-
2.2. Flow Simulation rillation, the A-wave was disappeared due to insufficient atrial con-
traction. The transmitral velocity profiles and the E/A peak veloc-
In the present study, flow simulations were conducted us- ity show diastolic function and pathological conditions [39,40]. In
ing ANSYS CFX on 3D patient-specific models. The simulations were AF management and AF progression, the mitral flow velocity is an
performed for three cardiac cycles to reach periodicity. Each car- important feature [41,42]. Note that, in the current study, the si-
diac cycle was assumed 0.8 s or 75 beats per minute, and the cal- nus rhythm does not indicate normal LA contraction, and there
culations were run with 100 iterations per time step to ensure is only an association with mitral outflow profile. Sinus rhythm
solution convergence. The residuals for continuity and momen- (SR) and atrial fibrillation (AF) are related to the same boundary
tum equations were converged to in each time step. The blood in conditions were used by Bosi and Wang et al. to investigate LAA
LA/LAA was considered Newtonian, homogenous and incompress- shape effects [31,35]. Two mitral outflows help to evaluate affected
ible fluid with a density of ρ = 1060 kg/m^3 and a dynamic viscos- hemodynamic parameters due to shape differences under the same
ity of μ = 0.0035 kg/m-s. The non-Newtonian effect of the blood conditions. It worth mentioning, our study aims to investigate the
flow in the large cavity like the left atrium can be negligible. In LAA removal and LAA shape effects considering different geome-
these simulation models, the left atrium had four pulmonary veins tries, not to model LA function. So, we assume that LA function is
as inlets. The blood flow was also assumed as laminar. The gov- severely impaired, and the LA wall is rigid [31,32,35,36].
erning equations, including incompressible continuity and Navier-
Stokes equations, have been listed in Eq. 1 and Eq. 2. 3. Results

∇ · v = 0 (1) In this section, the hemodynamic characteristics of the blood


−  flow for each model are discussed. Besides, the consequences of

ρ vt + v · ∇v = −∇ P + μ∇ 2v (2) LAA removal in specific models are examined. The cardiac cycle
begins with the systolic phase when the mitral valve is closed. The
Where v is velocity vector, vt is velocity time derivative, P is pres- blood flow enters the left atrium chamber through the four pul-
sure, ρ is density, and μ dynamic viscosity. monary entrances. Then, the diastolic phase begins, and the mitral
valve opens, and blood flow passes through the mitral valve.
2.3. Boundary conditions As already mentioned, the conducted CFD simulation is for
three complete cardiac cycles for each model. After the second cy-
The opening boundary condition with zero constant pres- cle, the flow got fully periodic, and no considerable differences are
sure was considered for inlets (four pulmonary veins) [31]. At observed. All the reported results, hereafter, are from the third car-
the outlet (mitral valve), transient velocity profiles were used in diac cycle.
both sinus rhythm (SR) and atrial fibrillation (AF). By considering
each patient’s mitral orifice area and flow rate across the mitral 3.1. Hemodynamics characteristics in the left atrium
valve based on Gautam et al. s’ study, transmitral velocities were
achieved [31,35,38]. The transmitral flow curve has two waves, E- A box and whisker plots are used to compare the blood flow
wave and A-wave at the diastolic phase. E-wave corresponds to parameters in different geometries with defined mitral outflows.
the rapid filling of LV due to the pressure difference between the Like, Jia et al., used these plots to compare velocities in different

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L. Alinezhad, F. Ghalichi, M. Ahmadlouydarab et al. Computer Methods and Programs in Biomedicine 213 (2022) 106506

Fig. 2. The schematic of the geometry reconstruction from CT images: (a) LA mask in Mimics software, (b) Developed geometry volumes and surfaces, (c) quality of the
created meshes. Extended length of the inputs and output also have been shown.

locations inside the LA domain [32]. Generally, comparing the ve- Table 2
locity range between patients (with different conditions) reveals The range of velocity magnitudes for patient 1.
that in models with atrial fibrillation (models 3, 4, 7, and 8), the Model 1 Model 2 Model 3 Model 4
velocity magnitude reduces dramatically. In AF, the velocity drops Velocity (m. s−1 ) Velocity (m. s−1 ) Velocity (m. s−1 ) Velocity (m. s−1 )
inside the LA domain. Because, disappearing A-wave in AF effects Max: 0.185 Max: 0.188 Max: 0.183 Max: 0.187
the blood flow inside LA, in agreement with the literature [14]. Min: 0.0485 Min: 0.04603 Min: 0.0352 Min: 0.0367
The LAA morphology also impacts the magnitude of the velocity, in Q1: 0.06125 Q1: 0.0598 Q1: 0.0456 Q1: 0.0477
good agreement with the literature [43–45]. Figs. 4 and 5 show the Median: 0.089 Median: 0.0905 Median: 0.0634 Median: 0.0692
Q3: 0.133 Q3: 0.1350 Q3: 0.09405 Q3: 0.0994
average velocity distribution inside the left atrium for patient one
and patient two, respectively. Also, Tables 2 and 3 give information
about the interquartile range of velocity for both patients. Models Table 3
for patient two with one lobe appendage have considerable veloc- The range of velocity magnitude for patient 2.

ity differences, and the velocity increases under the same condi- Model 5 Model 6 Model 7 Model 8
tion (SR or AF), compared with two lobes appendage. For instance, Velocity (m. s−1 ) Velocity (m. s−1 ) Velocity (m. s−1 ) Velocity (m. s−1 )
in model 5 the maximum average velocity is 0.249 m/s (median Max: 0.249 Max: 0.243 Max: 0.241 Max: 0.2403
velocity 0.133 m/s, interquartile range: 0.09 to 0.17 m/s for one Min: 0.0675 Min: 0.0519 Min: 0.0486 Min: 0.03587
lobe appendage in sinus rhythm), but the highest velocity for pa- Q1: 0.0915 Q1: 0.0686 Q1: 0.06295 Q1: 0.0476
Median: 0.133 Median: 0.108 Median: 0.093 Median: 0.0713
tient 1 with two lobes is almost 0.19 m/s.
Q3: 0.178 Q3: 0.17 Q3: 0.134 Q3: 0.11

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L. Alinezhad, F. Ghalichi, M. Ahmadlouydarab et al. Computer Methods and Programs in Biomedicine 213 (2022) 106506

Fig. 3. The transmitral velocity profile. (a) Mitral flow velocity in sinus rhythm (SR), (b) Mitral flow velocity in atrial fibrillation (AF).

moving two lobes appendage (models 2 and 4) causes a slight in-


crease in blood flow velocity in both sinus rhythm (SR) and atrial
fibrillation (AF). By comparing models with LAA (models 1 and 3)
in Table 2, the median velocity in model 1(SR), from 0.089 m/s
(interquartile range: 0.0612 to 0.133 m/s) rises to 0.0905 m/s (in-
terquartile range: 0.0598 to 0.135 m/s) in model 2 (SR) with 1.7 %
increase. In models 3 and 4 (AF), median velocity increases by 9.15
% from 0.0634 m/s to 0.0692 m/s. However, models 5 and 6 (SR)
for patient 2 show 18.8% reduction in median velocity from 0.133
m/s to 0.17 m/s indicated in Table 3. Under AF condition, models 7
and 8, the median velocity decreases by 23.33% from 0.093 m/s to
0.0713 m/s.
The volume integral of vorticity shows the total reduction of
vorticity strength [32]. Figs. 6 and 7 show vorticity strength for
patients 1 and 2, respectively. In general, the magnitude of volume
integral vorticity drops under AF in the whole left atrial domain.
Fig. 4. The average velocity distribution inside left atrium for patient 1. Model 1:
Moreover, the LAA removal can affect the vorticity magnitude in
Appendage with two lobes in sinus rhythm (SR), Model 2: Removed two lobes ap- the left atrial domain in two opposite directions.
pendage in SR, Model 3: Appendage with two lobes in atrial fibrillation (AF), Model Fig. 6 and Table 4 show the interquartile range and the me-
4: Removed two lobes appendage in AF. dian value of vorticity for patient 1. Under SR condition, mod-
els 1 and 2, the vorticity strength decreases 1.1% by removing
LAA. On the other hand, models 3 and 4 have a slight increase
Furthermore, simulation results demonstrate that the LAA re- in vorticity magnitude (by 7.27% rise shown in Table 4). Results
moval affects velocity magnitude for models 2, 4, 6, and 8. Re- for patient two shown in Fig. 7 and Table 5 depict a reduction

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L. Alinezhad, F. Ghalichi, M. Ahmadlouydarab et al. Computer Methods and Programs in Biomedicine 213 (2022) 106506

Table. 4
The range of volume integral vorticity for patient 1.

Model 1 Model 2 Model 3 Model 4


Volume integral of vorticity (m3 .s−1 ) Volume integral of vorticity (m3 .s−1 ) Volume integral of vorticity (m3 .s−1 ) Volume integral of vorticity (m3 .s−1 )

Max: 7.57 × 10−3 Max: 7.42 × 10−3 Max: 7.19 × 10−3 Max: 7.14 × 10−3
Min: 2.97 × 10−3 Min: 2.81 × 10−3 Min: 2.22 × 10−3 Min: 2.21 × 10−3
Q1: 3.765 × 10−3 Q1: 3.85 × 10−3 Q1: 2.81 × 10−3 Q1: 2.9 × 10−3
Median: 5.61 × 10−3 Median: 5.55 × 10−3 Median: 3.85 × 10−3 Median: 4.13 × 10−3
Q3: 6.47 × 10−3 Q3: 6.38 × 10−3 Q3: 5.37 × 10−3 Q3: 5.48 × 10−3

Table .5
The range of volume integral vorticity for patient 1.

Model 5 Model 6 Model 7 Model 8


Volume integral of vorticity (m3 .s−1 ) Volume integral of vorticity (m3 .s−1 ) Volume integral of vorticity (m3 .s−1 ) Volume integral of vorticity (m3 .s−1 )

Max: 7.98 × 10−3 Max: 7.039 × 10−3 Max: 7.448 × 10−3 Max: 6.772 × 10−3
Min: 3.12 × 10−3 Min: 2.30 × 10−3 Min: 2.131 × 10−3 Min: 1.619 × 10−3
Q1: 4.085 × 10−3 Q1: 3.18 × 10−3 Q1: 2.84 × 10−3 Q1: 2.20 × 10−3
Median: 5.6 × 10−3 Median: 4.86 × 10−3 Median: 3.98 × 10−3 Median: 3.249 × 10−3
Q3: 6.59 × 10−3 Q3: 5.78 × 10−3 Q3: 5.54 × 10−3 Q3: 4.851 × 10−3

Fig. 5. The average velocity distribution inside the left atrium domain for patient Fig. 7. The volume integral of vorticity distribution for patient 1.
2. Model 5: Appendage with one lobe in sinus rhythm (SR), Model 6: Removed ap-
pendage in SR, Model 7: Appendage with one lobe in atrial fibrillation (AF), Model
8: Removed appendage in AF.
3.2. The left atrial appendage flow characteristics

The velocity along the LAA, at the ostium, and the vorticity in-
side LAA are the main parameters to describe LAA hemodynam-
ics [2,31,33,34]. Fig. 8 and Fig. 10 shows the blood flow magnitude
and direction at the LAA ostium for patient one and two, respec-
tively. At the beginning of the diastolic phase (40% tc ), the velocity
magnitude is considerably low for patient one (Fig. 8) compared
to patient two (Fig. 9). At 55% tc (Peak E), The blood flow veloc-
ity increases in both patients, and the blood enters the LAA cav-
ity. Then, at 75% tc , the velocity magnitude drops and the blood
is emptying from the LAA. However, the differences in velocities
become noticeable at 100%. The low-velocity magnitude at ostium
can be observed in models with AF, associating with increasing the
possibility of thrombus. Fig. 9 (a) shows the velocity magnitude at
LAA ostium for patient one. At the beginning of the cardiac cy-
cle, the velocity is low in the AF condition (model 3), but at 55%
tc , the velocity precedes the SR condition. However, at the end of
the cardiac cycle, the blood flow velocity drops considerably in AF
Fig. 6. The Volume integral of vorticity distribution for patient 1. (model 3). The velocity magnitude increases at the end of the car-
diac cycle, comparing to model 1. In Fig. 10, The velocity vectors for
patient two have a similar trend like the patient one, but the ve-
in vorticity under LAA removal conditions, i.e., 13.2% and 18.36% locity magnitudes changes. Comparing the velocity magnitudes in
for models 6 and 8, respectively. Our results for patient 2 with Fig. 9 and Fig. 11 shows that the one lobe appendage has a higher
one lobe appendage are comparable with reported data by Jia average velocity at LAA ostium. However, the average area velocity
et al [32]. magnitude drops for two lobes appendage. Consequently, the pos-

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L. Alinezhad, F. Ghalichi, M. Ahmadlouydarab et al. Computer Methods and Programs in Biomedicine 213 (2022) 106506

Fig. 8. The velocity vectors at the LAA ostium (Patient one; Model 1 and Model 3).

Fig. 9. The velocity magnitude profile patient one (Model 1 and 3). (a) The velocity profile at the LAA ostium plane. (b) The velocity profile inside LAA along the AB line.

sibility of the thrombogenicity increases in two lobes appendage and model 7 is higher than that of model 3. Also, by comparing
[2,45]. the velocity profiles in Fig. 9 (a and b) and Fig. 11 (a and b), it is
The velocity profiles at the end of the cardiac cycle have been concluded that LAA shape differences may affect the velocity pro-
presented in Fig. 9(b) and Fig. 11 (b). In SR, the blood flow veloc- file. As shown in Fig .9 (b) and Fig. 11 (b), the velocity magnitude
ity in the left atrial appendage drops along the AB line steadily drops considerably at the tip of LAA in both patients. So, the dis-
for models 1 and 5. Note that velocity reduction inside the LAA is tal part of LAA is the possible region for having thrombus due to
more dominant for models 3 and 7, under AF. Furthermore, com- almost zero blood flow velocity [31,32,35,43].
paring velocity profiles in Fig .9 (b) and Fig. 11 (b) together reveals Fig. 12 shows the vorticity magnitude within the left atrial ap-
that the velocity value for model 5 is higher than that of model 1, pendage. In general, atrial fibrillation increases the strength of vor-

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L. Alinezhad, F. Ghalichi, M. Ahmadlouydarab et al. Computer Methods and Programs in Biomedicine 213 (2022) 106506

Fig 10. The velocity vectors and contours at the LAA ostium plane (Patient two; Model 5 and 7).

Table 6
The rang of volume integral vorticity inside LAA for models.

Model 1 Model 3 Model 5 Model 7


Volume integral of vorticity (m3 .s−1 ) Volume integral of vorticity (m3 .s−1 ) Volume integral of vorticity (m3 .s−1 ) Volume integral of vorticity (m3 .s−1 )

Max: 6.28 × 10−5 Max: 9.10 × 10−5 Max: 3.02 × 10−5 Max: 5.69 × 10−5
Min: 3.74 × 10−5 Min: 2.44 × 10−5 Min: 1.46 × 10−5 Min: 2.99 × 10−5
Q1: 4.27 × 10−5 Q1: 3.13 × 10−5 Q1: 1.78 × 10−5 Q1: 4.09 × 10−5
Median: 4.57 × 10−5 Median: 4.52 × 10−5 Median: 2.19 × 10−5 Median: 4.44 × 10−5
Q3: 5.46 × 10−5 Q3: 6.68 × 10−5 Q3: 2.63 × 10−5 Q3: 4.65 × 10−5

ticity inside the LAA domain. Especially Model 3 has a wide vortic- stroke [46,47]. It is also possible to correlate LAA morphology with
ity range and magnitude. The median value is almost the same in platelet activity, fibrinolysis function, endothelial dysfunction, and
models 1 and 3, but the interquartile range increases by 78.4% in inflammation [48]. Consequently, the study of LAA morphology can
model 3. Besides, by comparing models 5 and 7 together, a consid- stratify the risk for thrombosis and stroke in AF patients. Accord-
erable rise in AF condition can be observed in both median values ing to the statistical analysis, the shapes of LAA lead to different
and interquartile ranges according to Table 6. stroke risk rates in patients with AF. Several studies show LAA ori-
fice area, LAA depth, LAA volume, and LAA flow velocity impact
4. Discussion thrombotic events. A larger LAA orifice size or an increased LAA
volume, along with a decreased LAA velocity, are strongly associ-
This numerical study explored LAA’s shape effects on hemo- ated with higher stroke risk in AF [44,49-53].
dynamic properties in two cases. Furthermore, this work investi- It is evident that under AF, the velocity and vorticity decreased
gated whether LAA removal can reduce thrombosis. Patient 1 had a inside the LA domain. Due to the absence of A- wave in AF, the
two-lobe appendage, and patient 2 had one lobe. The results illus- blood flow in the LA domain cannot wash out properly from the
trated that AF and LAA morphology had significant roles in throm- domain at the end of the diastolic phase. Besides, velocity dropped
bus formation. Anatomical, morphological, and hemodynamic ab- considerably inside LAA associated with increasing the thrombo-
normalities happen in LAA under AF conditions. In patients with genicity in this region [31–35]. The LAA tip had the lowest velocity
AF, increased blood stasis, endothelial dysfunction or damage, and value in both patients, and the blood flow is almost zero [32–36].
atrial tissue injury caused thrombus formation and subsequent Furthermore, the well-known factors to estimate thromboses in-

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L. Alinezhad, F. Ghalichi, M. Ahmadlouydarab et al. Computer Methods and Programs in Biomedicine 213 (2022) 106506

Fig. 11. The velocity magnitude profile patient one (Model 1 and 3). (a) The velocity profile at the LAA ostium plane. (b) The velocity profile inside LAA along the AB line.

morphology of the LAA can influence blood flow parameters, even


after the LAA removal. For this purpose, two patients with different
shapes and volumes of LAA were considered.
Also, in this research, the sinus rhythm was not associated with
normal LA contraction, and this assumption was for investigating
the mitral outflow impacts. The LA wall was rigid, with severely
impaired LA function. Based on the LA impairment, the wall mo-
tion could be reduced [55]. So, only the LAA morphology and its
effects on the blood flow were investigated. However, considering
left atrial wall motion with immersed-boundary CFD analyses of
LA blood flow is essential in future studies to reach patient-specific
data for predicting LAA thrombosis.
Our results with other literature data indicated that LAA mor-
phology parameters (volume, lobe, and complexity) affected hemo-
Fig. 12. The volume integral vorticity inside the LAA. dynamics inside the LA and LAA [30,31,37,43]. Otani et al. showed
that the relatively simple LAA morphology with low kinetic energy
was less related to stroke risk than a more complex LAA morphol-
ogy with high kinetic energy [30]. Other than LA wall motion, LAA
side LAA are lobes number [54]. Thrombosis risk is relatively high morphology can play a critical role in blood flow and thrombo-
in LAA with two lobes and large volume due to the wide vorticity sis [30,37]. Also, there are clinical studies that support our results
range or/and low-velocity values [2,30,45]. [49–55].
In the case of LAA removal in patient 1 (two-lobe appendage),
there was no significant change in velocity and vorticity under 5. Conclusion
SR. While, the magnitudes were slightly high under AF, 9.15% and
7.27% rise in velocity and vorticity, respectively. The changes in This study confirmed that a relatively complex LAA geometry
blood flow velocity and vorticity in patient 2 (one-lobe appendage) could affect the hemodynamics in the domain and increase the
were more dominant than the other one. The velocity and vorticity thrombus formation. LAA with two lobes and higher volume was
decreased due to LAA removal under SR (18.8 % and 13.2%, respec- more likely to have a thrombosis. The number of lobes influenced
tively) and AF (23.33% and 18.6%, respectively). Under the same fluid dynamics. Also, in the same condition, morphological differ-
conditions, LAA morphology may influence LAA removal impacts ences can affect LAA removal consequences. Despite the limitation
and cause unexpected results depending on the morphology. In in the LA movement and subject number, the current study cov-
one lobe appendage, the LAA removal effects were more dominant, ered fluid dynamic simulation evaluating LAA removal effective-
especially under AF, resulting in unforeseen consequences. The LAA ness in patient-specific geometries, under different simulation con-
morphological characteristics make it hard to estimate LAA isola- ditions.
tion impacts in patients with persistent AF.
This study had both strengths and limitations by considering Conflict of Interest
two patients. It is necessary to consider more patients to deter-
mine whether the results are reliable and applicable clinically. It is None
recommended for future studies to include patients with paroxys-
mal AF, patients with persisting AF, and patients without AF. Fur- Acknowledgements
thermore, since LAA has a wide range of shapes, more computa-
tional studies are needed to understand the shape impacts in dif- The authors would like to greatly thank Rajaie Cardiovascular,
ferent subjects. In the current study, it aimed to show that the Medical, and Research Center for providing CT images.

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L. Alinezhad, F. Ghalichi, M. Ahmadlouydarab et al. Computer Methods and Programs in Biomedicine 213 (2022) 106506

References [30] T. Otani, et al., A computational framework for personalized blood flow analy-
sis in the human left atrium, Ann. Biomed. Eng. 44 (11) (2016) 3284–3294.
[1] N. Al-Saady, O. Obel, A. Camm, Left atrial appendage: structure, function, and [31] G.M. Bosi, et al., Computational fluid dynamic analysis of the left atrial ap-
role in thromboembolism, Heart 82 (5) (1999) 547–554. pendage to predict thrombosis risk, Front. Cardiovascular Med. 5 (2018) 34.
[2] R. Beigel, et al., The left atrial appendage: anatomy, function, and noninvasive [32] D. Jia, et al., Image-based flow simulations of pre-and post-left atrial ap-
evaluation, JACC: Cardiovascular Imaging 7 (12) (2014) 1251–1265. pendage closure in the left atrium, Cardiovascular Eng. Technol. 10 (2) (2019)
[3] L. Di Biase, et al., Does the left atrial appendage morphology correlate with 225–241.
the risk of stroke in patients with atrial fibrillation? Results from a multicenter [33] A. Masci, et al., A proof of concept for computational fluid dynamic analysis of
study, J. Am. Coll. Cardiol. 60 (6) (2012) 531–538. the left atrium in atrial fibrillation on a patient-specific basis, J. Biomech. Eng.
[4] F. Lupercio, et al., Left atrial appendage morphology assessment for risk strat- 142 (1) (2020).
ification of embolic stroke in patients with atrial fibrillation: a meta-analysis, [34] A. Masci, et al., The impact of left atrium appendage morphology on stroke risk
Heart Rhythm 13 (7) (2016) 1402–1409. assessment in atrial fibrillation: a computational fluid dynamics study, Front.
[5] N. Özer, et al., Left atrial appendage function in patients with cardioembolic Physiology 9 (2019) 1938.
stroke in sinus rhythm and atrial fibrillation, J. Am. Soc. Echocardiogr. 13 (7) [35] Y. Wang, et al., Numerical prediction of thrombosis risk in left atrium un-
(20 0 0) 661–665. der atrial fibrillation, Mathematical Biosciences and Engineering 17 (3) (2020)
[6] E.J. Benjamin, et al., Impact of atrial fibrillation on the risk of death: the Fram- 2348–2360.
ingham Heart Study, Circulation 98 (10) (1998) 946–952. [36] B.M. Fanni, et al., Correlation between LAA morphological features and com-
[7] H. Vidaillet, et al., A population-based study of mortality among patients with putational fluid dynamics analysis for non-valvular atrial fibrillation patients,
atrial fibrillation or flutter, Am. J. Med. 113 (5) (2002) 365–370. Applied Sciences 10 (4) (2020) 1448.
[8] V. Widgren, et al., Aortic stenosis and mitral regurgitation as predictors of [37] M. García-Villalba, et al., Demonstration of Patient-specific simulations to as-
atrial fibrillation during 11 years of follow-up, BMC cardiovascular disorders sess left atrial appendage thrombogenesis risk, Front. Physiol. 12 (2021).
12 (1) (2012) 1–8. [38] S. Gautam, R.M. John, Interatrial electrical dissociation after catheter-based ab-
[9] B. Iung, A. Leenhardt, F. Extramiana, Management of atrial fibrillation in pa- lation for atrial fibrillation and flutter, Circulation 4 (4) (2011) e26–e28.
tients with rheumatic mitral stenosis, Heart 104 (13) (2018) 1062–1068. [39] J. Caudron, et al., Evaluation of left ventricular diastolic function with cardiac
[10] N.F. Marrouche, et al., Association of atrial tissue fibrosis identified by delayed MR imaging, Radiographics 31 (1) (2011) 239–259.
enhancement MRI and atrial fibrillation catheter ablation: the DECAAF study, [40] L.T. Zhang, M. Gay, Characterizing left atrial appendage functions in sinus
JAMA 311 (5) (2014) 498–506. rhythm and atrial fibrillation using computational models, J. Biomech. 41 (11)
[11] M.S. Dzeshka, et al., Cardiac fibrosis in patients with atrial fibrillation: mecha- (2008) 2515–2523.
nisms and clinical implications, J. Am. Coll. Cardiol. 66 (8) (2015) 943–959. [41] L.K. Williams, et al., Effect of left ventricular outflow tract obstruction on
[12] Y. Seko, et al., Association between atrial fibrillation, atrial enlargement, and left atrial mechanics in hypertrophic cardiomyopathy, Biomed. Res. Int. (2015)
left ventricular geometric remodeling, Sci. Rep. 8 (1) (2018) 1–8. 2015.
[13] N. Naksuk, et al., Left atrial appendage: embryology, anatomy, physiology, ar- [42] T. Nakagawa, et al., Transmitral inflow wave and progression from paroxysmal
rhythmia and therapeutic intervention, JACC: Clin. Electrophysiol. 2 (4) (2016) to permanent atrial fibrillation in Asian people, Heart Asia 11 (2) (2019).
403–412. [43] G. García-Isla, et al., Sensitivity analysis of geometrical parameters to study
[14] T. Kojima, et al., Left atrial global and regional function in patients with haemodynamics and thrombus formation in the left atrial appendage, Interna-
paroxysmal atrial fibrillation has already been impaired before enlargement tional journal for numerical methods in biomedical engineering 34 (8) (2018)
of left atrium: velocity vector imaging echocardiography study, Eur. Heart e3100.
J.–Cardiovascular Imaging, 13 (3) (2012) 227–234. [44] J.M. Lee, et al., Additional value of left atrial appendage geometry and hemody-
[15] R. Mahajan, et al., Importance of the underlying substrate in determining namics when considering anticoagulation strategy in patients with atrial fibril-
thrombus location in atrial fibrillation: implications for left atrial appendage lation with low CHA2DS2-VASc scores, Heart Rhythm 14 (9) (2017) 1297–1301.
closure, Heart 98 (15) (2012) 1120–1126. [45] S. Yaghi, et al., Left atrial enlargement and stroke recurrence: the Northern
[16] A.S. Kanderian, et al., Success of surgical left atrial appendage closure: assess- Manhattan Stroke Study, Stroke, 46 (6) (2015) 1488–1493.
ment by transesophageal echocardiography, J. Am. Coll. Cardiol. 52 (11) (2008) [46] T. Watson, E. Shantsila, G.Y. Lip, Mechanisms of thrombogenesis in atrial fib-
924–929. rillation: Virchow’s triad revisited, Lancet North Am. Ed. 373 (9658) (2009)
[17] S. Mohanty, et al., Risk of thromboembolic events after percutaneous left atrial 155–166.
appendage ligation in patients with atrial fibrillation: Long-term results of a [47] A.R. Anan, et al., Left atrial appendage morphology as a determinant for stroke
multicenter study, Heart Rhythm 17 (2) (2020) 175–181. risk assessment in atrial fibrillation patients: systematic review and meta–
[18] A. Aryana, et al., Association between incomplete surgical ligation of left atrial analysis, J. Atrial Fibrillation 12 (2) (2019).
appendage and stroke and systemic embolization, Heart Rhythm 12 (7) (2015) [48] B. Xu, et al., Left Atrial Appendage Morphology and Local Thrombogenesis-Re-
1431–1437. lated Blood Parameters in Patients With Atrial Fibrillation, J. Am. Heart Assoc.
[19] R. Koizumi, et al., Numerical analysis of hemodynamic changes in the left 10 (2021) e020406.
atrium due to atrial fibrillation, J. Biomech. 48 (3) (2015) 472–478. [49] L.D. Burrell, et al., Usefulness of left atrial appendage volume as a predictor of
[20] A. Fyrenius, et al., Three dimensional flow in the human left atrium, Heart 86 embolic stroke in patients with atrial fibrillation, Am. J. Cardiol. 112 (8) (2013)
(4) (2001) 448–455. 1148–1152.
[21] M.A. García-Fernández, et al., Left atrial appendage Doppler flow patterns: im- [50] I.M. Khurram, et al., Relationship between left atrial appendage morphology
plications on thrombus formation, Am. Heart J. 124 (4) (1992) 955–961. and stroke in patients with atrial fibrillation, Heart rhythm 10 (12) (2013)
[22] M. Bansal, R.R. Kasliwal, Echocardiography for left atrial appendage structure 1843–1849.
and function, Indian Heart J. 64 (5) (2012) 469. [51] S.A. Sakr, et al., Association between left atrial appendage morphology eval-
[23] M. Markl, et al., Left atrial and left atrial appendage 4D blood flow dynamics uated by trans-esophageal echocardiography and ischemic cerebral stroke in
in atrial fibrillation, Circulation 9 (9) (2016) e004984. patients with atrial fibrillation, Int. Heart J. 56 (3) (2015) 329–334.
[24] S.N. Doost, et al., Heart blood flow simulation: a perspective review, Biomed. [52] J.M. Lee, et al., Why is left atrial appendage morphology related to strokes?
Eng. Online 15 (1) (2016) 1–28. An analysis of the flow velocity and orifice size of the left atrial appendage, J.
[25] J. Heijman, et al., Translational challenges in atrial fibrillation, Circ. Res. 122 (5) Cardiovasc. Electrophysiol. 26 (9) (2015) 922–927.
(2018) 752–773. [53] K. Fukushima, et al., Correlation between left atrial appendage morphology
[26] E. Grandi, D. Dobrev, J. Heijman, Computational modeling: What does it tell us and flow velocity in patients with paroxysmal atrial fibrillation, Eur. Heart
about atrial fibrillation therapy? Int. J. Cardiol. 287 (2019) 155–161. J.-Cardiovascular Imaging 17 (1) (2016) 59–66.
[27] K.N. Aronis, R. Ali, N.A. Trayanova, The role of personalized atrial modeling in [54] M. Yamamoto, et al., Complex left atrial appendage morphology and left atrial
understanding atrial fibrillation mechanisms and improving treatment, Int. J. appendage thrombus formation in patients with atrial fibrillation, Circulation:
Cardiol. 287 (2019) 139–147. Cardiovascular Imaging 7 (2) (2014) 337–343.
[28] C.M. Augustin, et al., The impact of wall thickness and curvature on wall [55] B.D. Hoit, Left atrial size and function: role in prognosis, J. Am. Coll. Cardiol.
stress in patient-specific electromechanical models of the left atrium, Biomech. 63 (6) (2014) 493–505.
Model. Mechanobiol. 19 (3) (2020) 1015–1034.
[29] R. Mittal, et al., Computational modeling of cardiac hemodynamics: current
status and future outlook, J. Comput. Phys. 305 (2016) 1065–1082.

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