Medicine in Novel Technology and Devices 16 (2022) 100135

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Medicine in Novel Technology and Devices

journal homepage: www.journals.elsevier.com/medicine-in-novel-technology-and-devices/

Full Length Article

A new way to evaluate thrombotic risk in failure heart and ventricular

assist devices
Yuan Li, Yifeng Xi, Hongyu Wang, Anqiang Sun, Xiaoyan Deng, Zengsheng Chen *, Yubo Fan **
Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School
of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, China

A R T I C L E I N F O A B S T R A C T

Keywords: Thrombosis is one of the main complications in patients implanted with ventricular assist device (VAD). The
Ventricular assist device complicated structure and disturbed flow field within failure heart and blood pump play an important role in
Left ventricle size thrombosis formation. In this study, the influence of Left ventricular (LV) volumes on flow field contributing to
Thrombogenic potential
thrombosis formation within failure heart and VAD was investigated. Computational Fluid Dynamics (CFD)
Non-physiological shear stress
Residence time
methods were employed to investigate the effect of different LV volumes on the thrombogenic potential of failure
heart and VAD. Lagrangian methods were utilized to obtain information on platelet voyage trajectories. The
concepts of mean and threshold of stress accumulation and residence time were introduced to accurately assess
the likelihood of thrombus. Eulerian methods were used to identify thrombus-prone locations. CFD results showed
that residence time (RT) was the main cause of thrombus formation in the failure heart, and the percentage of
platelet trajectories above the RT threshold increased significantly with increasing LV volume. The RT in the left
atrial appendage and LV increased significantly with LV volume increasing, which indicated that thrombus is
prone to form there. Compared with the failure heart, non-physiological shear stress (NPSS)-caused platelet
activation is the main reason for thrombus formation within VAD. The narrow zones (top clearance and secondary
flow passage) within VAD have a high incidence of thrombus generation. In VAD patients, the LV volume has an
important impact on thrombosis probability within failure heart, in which the larger size of the LV volume is, the
higher risk of thrombosis will be. The size of LV volume has little effect on the thrombosis formation probability of
VAD, where the NPSS plays the leading role in thrombosis formation. The finding of this study can be utilized to
guild the clinical treatment and VAD structure optimization design for reducing the thrombosis risk.

1. Introduction
Heart failure (HF) is a growing healthcare problem with high
morbidity and mortality. Despite medical advances and surgical treat-
ment, more than 40% of patients diagnosed with HF will die within 5
years [1,2]. For patients with advanced HF (stage D heart failure), heart
transplantation is the best treatment option [3], but the stringent patient
requirements and the limited number of donor hearts (approximately
5500 in 2020 [4]) cannot meet the growing demand [5]. To address this
unmet clinical need, mechanical circulatory support (MCS) devices have
been proposed and developed over time. Early pulsatile devices used
displacement pumps to mimic the function of the heart, but they were
bulky and had limited durability and lifespan [6]. In the last decade,
significant progress has been made with the development of small,
durable ventricular assist devices (VAD), which is a rotary blood pump.
VAD has evolved into the standard of care for advanced HF, with a
one-year survival rate of approximately 90% [1,2,7], approaching those
of heart transplant recipients [8]. However, currently available VAD
therapy remains suboptimal and is often associated with serious com-
plications, including thrombosis-induced stroke and thrombus formation
within the VAD which can cause device dysfunction. Therefore, there is a
great need for finding quantitative methods to assess the risk factors
affecting thrombosis in VAD therapy [1,7,9–11].
Thrombus formation is profoundly influenced by local surrounding
hemodynamics. Platelets which play an important role in thrombosis and
hemostasis, can sense their microenvironment and initiate coagulation
cascades under specific mechanical and chemical conditions [12]. The
structure of VAD and failure heart including left ventricular (LV), left

* Corresponding author.
** Corresponding author.
E-mail addresses: czsbme@buaa.edu.cn (Z. Chen), yubofan@buaa.edu.cn (Y. Fan).

https://doi.org/10.1016/j.medntd.2022.100135
Received 20 February 2022; Received in revised form 13 April 2022; Accepted 18 April 2022
2590-0935/© 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
Y. Li et al.
atrium (LA) and left atrial appendage (LAA) are complicated, which all
include disturbed zones. When platelets move through the failure heart
and VAD, the chaotic hemodynamic characteristics, such as blood stag-
nation and high shear stress, can affect platelets, leading to platelet
activation, aggregation and adhesion and even causing thrombosis for-
mation or cerebrovascular stroke events [12,13]. Studies have shown
that low-level shear stress (<0.35 Pa) with a long residence time [14] can
lead to the release of small amounts of ATP, ADP, and 5-hydroxytrypta-
mine and further cause platelet aggregation [15,16]. The pathological
high-level shear stress level of 31.5 Pa encountered in arteries with se-
vere atherosclerosis can also activate platelets and trigger platelet
microparticle production. When levels of the non-physiological shear
stress (NPSS) exceed 100Pa, platelets can become activated even with
very a short exposure time (<1s) [17–20]. Previous studies had investi-
gated the effects of the intra-left atrium (LA) hemodynamic parameters
on platelets under VAD treatment strategies, ignoring platelet activation
within left ventricular (LV) and VAD, and also the mutual interference
among LA, LV, and VAD [20–22]. For the interaction between VAD and
failure heart, the blood flow within failure heart is inherently unstable
due to the high Reynolds number and complex geometry [23].
Previous assessments of thrombus related hemodynamic metrics have
tended to focus on Eulerian methods, such as wall shear stress [24],
which are more applicable to understanding the endothelial cell response
rather than the activation, transport, and aggregation of platelets sus-
pended in the blood. Therefore, to quantify the complex hemodynamic
and thrombogenic potential in cardiovascular devices, Bluestein et al.
proposed a Lagrangian-based method to quantitatively examine the role
of stress accumulation (SA) on platelet activation [25–27], which was
shown to be in good agreement with experiments [13,25,28,29]. Based
on the same method, Aliseda et al. introduced the concept of residence
time (RT) along circulating platelet trajectories, and quantified SA and
RT to assess the influences of shear stress and RT on platelet activation
using median and outliers [20,22,30]. The platelet trajectories informa-
tion (SA and RT) is sorted from largest to smallest, and the information of
platelet trajectories at the 50% position is the median value. The outliers
are values greater than the max value and less than the min value. The
min and max value is obtained by the following formula [20,22,30]:
Min ¼ Q̄̄ 1:5ðQ3  Q1 Þ
Max ¼ Q3 þ 1:5ðQ3  Q1 Þ
where, Q1 and Q3 are the information of platelet trajectories at 25% and
75% positions, respectively. This method of obtaining outliers makes the
starting values (Min and Max) vary greatly in different models. There-
fore, it lacks the quantitative analysis to compare the thrombotic po-
tential of different models. Meanwhile, in that mothed, the information
on platelet trajectories that is smaller than the min value (such as low SA
and short RT) also be considered as an important part of outliers. How-
ever, the low SA and short RT have a low impact on thrombus formation.
The concept of threshold is employed in many Eulerian models of
thrombosis and it is believed that the effect of non-physiological shear
stress factors on platelets is small when these factors are below the
threshold [14,31,32]. Based on the above, we introduced the concept of
mean and threshold value to better assess the effect of SA and RT on
thrombosis.
In the paper, the influence of different size LV volumes on the flow
field contributing to the thrombosis formation within the failure heart
and VAD was investigated. The combined effect of LA, LAA, LV and
connected VAD on hemodynamic performance, and the main contribu-
tors for thrombosis formation in failure heart and VAD were analyzed.
Lagrangian particle trajectory metrics were quantified based on mean
and threshold values to compare the influence of LV size on the throm-
botic performance of failure heart and VAD. Eulerian methods were used
to identify thrombus-prone locations.
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Medicine in Novel Technology and Devices 16 (2022) 100135
2. Materials and methods
2.1. Studied models
This study was approved by the Institutional Review Board at the
School of Biological Science and Medical Engineering at Beihang Uni-
versity. The commercial software Mimics (Materialise Inc., Belgium) was
employed to reconstruct a 3D heart failure model from CT data. In a first
step, a rough mask of the LV, LA and LAA was formed by selecting the
region of interest within the failure heart. A 3D STL file was then created
and exported to Geomagic Studio (Geomagic Inc., Triangle Development
District, NC, USA), where filtering procedures such as smoothing and
removal of spikes were applied. The LV diameter was measured at 6 cm
and the volume was 93.5 cm3, named as HF0 model. While keeping the
LA geometry and volume unchanged, a thickening operation was
employed to obtain LV models with volumes of 178 cm3 (HF1 model) and
326 cm3 (HF2 model), respectively, according to the model building
method of Aigner et al. [24], as shown in Fig. 1. These models of HF0,
HF1 and HF2 represent the different degrees of HF conditions. All the
above models were confirmed by radiologists to ensure the validity of the
models.
The geometry of VAD used in this study is the CH-VAD (CH
Biomedical, Inc., Suzhou, China), as shown in Fig. 2a and b, which is a
fully maglev continuous flow-Left VAD. It consists of a rotor and casing,
while a secondary flow passage is provided to avoid flow stagnation. The
whole size of CH-VAD is small, which has demonstrated superiority in
hemocompatibility [5,33]. The connection between VAD and LV apical is
performed in a standard surgical fashion, consistent with contemporary
clinical practice, as shown in Fig. 2c.
2.2. CFD methods
The blood moves in the failure heart and VAD is set to be a three-
dimensional, incompressible Newtonian fluid20-22 with a density of
1055 kg/m3 and a viscosity of 0.0035 Pa s [34]. For the VAD, the rotating
regions (impeller, cavity and secondary flow passage) and the stagnant
regions (inlet pipe and volute) are combined by the frozen rotor interface
[35–37]. The Reynolds-Averaged Navier-Stokes (RANS) equations were
solved using the commercial software ANSYS CFX (ANSYS Inc., Can-
onsburg, PA, USA), which employs a finite-volume method based on
discretization of the governing equations. The convective terms were
solved in high-resolution form and the SST k-ω turbulence model was
employed for steady simulations [34,37]. In the case of complete heart
failure, the aortic valve is considered to be completely closed, therefore,
the wall boundary condition is employed. The four Pulmonary Veins
(PVs) were set as inlets and were extended to avoid the influence of flow
disturbance in the inlet. Based on clinical measurements, the inlet
boundary was the total pressure, 5 mmHg, and the pump outlet was set as
the outlet of the entire fluid domain, the outlet boundary condition was
set to a mass flow rate of 0.079 kg/s (obtained from a volume flow rate of
4.5 L/min) and the convergence criterion was set to 106.
The voyage of platelet-surrogate particles was simulated in order to
obtain information about the platelet microenvironment. The diameter of
particles was set to be 3 μm [38] and the number of 4000 particles was
released at each PA inlet. A total of 16,000 particles [20,22,30,39] were
used in this study. The trajectories of platelets within the LA, LAA, LV and
VAD routes were mapped by calculating the balance between inertia and
drag of the particles in the Lagrangian reference system. The platelets
were allowed to collide elastically with walls through a collision model in
order to retain them within the fluid domain.
2.3. Euler scalar shear stress predictions
The viscous scalar shear stress (SSS) was derived from the simulated
flow fields to represent non-physiological shear stress (NPSS) according
to the following formula [40]:
Y. Li et al. Medicine in Novel Technology and Devices 16 (2022) 100135

Fig. 1. 3D model of the studied failure heart with different left ventricular sizes: (a) HF0 (the volume of LV is 93.5 cm3) (b) HF1 (the volume of LV is 178 cm3) and (c)
HF2 (the volume of LV is 326 cm3).

Fig. 2. 3D model of VAD and connection method: (a) Appearance of the studied VAD (b) Cross-section of the studied VAD and (c) Connection of failure heart
and VAD.

X 1
2 X 
=
1   2 thrombosis [42,43]. The Eulerian RT obeys the following equation [14]:
σ¼ σ ii  σ jj þ σ ij σ ij
6
∂RT
þ v  rRT ¼ DRT r2 RT þ 1
∂t
where σ is the shear stress tensor, which is calculated by multiplying the
shear rate tensor σ ij ¼ ∂σ i =∂σ j , with the blood viscosity. where t is time, v is the velocity of blood, DRT represents the self-
diffusivity of blood (DRT ¼ 1.14  1011 m2/s [14]) and the source is
2.4. Lagrangian stress accumulation predictions consistent with the variation of time.
The Lagrangian RT is obtained by particle trajectories [30]:
Stress accumulation (SA) is the integral of stress over time, which is a
record of the shear stresses experienced by platelet particles within the RTi ¼ Tioutlet  Tiinlet
LA, LAA, LV and VAD system along the corresponding trajectory. It can be
numerically approximated as the sum of the instantaneous stress where i is the number of each particle, Tiinlet represents the time when the
magnitude and the product of the exposure time [41]: particle i moved into the fluid domain, and Tioutlet represents the time
when the particle i moved out of the fluid domain.
Zt exp X
N
σ i þ σ iþ1
SA ¼ σ ðtÞdt   Δt 2.6. Lagrangian thrombogenic potential predictions
i¼1
2
t0

This study develops the thrombogenic potential (TP) model based on

where σi, i ¼ 1~N, is the nodal scalar value extracted from the scalar
shear stress described above, Δt is the exposure time which is the cor-
responding time step between consecutive nodes at platelet trajectories,
and the resulting SA units are in Pa⋅s.
2.5. Euler & Lagrangian residence time predictions
Residence time (RT) is employed to determine the areas of stagnation
and flow re-circulation. The deposition of blood components (platelets,
fibrinogen, etc.) in the areas with long RT can lead to the formation of
the work of Aliseda et al. [20–22,24] to assess the probability of
thrombosis generation using the information of the mean and percentage
above threshold values [22] of SA and RT obtained from platelet tra-
jectories. Specifically, the RT and SA distributions of platelets were
normalized and weighted statistically to obtain TP as shown in Table 1.
2.7. Grid sensitivity analysis and verification
ANSYS ICEM (ANSYS Inc., Canonsburg, PA, USA) was employed to
generate a hybrid grid including a 5-element boundary layer along the

3
Y. Li et al.
Table 1
The evaluation method of TP.
Normalization RT SA
Mean percentage of RT Mean percentage of
RT  5s [%] SA SA10 Pa s [%]
Weighting 20% 30% 20% 30%
wall and a local grid refinement of the clearance, as shown in Fig. 3 the
grid of the HF0 model with Medium (M) grid number of 5.9 million was
increased and decreased by a factor to form fine (F) and coarse (C) grid to
assess the effect of grid density on the simulation results. It can be found
that the grid density has very little influence on the pressure head of VAD.
Therefore, the medium grid was chosen as a trade-off between accuracy
and wall-clock time (Table 2).
The pressure differences between the inlet and outlet of VAD under
the three HF models were extracted and compared with the experimental
results of Wu et al. [5]. It can be found that the pressure head obtained in
this study is similar to the results obtained by Wu et al. [5], which proves
the reliability of the method in this study (Table 3).
3. Results
3.1. Platelet trajectory tracking
The trajectory of platelets in the LA, LAA and LV with different vol-
ume sizes, as shown in Fig. 4a, b and 4c, which indicates the complex
pathway of blood within the LA, LAA and LV of HF patients supported
with VAD. The particles of platelets show a tortuous flow characteristic in
LA and LV with different sizes of LV, especially in the LAA and aortic
sinus (AS), where platelet particles travel several times, and finally
platelets move into the inner space of VAD at a relatively high velocity in
which platelets are subjected to the high shear surroundings. With the
expansion of LV volume, the number of platelets entering and exiting the
LAA per unit time gradually decreased, which means that the flowability
of platelets in the LAA diminished, leading to an increase in RT of platelet
particles in the LAA. At the same time, as LV volume increases, the ve-
locity of platelet particles within LV decreases which leads to increasing
in RT for platelet within LV.
Compared to the failure heart, the blood pump with a high-speed
rotor can create significantly faster flow velocities and NPSS, which
bring more severe effects on platelets. As shown in Fig. 4d and e. Velocity
‘hot spots’ were found in the top clearance and secondary flow passage,
implying that this region includes the large velocity gradient and the high
NPSS. The studied VAD is a semi-open impeller, so that the blood with
high kinetic energy, driven by the pressure difference between the suc-
tion surface (SS) and pressure surface (PS) of blades, flows from the
impeller to the narrow top clearance and then moves back to the
Fig. 3. Mesh of the studied model: (a) Mesh of the failure heart (HF0); (b) Mesh of CH-VAD.
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Medicine in Novel Technology and Devices 16 (2022) 100135
Table 2
Grid independence verification.
C–F M-F
Pressure Head Ratio (Relative to the fine mesh) 98.271% 99.456%
Table 3
Simulation accuracy verification.
HF0 HF1 HF2 Reference result [5]
Pressure Head [mmHg] 72.8 72.6 72.8 72.7
impeller, resulting in a high velocity zone appearing in the top clearance.
Meanwhile, to avoid flow stagnation, the secondary flow passage is
usually designed within VAD (Fig. 2b). The blood is accelerated by
impeller and moves into the secondary flow passage, which is a narrow
gap in the studied VAD and makes the velocity of blood further accel-
erated leading to the appearance of a high velocity zone.
3.2. Lagrangian metrics for evaluating thrombogenicity
3.2.1. SA and RT in failure hearts
The distribution of RT and SA for all platelet trajectories in the
different failure heart models is shown in Fig. 5a and b. The mean RT of
platelet particles traversing the failure heart increases with increasing LV
volume, due to a decrease of blood velocity within the LV as the degree of
HF increases (Fig. 4). In these three models, the mean velocity of platelet
particles traversing the largest LV decreased by approximately 160%
compared to the smallest LV (HF0: 0.098 m/s, HF2: 0.062 m/s) and the
mean RT increased by 255% (HF0: 2.316s, HF2: 5.906s). The particles
with RT greater than 5s were defined as the long residence time (LRT)
particles 22 in this study and we found that the proportion of LRT par-
ticles increased (from 5.6% of HF0 to 54.2% of HF2) with the increase of
LV size. The mean SA values were largely insensitive to LV size (Fig. 5d),
but the small LV model (HF0) had longer tails of the SA distribution, with
190% more extreme values in the smallest LV compared to that of the
largest LV (HF0: 8.7 Pa s, HF2: 4.5 Pa s) (Fig. 5b). This is because the
faster velocity of blood in the smaller LV model results in a larger velocity
gradient, which created larger shear stress. Of note, the SA within the HF
heart was well below the threshold for significant platelet activation (10
Pa s [22]). Thus, RT, especially LRT, was the main contributor to
thrombosis formation, while SA contributed very weakly to platelet
activation in the inner space of failure hearts.
3.2.2. SA and RT in VADs
The distribution of RT and SA for platelets navigating the trajectory
within the VAD connected with different failure heart models (HF0, HF1
and HF2), as shown in Fig. 5c and d. The VAD rotor with high rotating
Y. Li et al.
Fig. 4. Platelet trajectory: (a) In the failure heart model of HF0; (b) In the failure heart model of HF1; (c) In the failure heart model of HF2 (d) In VAD and (e) Details in
top clearance.
speed accelerates blood flow (0.098 m/s, 0.083 m/s, 0.061 m/s in failure
heart of HF0, HF1 and HF2 and 1.680 m/s in VAD), which results in the
RT of platelet particles within the VAD was well below not only the mean
RT in failure heart models (2.316s, 3.803s, 5.906s of HF0, HF1 and HF2
in failure heart and 0.114s, 0.111s, 0.111s of HF0, HF1 and HF2 in VAD),
but also the threshold of RT (5s [22]) that leads to thrombosis. Therefore,
the varying degrees of HF had a limited effect on the RT of platelets
within the VAD. The high blood velocity within VAD also led to an in-
crease in SA, and the particles with SA greater than 10 Pa s was defined as
the high stress accumulation (HSA) particles [22]. It can be found that
the SA was much higher than that of failure heart, both on mean value
(0.392 Pa s, 0.378 Pa s, 0.363 Pa s of HF0, HF1 and HF2 in failure heart
and 0.713 Pa s, 0.695 Pa s, 0.701 Pa s of HF0, HF1 and HF2 in VAD) and
the proportion of HSA (0% in failure heart and 0.264%, 0.269%, and
0.264% in VAD of HF0, HF1 and HF2). The changing of LV volume had
little effect on SA in the VAD. In conclusion, compared to failure heart,
thrombus formation within VAD was mainly due to HSA activated
platelets, and the effect of RT was small.
3.2.3. Evaluation of TP
The thrombotic metrics and the assessment of the TP within the
failure heart and VAD system are shown in Tables 4 and 5 respectively.
LRT is mainly contributed by the failure heart (Fig. 5a), while the HSA is
mainly contributed by VAD (Fig. 5c). The combined effects of LRT and
5
Medicine in Novel Technology and Devices 16 (2022) 100135
HSA lead to thrombus formation in the failure heart and VAD system. As
the size of LV volume increases, the percentage of LRT within failure
heart increases (Fig. 5a), whereas, the activation of platelets is consistent
within VAD owing to its constant rotating speed which therefore creates
the same level of NPSS at different LV volumes. Therefore, the TP in-
creases with increasing LV volume during VAD-assisted treatment of
heart failure.
3.3. Eulerian metrics for evaluating thrombogenicity
3.3.1. RT in failure hearts
Based on Lagrangian metrics analysis, LRT is considered an important
cause of thrombus formation in failure heart. Fig. 6 illustrates the dis-
tribution of RT in different HF conditions based on Eulerian metrics
analysis. As the volume of the LV expands, the RT of blood within the
failure heart increases. The potential of thrombus formation in the aortic
sinus (AS) is higher in VAD-assisted heart because the VAD replaces the
ejection function of the heart, which makes it possible for the AS to be
closed completely under fully supported conditions. Blood stagnation in
the LA, especially in the LAA (Fig. 4), is more severe than in the LV. The
loss of contraction for failure heart makes it difficult to drain blood from
the LAA in promptly, which worsens as the degree of HF aggravates,
leading to the higher risk of thrombosis in the LAA.
Y. Li et al. Medicine in Novel Technology and Devices 16 (2022) 100135

Fig. 5. Comparison of platelet trajectories in different HF conditions (The square box depicts the distribution of values less than or equal to the mean; The shaded area
depicts the distribution of values greater than or equal to the threshold; And the black line is the line connecting the means.): (a) Comparison of the RT in failure heart;
(b) Comparison of the SA in failure heart; (c) Comparison of the RT in VAD; (d) Comparison of the SA in VAD.

3.3.2. NPSS in VAD

Table 4
Lagrangian analysis shows that stress accumulation in VAD, that is,
Mean and above-threshold percentage value of RT and SA of particle trajectories
NPSS activates platelets and increases the probability of thrombosis.
within failure heart and VAD.
Fig. 7 illustrates the distribution of NPSS within the VAD based on
RT SA Eulerian metrics analysis. It can be found that the flow field within VAD
Mean RT [s] RT  5s [%] Mean SA [Pa⋅s] SA10 Pa s [%] is filled with high shear stress regions, especially in the secondary flow
HF0 2.43 5.663 1.105 0.264 passage and the top clearance region. The secondary flow passage of the
HF1 3.914 21.925 1.073 0.269 studied VAD was narrow and the blood flow was fast (Fig. 4d), thus
HF2 6.017 54.163 1.064 0.264 generating high velocity gradient and NPSS. While, as the blood moves
into the secondary flow passage, its kinetic energy weakens and the ve-
locity gradient decreases, so the level of NPSS on the inside of the sec-
Table 5 ondary flow passage is lower than on the outside. Meanwhile, the high
Normalized results for the mean and above-threshold percentage value of SA and velocity flow of top clearance brings high velocity gradient, creating a
RT and the assessment of TP within failure heart and VAD. large amount of NPSS regions in top clearance. In conclusion, the narrow
RT SA TP track within VAD results in a larger NPSS and increases the likelihood of
platelets being activated contributing to the risk of thrombosis formation.
Mean RT RT  5s [%] Mean SA SA10 Pa s [%]

HF0 0.000 0.000 1.000 0.000 0.200

4. Discussion
HF1 0.414 0.335 0.220 0.001 0.227
HF2 1.000 1.000 0.000 0.000 0.500
Thrombotic events are the most significant complication in HF pa-
tients and it is important to assess the risk factors for adverse outcomes of
VAD for the treatment of HF. The complicated structure of failure heart

6
Y. Li et al.
Fig. 6. Comparison of RT distribution in different HF model degrees with different size of LV volume assisted by VAD: (a) Failure heart of HF0; (b) Failure heart of
HF1; and (c) Failure heart of HF2.
Fig. 7. Distribution of NPSS in VAD: (a) Distribution of NPSS in the radial plane; (b) Distribution of NPSS in the axial plane.
(left ventricular) and VAD combined with the VAD-created chaos flow
field contribute to the thrombosis formation. It is important for device
optimization and guiding the VAD patient treatment to build a throm-
bosis model for evaluating the thrombosis probability and distribution
within failure heart and VAD. In previous study, the thrombotic risk
model based on Lagrangian features had been proposed to assess the
activation, transport and aggregation of platelets suspended in the blood
to quantify the complex hemodynamic and thrombogenic potential in
cardiovascular devices [25–27]. However, it lacks the quantitative
analysis Euler to compare the thrombotic potential of different models.
Meanwhile, in previous TP methods, the information on platelet trajec-
tories that is smaller than the min value (such as: low SA and short RT)
also be considered an important part of outliers. In fact, the low SA and
short RT has a low impact on thrombus formation. Different from the
work of previous study [22], this study proposed the concept of mean and
threshold values of stress accumulation and residence time in our
thrombosis models to accurately assess the likelihood of thrombus for-
mation. Our thrombosis model establishes the same evaluation criteria in
different study subjects, and improves the impact of the original
thrombus model on the overall accuracy due to the inclusion of outliers
with values smaller than the min. Thus, the thrombus model proposed in
this study may provide a more comprehensive and accurate assessment of
thrombus probability.
In assessing the influence of the volume of LVs on thrombosis, Aliseda
et al. [22]. studied normal and small LVs and found that, compared to
decreased VAD rotating speed, the small LV size is the main pathologic
mechanism responsible for the increased incidence of thrombosis. While,
7
Medicine in Novel Technology and Devices 16 (2022) 100135
how the changing of LV size affects the risk of thrombosis formation in
VAD patients is not clear. In addition, some studies only consider the
hemodynamic surroundings in the LV and ignore the flow features in the
LA, particularly in the LAA which is thought to be a highly thrombogenic
location within failure heart [44]. The interaction between failure heart
blood flow, structure of failure heart and VAD make the assessment of
thrombus formation to be complicated. This study integrates the inter-
action of VAD and failure heart (LV, LA and LAA) to assess the thrombotic
potential within failure heart and VAD more accurately. The combination
of the Lagrangian and Eulerian methods were utilized to assess the as-
sociation between the degree of heart failure (different size of LV)
combined with VAD and thrombotic potential, and to locate
thrombus-prone sites. Lagrangian metrics suggest that, under the same
blood flow rate conditions, compared to other sizes of LV, the HSA can
activate platelets more easily leading to the increasing potential of
thrombosis within the smaller size of LV. However, the value of SA within
failure heart (LV, LA and LAA) is well below the threshold for platelets to
be activated, which therefore makes a smaller contribution to thrombosis
formation. In contrast to HSA, as the size of LV enlarged, the RT of blood
stagnation within failure heart became longer and the proportion of LRT
increased significantly, suggesting that LRT is the main cause of throm-
bosis formation within failure heart. Meanwhile, the areas where LRT
was localized were identified by the Eulerian method in this study. The
LAA was found to be the most affected area for thrombosis formation, in
which the risk of thrombosis elevated with the increasing size of LV.
Clinical studies have shown that the LAA is a common site of thrombosis
formation in HF patients and the risk of thrombosis formation in LAA is
Y. Li et al.
positively correlated with LV diameter, with a prevalence of 40%–68%
[44]. Our study also found that the LRT of blood within the LV increases
as the increasing of LV size, corresponding to clinical studies in which
they found that 11–44% of patients suffer from LV thrombosis [44].
The VAD rotor with a high rotating speed impels blood to pass
through the device in a shorter time (much less than the residence time of
blood stays within the failure heart) and therefore reduces the possibility
of blood stasis. The high rotating speed of the VAD rotor can generate a
large amount of NPSS. Previous studies have shown that platelet acti-
vation is induced when the level of NPSS beyond the value of 100 Pa even
with a very short exposure time (<1 s) [17]. In our study, the Lagrangian
method has shown that the proportion of HSA within VAD is much higher
than that within failure heart. Thus, compared to failure heart, the for-
mation of thrombosis within VAD has been mainly attributed to NPSS.
Employment of the Eulerian method help to identify areas where high
NPSS activates platelet. The high NPSS region within the VAD is found to
be associated with the secondary flow, where the high-velocity blood
moves from the impeller into a narrow space (top clearance and sec-
ondary flow passage) leading to a steep increase of NPSS and increasing
the potential of platelet activation.
In addition, this study shows that the hemodynamics surrounding
failure heart and VAD have a strong influence on the thrombogenic po-
tential. The thrombotic risk associated with platelet activation induced
by the VAD-created NPSS is not negligible. These activated platelets will
enter the AA, further elevating the thrombosis risk. It is important for the
treatment of patients with VADs to investigate the combination effect of
the structure of failure heart (LV, LA and LVV) and VAD, and their he-
modynamic surroundings on thrombosis potential.
This study also has some limitations. First, we only considered the
case of complete heart failure, in which the heart has no contractile ca-
pacity and relies only on the VAD for blood ejection, whereas, the
changes in hemodynamics within failure heart in the case of incomplete
HF and the effect on VAD blood compatibility still need to be paid
attention. Second, the effects of heart valves and aortic valves were
ignored, and it was considered that in the case of complete VAD assist,
the aortic valves were completely closed while the heart valves were
completely open. Third, this study employed the frozen rotor method for
steady-state simulation, and the rotor was fixed in the simulation.
Therefore, the platelet trajectories obtained in this paper are not real path
lines. Finally, under VAD pumping conditions, the blood is considered to
a homogeneous Newtonian fluid, but in fact, there are still some regions
in failure heart with shear rates below 100/s, which is the state between
the Newtonian and non-Newtonian fluid [37,45].
5. Conclusion
In this paper, CFD methods were employed to investigate the effect of
different left ventricle (LV) volumes on the thrombotic performance of
failure heart and ventricular assist device (VAD). Lagrangian methods
were employed to obtain information on platelet voyage trajectories, the
concepts of mean and threshold were introduced to accurately assess the
likelihood of thrombus occurrence, and Eulerian methods were
employed to identify the thrombus-prone locations. The results showed
that residence time (RT) was the main cause of thrombus within failure
heart, and the percentage of platelet trajectories exceeding the RT
threshold increased significantly with increasing LV volume. As the size
of LV volume increases, the RT increases in the LAA and LV, which
indicated that thrombi tend to form here. NPSS-induced platelet activa-
tion is the main cause of thrombus generation within VAD. The high
NPSS in the narrow regions (top clearance and secondary flow passage)
within the VAD implies a higher risk of thrombosis. The finding of this
study can be used to guide the clinical treatment of VAD patients and
optimize the design of VAD for reducing the thrombosis risk.
8
Medicine in Novel Technology and Devices 16 (2022) 100135
Funding sources
This work was supported by the National Key R&D Program of China
(Grant no. 2020YFC0862900, 2020YFC0862902, 2020YFC0862904 and
2020YFC0122203), the Beijing Municipal Science and Technology
Project (Grant no. Z201100007920003) and the National Natural Sci-
ence Foundation of China (Grant no. 32071311) and Key R&D project of
Shanxi Province (Grant no. 201903D321149).
Author contribution to study
Yuan LI: Conceptualization; Data curation; Formal analysis; Investi-
gation; Methodology; Validation; Roles/Writing - original draft; Writing -
review & editing. Yifeng XI: Investigation; Software; Validation; Writing -
review & editing. Hongyu WANG: Investigation; Validation; Writing -
review & editing. Anqiang SUN: Funding acquisition; Project adminis-
tration; Resources; Supervision. Xiaoyan DENG: Funding acquisition;
Project administration; Resources; Supervision. Zengsheng CHEN:
Conceptualization; Funding acquisition; Methodology; Project adminis-
tration; Resources; Software; Supervision; Validation; Roles/Writing -
original draft; Writing - review & editing. Yubo FAN: Funding acquisi-
tion; Project administration; Supervision.
Declaration of competing interest
The authors declare that there are no conflicts of interest.
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