Computer Methods and Programs in Biomedicine 197 (2020) 105763
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Computer Methods and Programs in Biomedicine journal homepage: www.elsevier.com/locate/cmpb
Biomechanical effects of the novel series LVAD on the aortic valve Bin Gao a,∗, Yizhou Kang a, Qi Zhang b, Yu Chang a a b
School of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, PR China National Energy Conservation Center, Beijing, PR China
a r t i c l e
i n f o
Article history: Received 11 June 2020 Accepted 14 September 2020
Keywords: Fluid–structure interaction Aortic valve LVAD Hemodynamics Biomechanical states
a b s t r a c t Background and Objective: The series type of LVAD (i.e., BJUT-II VAD) is a novel left ventricular assist device, whose effects on the aortic valve remain unclear. Methods: The biomechanical effects of BJUT-II VAD on the aortic valve were investigated by using a fluid–structure interaction method. The geometric model of BJUT-II VAD was virtually implanted into the ascending aorta to generate the realistic flow pattern for the aortic valve (i.e., support). In addition, the biomechanical states of the aortic valve without BJUT-II VAD support was computed as control (i.e., control case). Results: Results demonstrated that the biomechanical effects of BJUT-II VAD were quite different from that resulting from traditional “bypass LVAD.” Compared with those in the control case, BJUT-II VAD support could significantly reduce the stress load of the leaflet (maximum stress, 0.5 MPa in the control case vs. 0.12 MPa in the support case). Similarly, the rapid valve opening time (100 ms in the control case vs. 175 ms in the support case) and rapid valve closing time (50 ms in the control case vs. 150 ms in the support case) in the support case were obviously longer than those in the control case. Moreover, BJUT-II VAD support reduced retrograde blood flow during the diastolic phase and significantly changed the distribution of WSS of the leaflets. Conclusions: In summary, while unloading the left ventricle, BJUT-II VAD could provide beneficial biomechanical states for the aortic leaflets, thereby reducing the risk of aortic valve disease. © 2020 Elsevier B.V. All rights reserved.
1. Introduction Left ventricular assist devices (LVADs) are one of the important treatments used for patients with heart failure [1]. Currently, LVADs employed in clinical practice are all in parallel with the native left ventricle of patients. This kind of LVADs is called “bypass LVAD,” whose inlet cannula and outlet cannula are anastomosed with the left ventricle and ascending aorta, respectively [2]. Given the parallel relationship between LVAD and left ventricle, the “bypass LVAD” gradually exposes some problems in clinical application. Maradey et al. demonstrated that LVAD support results in patients having prolonged ventricular arrhythmias because of the destruction of the intact structure of the left ventricle by the inlet cannula of the “bypass LVAD” [3]. Rosenbaum et al. reported that the “bypass LVAD” support can obviously enlarge the left ventricular afterload [4], which might further impair myocardial function. Patel et al. found that the infection resulting from the driveline is ∗
Corresponding author. E-mail address: [email protected] (B. Gao).
https://doi.org/10.1016/j.cmpb.2020.105763 0169-2607/© 2020 Elsevier B.V. All rights reserved.
the most common adverse effect in patients supported with “bypass LVAD” [5]. Moreover, the normal structure and function of the aortic valve and aortic root have been found to be impaired by the “bypass LVAD,” resulting in aortic valve insufficiency [6] or commissural fusion of the leaflets [7]. To solve this problem, a novel “series LVAD, namely, BJUT-II VAD, has been proposed by our group [8]. The “series LVAD” is placed into the ascending aorta to eliminate the inlet and outlet cannulae, which maintain the normal structure of the left ventricle (Fig. 1A). The percutaneous driveline of BJUT-II VAD is also eliminated to avoid infection caused by percutaneous wire. It is driven by an extracorporeal dynamic system [9]. As the special anatomical location, the hemodynamic effects of BJUT-II VAD on the aorta have been studied. Xuan et al. found that BJUT-II VAD can disturb the blood flow pattern in the aortic arch [10]. Gao et al. reported that the hemodynamic effects resulting from the BJUT-II VAD mode are obviously different from that of the “bypass LVAD” [11]. Subsequently, Gu et al. proposed that the phase difference between BJUT-II VAD and native left ventricle significantly changes the hemodynamic states of the aorta [12]. Similarly, Zhang
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Computer Methods and Programs in Biomedicine 197 (2020) 105763
Fig. 1. Geometric model and boundary condition. (A) Schematic of BJUT-II VAD. (B) The whole geometric model of the aortic valve with BJUT-II VAD. (C, D) The geometric model of the leaflets. (E) The lumped parameter model of the cardiovascular system without BJUT-II VAD support. (F) The lumped parameter model of the cardiovascular system with BJUT-II VAD support. (G) The waveforms of the LVP and AP used in the control case. (H) The waveform of the LVP and AP used in the support case. NC, noncoronary leaflet. RC, right coronary leaflet; LC, left coronary leaflet; LVP, left ventricular pressure; AP, arterial pressure.
et al. reported that BJUT-II VAD support also affects aortic swirling flow characteristics [13] and intra-ventricular flow pattern [14]. Although the above studies demonstrated that BJUT-IIVAD support can obviously change the hemodynamic environment of the aorta and the left ventricle, and these changes were significantly different from that caused by the “bypass LVAD,” the biomechanical effect of BJUT-II VAD on the aortic valve is unclear. To clarify the biomechanical mechanism of BJUT-II VAD support on the aortic valve, a numerical study employing the “fluidstructure interaction” (FSI) approach was conducted. The realistic geometric model of BJUT-II VAD was virtually placed into the aortic geometric model. The realistic blood flow field of BJUT-II VAD was generated by the rotation of the impeller. The kinematic characteristics, principal stress distribution, blood flow pattern, and wall shear stress (WSS) distribution on the leaflets were chosen as the biomechanical indicators.
2. Methods 2.1. Description of the geometric model The geometric model (support case) consisted of two parts: aortic valve and BJUT-II VAD (Fig. 1B). The aortic valve model was constructed based on a previous study [15]. The model included four parts: the ascending aorta, the aortic sinus, three leaflets, and left ventricular outflow tract. The leaflets were located between the left ventricular outflow tract and the ascending aorta. According to the clinical data, the diameter of the ascending aorta was 20 mm. The thickness of the leaflets was 0.5 mm to reduce the computational cost. On the basis of the geometric relationship between the leaflets and the aortic sinus [16], the width of the leaflets is equal to 1/3 of the perimeter of the sinus junction. Thus, the width of the leaflets in this work was 20 mm. In this study, the three
2
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Computer Methods and Programs in Biomedicine 197 (2020) 105763
leaflets were named the non-coronary leaflet (NC), right coronary leaflet (RC), and left coronary leaflet (LC) (Fig. 1C). The area where the leaflets were in contact with the vessel was named the leaflet commissure (Fig. 1D). The model of BJUT-II VAD was virtually placed into the ascending aorta, including the inducer blade, the impeller, and the diffuser blade (Fig. 1B, green parts). As the housing of BJTU-II VAD is close to the wall of ascending aorta, it was ignored here. In clinical practice, the inducer blade and the diffuser blade are stationary, while the impeller rotates around this axis in a counterclockwise direction. The blood is pumped by the rotating impeller from the left ventricle to the aorta. The model comprises one inlet and one outlet, namely, the ventricular inlet and the aortic outlet. Given that this study aimed to investigate the biomechanical effects of “series LVAD” on the aortic valve, the deformation of the aortic wall was ignored here. The model (control case), including the aortic model, was established as the control group.
2.4. Discretization of the FSI model The discretization strategy in this study was the same as in our previous study. The leaflets were discretized by 10-node quadratic tetrahedral elements (C3D10). The results of the previous study revealed that 20,352 elements were sufficient to obtain accurate biomechanical states. To accurately discretize the fluid domain, the octree lattice structure, providing high-order spatial discretization for the blood domain, was employed. As the geometric size of the fluid domain was similar to that of previous studies [15, 17], the lattice size determined in the previous work was used to discretize the fluid domain (0.3 mm). The number of lattices of the control case and the support case was 0.87 and 0.63 million, respectively. 2.5. Boundary conditions The biomechanical states and hemodynamic states of the aortic valve with or without BJUT-II VAD support were investigated. The case consisting of the aortic valve and BJUT-II VAD was named the support case, while the case that only included the aortic valve was named the control case. The boundary conditions of both cases were generated from the lumped parameter model [11] (Fig. 1E and 1F). This mode includes four parts, namely, the left atrium, left ventricle, BJUT-II VAD, and systemic circulation. The left ventricular pressure (LVP) and the arterial pressure (AP) were calculated as the boundary condition. LVP was used as the pressure inlet boundary condition, and AP was employed as the outlet pressure boundary condition. For the control case, the hemodynamic states of the healthy people were reproduced, as shown in Fig. 1G. For the support case, the support level of BJUTII VAD was regulated to allow the aortic valve to open periodically (Fig. 1H), in which the rotational speed of the impeller was 60 0 0 rpm. To illustrate the turbulent flow pattern in BJUT-II VAD and in the aortic root, the wall-adapting local eddy viscosity model [15] was applied, which has been proven to be able to accurately describe the near wall behavior of fluid [28].
2.2. Lattice Boltzmann theory The details of the lattice Boltzmann (LBM) approach employed in this study have been described previously [17], and only a simple explanation is shown here. LBM is a mesoscopic method from statistical physics to simulate flow problems [18]. In this study, the Bhatnagar–Gross–Krook model was employed. The governing equation could be described as in Eq. (1):
fi (x + δt ei , t + δt ) − fi (x, t ) = −
1
τ
fi (x, t ) − fieq (x, t )
(1)
where the local equilibrium distribution function is shown as Eq. (2)
fieq = ωi ρ 1 +
u·u ei · u ( ei · u ) + − Cs2 2Cs4 2Cs2 2
(2)
In these equations, fi is the density distribution function. It indicates the fraction of the particles moving with the lattice velocity i. τ represents the relaxation time of the particles. ei denotes the discrete microscopic velocity. Cs is the speed of sound. The density ρ and velocity u are represented as Eqs. (3) and (4):
ρ=
fi
2.6. Biomechanical index The distribution of principal stress, mean stress, and radial displacement (RD) was calculated. The mean stress [15] was calculated to reflect the changes in the average level of principal stress with time, as illustrated in Eq. (7):
(3)
i
ρu =
f i ei
(4)
i
stressm =
The kinematic viscosity is expressed as
τ μ = Cs2 ( − 0.5 ) t
(5)
2.3. Finite element model of the leaflets
RDm (t ) =
To describe the biomechanical property of the leaflets, the isotropic, hyperelastic incompressible, second-order Ogden model was employed based on a previous study [17]. The constitutive equation of the leaflets is reflected by Eq. (6): N 2μi ¯ αi ¯ αi ¯ αi (λ1 + λ2 + λ3 − 3 ) 2 i=1
αi
(7)
where stressm denotes the volume average principal stress, stressi represents the stress of the ith element, and voli is the volume of the ith element. The RD [17] reflects the change in the spatial position of the valve with time, and it is expressed by Eq. (8):
In this paper, the constant kinematic viscosity was used to determine the relaxation time. Moreover, the lattice model named C3D27 (3D model with 27 directional vectors) was employed.
W =
stressi ∗ voli voli
(xm (t ) − xo )2 + (zm (t ) − zo )2
(8)
where RDm is the radial displacement of the midpoint of the free edge of the leaflets (unit mm). xm (t) and zm (t) represent the spatial coordinates of the midpoint at t time. xo and zo denote the spatial coordinates of the original point.
(6)
3. Results
where W represents the strain energy function of the leaflet. λi indicates principal strain. α i and μi denote the material parameters. According to the previous work of our group [15], α 1 = 67.74, α 2 = 27.47, μ1 = 19.58kPa, and μ2 = 260.56kPa. In addition, the density of the leaflet is 1100 kg/m3 .
In this study, three time points, namely, peak systole, peak diastole, and middle point of the rapid closing period, were chosen to extract the results. The distribution of stress, the mean stress, the radial displacement, the blood flow pattern, and the WSS distribution are illustrated in Figs. 2–5. 3
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Fig. 2. Stress distribution in the two cases.
3.1. Stress distribution of the leaflets
When the left ventricle began to relax, the mean stress increased rapidly with the increase in transvalvular pressure. Moreover, the waveforms of the three leaflets were consistent. Therefore, the biomechanical environment of the three leaflets in the control case was consistent with one another. During the rapid closing phase, an obvious concussion phenomenon in the mean stress curve of the leaflet was observed (region a). By contrast, the biomechanical environment of the leaflets in the support case was quite different from that in the control case. Fig. 3B shows the waveform of the mean stress of leaflets in the support case. Compared with that in the control case, the mean stress in the support case was obviously lower (maximum mean stress, 0.26 MPa in the control case vs. 0.03 MPa in the support case). In addition, the mean stress curves of the three leaflets were not consistent with one another. Thus, the biomechanical environment of the three leaflets in the support case was quite different from that in the control case. Moreover, no concussion phenomenon in the mean stress curve was found in the support case (region b). Fig. 3C and 3D illustrate the waveforms of RD in the two cases. In the control case, the waveforms of the RD of the three leaflets were consistent with one another (region c; Fig. 3C). The rapid valve opening time (RVOT) and rapid valve closing time (RVCT) were 100 and 50 ms, respectively. This result was in agreement with the findings reported by Kemp [19]. The obvious concussion was observed at the end of the rapid closing phase (region d). In the support case, the waveforms of the RD of the three leaflets were quite different from one another (region c; Figure D). RVOT
Fig. 2 illustrates the principal stress distribution of leaflets in the control case and the support case. During the systolic period, the principal stress distribution of the leaflet in both cases was similar to each other. At the peak systole, the aortic valve in both cases was fully opened. In both cases, the high stress regions were located at the free edge near the leaflet commissure (region a). However, during the diastolic period, the stress distribution in the support case was obviously different from that in the control case. For the control case, the aortic valve was fully closed, and the high stress region was located at the leaflet commissure and the belly area of the leaflet (regions b and c). However, for the support case, the aortic valve was not fully closed, and the stress distribution was more uniform than that in the control case. The level of the principal stress of the leaflet in the control case was obviously larger than that in the support case. The peak values of the stress in the control case and the support case were 0.5 and 0.12 MPa, respectively. 3.2. Dynamic characteristics of the leaflets The dynamic characteristics of the leaflets in the two cases were evaluated by utilizing the mean stress and radial displacement (Fig. 3). Fig. 3A shows the waveform of the mean stress in the control case. During the systolic period, the mean stress rapidly decreased with the decrease in the transvalvular pressure (0–0.3s). 4
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Fig. 3. Changes in the kinematic characteristics and biomechanical states in the two cases. (A) The waveform of the mean stress during the whole cardiac period in the control case. (B) The waveform of the mean stress under BJUT-II VAD support. (C) The waveform of the radial displacement of the leaflets without BJUT-II VAD support. (D) The waveform of the mean stress under BJUT-II VAD support.
and RVCT were about 175 ms and larger than 150 ms, respectively. Notably, during the diastolic period, significant differences were observed in the moving trajectories of the three leaflets. Moreover, the RD of the leaflets in the control case was significantly lower than that in the support case during the diastolic period. Thus, the aortic valve was not fully closed in the support case.
c). In addition, as the aortic valve could not be closed instantly, obvious reverse flow was observed (region d), which is consistent with a previous study [20]. However, in the support case, the level of retrograde blood flows was lower than that in the control case. Thus, the level of retrograde flow, which flowed into the aortic sinus (region c) and left ventricle (region d), was also lower in the support case than in the control case.
3.3. Blood flow pattern in both cases 3.4. WSS distribution Fig. 4 shows the blood velocity vector. To evaluate the difference in blood flow pattern between the two cases, the peak systole and the midpoint of the rapid closing phase were chosen to extract the blood flow velocity vector. At the peak systole, the aortic valve was fully opened in the two cases. In the control case, the high blood velocity region appeared in the middle of the ascending aorta. In addition, the vortex was observed in the aortic sinus (region a) and sinotubular junction (region b). In the support case, the value of the blood velocity through the aortic valve was lower than that in the control case (1.05 m/s in the control case vs. 0.60 m/s in the support case). Blood flow in the aortic sinus flowed into the ascending aorta (region a), and no vortex was found in the sinotubular junction (region b). At the midpoint of the rapid closing phase, the flow pattern in the two cases was quite different from each other. In the control case, obvious retrograde blood flow appeared in the ascending aorta. Obvious retrograde blood flowed into the aortic sinus, which benefitted coronary perfusion (region
Fig. 5 illustrates the WSS distribution in the two cases at three time points (peak systole, midpoint of rapid closing phase, and peak diastole). The distribution of WSS of the leaflets in the control case was different from that in the support case. At peak systole, the high WSS region in the control case was located at the free edges (region a), while the high WSS region in the support case was observed at the belly areas (region b). The value of WSS in the control case was lower than that in the support case (maximum WSS, 7.0 Pa in the control case vs. 12 Pa in the support case). At the midpoint of the closing phase, the high WSS region in the control case was located at the ventricular side of the leaflet (region c), as the high velocity retrograde blood flow flushed the leaflets. The WSS distribution of the three leaflets in the control case was consistent with one another. However, the high WSS region in the support case was located at the free edge of the leaflets and at the belly of the aortic sides of the leaflets (region c). 5
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Fig. 4. Blood velocity vector in the two cases.
Besides, the WSS distribution of the three leaflets in the support case was not consistent with one another. In addition, the level of WSS in the control case was larger than that in the support case (maximum WSS in the control case was 15 Pa vs. that in the support case was 11Pa). At peak diastole, the area of the high WSS region in the control case was larger than that in the support case (region d).
ometric model of BJUT-II VAD was virtually placed into the ascending aorta to generate a realistic hemodynamic environment. The biomechanical states of the aortic leaflets with and without BJUT-II VAD support were calculated by combining the LBM and FE method. To our knowledge, this study is the first to investigate the biomechanical effects of the novel “series LVAD” on the aortic valve. The results demonstrated that the implantation of BJUTII VAD significantly changed the hemodynamic environment of the aortic root and the biomechanical states of the aortic leaflets. Compared with the control case, BJUT-II VAD support could obviously reduce the level of stress of the leaflet. Moreover, compared with support by the traditional “bypass LVAD,” BJUT-II VAD support
4. Discussion In this study, the biomechanical effects of BJUT-II VAD on the aortic valve were investigated by using the FSI method. The ge6
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Fig. 5. Distribution of WSS in the two cases.
could maintain the aortic valve opening periodically, which may prevent valve disease. The stress load on the leaflets has been confirmed as an important reason for the remodeling of the aortic valve. For instance, Weston et al. reported that an increase in the stress of leaflets can reduce the expression of the alpha-smooth muscle actin (α -SMA) [21]. Similarly, Huang et al. found that α -SMA expressed by interstitial cells is regulated by mechanical stress [22]. Bogdanova et al. recently proposed that mechanical stress can promote the expression of osteogenic genes in interstitial cells, which might be a potential reason for aortic valve calcification [23]. In short, previous studies demonstrated that excessive stress load can promote the remodeling of the aortic leaflets. According to a previous study, the transvalvular pressure gradients of the aortic valve increase as the “bypass LVAD” support level increases [24]. The stress load of leaflets would then increase accordingly. Therefore, reducing the impact of LVAD on aortic leaflet stress level has become the direction of future research. Although our group previously demon-
strated that regulating the work mode of “bypass LVAD” can alleviate the effect of “bypass LVAD” support on the stress of the leaflets to some extent [15], the stress load of leaflet with LVAD support is still obviously higher than that in healthy condition [17]. However, the present study demonstrated that the biomechanical effects of BUJUT-II VAD on the aortic valve were quite different from that of “bypass LVAD.” The stress load on the aortic leaflets in the support case was significantly lower than that in the control case (Figs. 2, 3A, and 3B). Thus, BJUT-II VAD could not only achieve perfusion but also significantly reduce the stress load of the valve, thereby playing a good role in maintaining the biomechanical properties of the valve. Clinical studies found that “bypass LVAD” support can enlarge the diameter of the aortic root [6, 7]. Pressure in the aortic root increases with the increase in the support level of BJUT-II VAD, resulting in active root dilatation, which leads to aortic valve insufficiency. However, this complication could be effectively avoided by the series LVAD. We found that the stress load on the leaflet 7
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was reduced with the use of the BJUT-II VAD support. Given that the inlet of BJUT-II VAD is located near the aortic root, BJUT-II VAD could reduce the pressure in the aortic root. Therefore, “series LVAD” can effectively prevent aortic root dilation. According to a previous clinical study, after “bypass LVAD” implantation, the closing duration of the aortic valve increases significantly with the increase in the LVAD support level [28]. Researchers demonstrated that the failure to maintain aortic valve periodic opening induces commissural fusion of the aortic valve leaflets [25]. BJUT-II VAD could significantly change the dynamic characteristics of the leaflets during the rapid opening phase and the rapid closing phase (Fig. 3C and 3D). Compared with that in the control case, the RVOT in the support case was significantly prolonged (100 ms in the control case vs. 175 ms in the support case). BJUT-II VAD is a kind of continuous flow LVAD, so during the whole cardiac cycle, blood is continuously pumped from the left ventricle, thereby reducing the left ventricular preload. In accordance with the Frank–Starling law [26], the myocardial contractile force would decrease with the decrease in the left ventricular preload, resulting in the reduction of the LVP at the systolic phase. Similarly, the RVCT of the leaflets in the support case was obviously larger than that in the control case. The transvalvular pressure gradient of the aortic valve during the diastolic phase was obviously reduced by BJUT-II VAD support. These results demonstrated that the aortic valve could open periodically after “series LVAD” implantation, thereby reducing the risk of aortic valve disease. From the curves of the RD of the leaflets, we found significant differences in the motion trajectories of the three leaflets with the implantation of BJUT-II VAD (Fig. 3D). The rotation of the impeller of BJUT-II VAD affected the blood flow pattern around the leaflets, which in turn changed the dynamic characteristics of the three leaflets. This result was also confirmed from the distribution of WSS (Fig. 5). The distribution of WSS in the control case was consistent with each other, while obvious differences in the distribution of WSS were observed in the support case. Local blood flow pattern around the three leaflets differed. This phenomenon suggested that the influence of BJUT-II VAV on the flow pattern included not only the downstream of aorta but also the aortic root. This abnormal flow pattern may lead to the remodeling of the leaflets and the aortic wall [27]. The effects of “series LVAD” on coronary perfusion are a controversial issue. As the inlet of the “series LVAD” is close to the entrance of coronary artery, which is located in the aortic sinus, coronary perfusion may be reduced with the support of the “series LVAD.” This problem was confirmed by the results of this study. After BJUT-II VAD was implanted, the retrograde blood flow during the diastolic phase was significantly reduced (Fig. 4 region c), which then reduced the amount of coronary perfusion. However, whether this decrease in coronary perfusion would necessarily lead to insufficient blood supply to the heart is unknown. Although BJUT-II VAD support reduces the coronary perfusion, cardiac work is also significantly reduced by BJUT-II VAD support. Thus, coronary perfusion and cardiac oxygen consumption can reach a new balance. This phenomenon suggested that we need to pay attention to the regulation of the support level of “series LVAD” and choose an appropriate unloading level to prevent the excessive reduction of coronary blood flow.
the biomechanical effects of BJUT-II VAD were quite different from those resulting from traditional “bypass LVAD.” Compared with those in the control case, BJUT-II VAD support could significantly reduce the stress load of the leaflet (maximum stress, 0.5 MPa in the control case vs. 0.12 MPa in the support case). Similarly, the rapid valve opening time (100 ms in the control case vs. 175 ms in the support case) and rapid valve closing time (50 ms in the control case vs. 150 ms in the support case) in the support case were obviously longer than those in the control case. Moreover, BJUT-II VAD support reduced the retrograde blood flow during the diastolic phase and significantly changed the distribution of WSS of the leaflets. In short, while unloading the left ventricle, BJUTII VAD could provide beneficial biomechanical states for the aortic leaflets, thereby reducing the risk of aortic valve disease. Declaration of Competing Interest None. Acknowledgements including declarations Funding: This study was partly funded by the National Natural Science Foundation of China (Grant Nos. 61931013, 11832003 and 11602007), the Key Research and Development Program (2017YFC0111104), New Talent (0150 0 05141180 02) and Youth Top Talent training Program (CIT&TCD201904025). References [1] JA. Friedman, Experiences of left ventricular assist device-destination therapy recipients: a systematic review and meta-synthesis, Heart Lung (2020) S0147-9563(20)30084-4. [2] Y Vaidya, S Patibandla, AS Dhamoon, Left Ventricular Assist Devices (LVAD), StatPearls. Treasure Island (FL): StatPearls Publishing, 2020. [3] JA Maradey, MJ Singleton, TJ O’Neill, et al., Management of ventricular arrhythmias in patients with LVAD, Curr. Opin. Cardiol. 35 (3) (2020) 289-294. [4] AN Rosenbaum, AL Clavell, JM Stulak, A Behfar, Correction of high afterload improves low cardiac output in patients supported on left ventricular assist device therapy, ASAIO J. (2020) 10.1097/MAT.0 0 0 0 0 0 0 0 0 0 0 01159. [5] CB Patel, L Blue, B Cagliostro, et al., Left ventricular assist systems and infection-related outcomes: a comprehensive analysis of the MOMENTUM 3 trial, J. Heart Lung Transplant (2020) S1053-2498(20):31428-5. [6] NM Fine, SJ Park, JM Stulak, et al., Proximal thoracic aorta dimensions after continuous-flow left ventricular assist device implantation: longitudinal changes and relation to aortic valve insufficiency, J. Heart Lung Transplant 35 (4) (2016) 423-432. [7] N Bouabdallaoui, I El-Hamamsy, M Pham, et al., Aortic regurgitation in patients with a left ventricular assist device: a contemporary review, J. Heart Lung Transplant 37 (11) (2018) 1289-1297. [8] Y Chang, B. Gao, Modeling and identification of an intra-aorta pump, ASAIO J. 56 (6) (2010) 504-509. [9] Y Chang, B. Gao, A global sliding mode controller design for an intra-aorta pump, ASAIO J. 56 (6) (2010) 510-516. [10] Y Xuan, Y Chang, K Gu, B Gao, Hemodynamic simulation study of a novel intra-aorta left ventricular assist device, ASAIO J. 58 (5) (2012) 462-469. [11] B Gao, Y Chang, Y Xuan, Y Zeng, Y Liu, The hemodynamic effect of the support mode for the intra-aorta pump on the cardiovascular system, Artif. Organs 37 (2) (2013) 157-165. [12] K Gu, B Gao, Y Chang, Y Zeng, The hemodynamic effect of phase differences between the BJUT-II ventricular assist device and native heart on the cardiovascular system, Artif. Organs 38 (11) (2014) 914-923. [13] Q Zhang, B Gao, Y Chang, Effect of different rotational directions of bjut-ii vad on aortic swirling flow characteristics: a primary computational fluid dynamics study, Med. Sci. Monit. 22 (2016) 2576-2588. [14] Q Zhang, B Gao, Y Chang, Computational analysis of intra-ventricular flow pattern under partial and full support of BJUT-II VAD, Med. Sci. Monit. 23 (2017) 1043-1054. [15] B Gao, Q Zhang, Y Chang, Hemodynamic effects of support modes of LVADs on the aortic valve, Med. Biol. Eng. Comput. 57 (12) (2019) 2657-2671. [16] L De Kerchove, M Momeni, G Aphram, et al., Free margin length and coaptation surface area in normal tricuspid aortic valve: an anatomical study, Eur. J. Cardiothorac. Surg. 53 (5) (2018) 1040-1048. [17] B Gao, Q. Zhang, Biomechanical effects of the working modes of LVADs on the aortic valve: a primary numerical study, Comput. Methods Programs Biomed. 193 (2020) 105512. [18] YW Kim, JY Moon, WJ Li, et al., Effect of membrane insertion for tricuspid regurgitation using immersed-boundary lattice Boltzmann method, Comput. Methods Programs Biomed. 191 (2020) 105421.
5. Conclusion In this study, the biomechanical effects of the novel “series LVAD” (BJUT-II VAD) support on the aortic valve were investigated by the FSI approach. The geometric model of BJUT-II VAD is virtually implanted into the ascending aorta to generate the realistic flow pattern for the aortic valve. Results demonstrated that 8
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[19] I Kemp, K Dellimore, R Rodriguez, et al., Experimental validation of the fluid-structure interaction simulation of a bioprosthetic aortic heart valve, Australas Phys. Eng. Sci. Med. 36 (3) (2013) 363–373. [20] R Toninato, J Salmon, FM Susin, A Ducci, G Burriesci, Physiological vortices in the sinuses of Valsalva: an in vitro approach for bio-prosthetic valves, J. Biomech. 49 (13) (2016) 2635-2643. [21] MW Weston, AP. Yoganathan, Biosynthetic activity in heart valve leaflets in response to in vitro flow environments, Ann. Biomed. Eng. 29 (9) (2001) 752-763. [22] HY Huang, J Liao, MS Sacks, In-situ deformation of the aortic valve interstitial cell nucleus under diastolic loading, J. Biomech. Eng. 129 (2007) 880–889. [23] M Bogdanova, A Kostina, K Zihlavnikova Enayati, et al., Inflammation and mechanical stress stimulate osteogenic differentiation of human aortic valve interstitial cells, Front Physiol. 9 (2018) 1635. [24] J Holtz, J. Teuteberg, Management of aortic insufficiency in the continuous flow left ventricular assist device population, Curr. Heart Fail Rep. 11 (1) (2014) 103-110.
[25] M Hatano, K Kinugawa, T Shiga, et al., Less frequent opening of the aortic valve and a continuous flow pump are risk factors for postoperative onset of aortic insufficiency in patients with a left ventricular assist device, Circ. J. 75 (5) (2011) 1147-1155. [26] K Fukamachi, A Shiose, A Massiello, et al., Preload sensitivity in cardiac assist devices, Ann. Thorac. Surg. 95 (1) (2013) 373-380. [27] X Wang, J Lee, M Ali, J Kim, CMR Lacerda, Phenotype transformation of aortic valve interstitial cells due to applied shear stresses within a microfluidic chip, Ann. Biomed. Eng. 45 (10) (2017) 2269-2280. [28] B Gao, Q. Zhang, Biomechanical effects of the working modes of LVADs on the aortic valve: a primary numerical study, Comput. Methods Programs Biomed. 193 (2020) 105512.
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Computer Methods and Programs in Biomedicine journal homepage: www.elsevier.com/locate/cmpb
Biomechanical effects of the novel series LVAD on the aortic valve Bin Gao a,∗, Yizhou Kang a, Qi Zhang b, Yu Chang a a b
School of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, PR China National Energy Conservation Center, Beijing, PR China
a r t i c l e
i n f o
Article history: Received 11 June 2020 Accepted 14 September 2020
Keywords: Fluid–structure interaction Aortic valve LVAD Hemodynamics Biomechanical states
a b s t r a c t Background and Objective: The series type of LVAD (i.e., BJUT-II VAD) is a novel left ventricular assist device, whose effects on the aortic valve remain unclear. Methods: The biomechanical effects of BJUT-II VAD on the aortic valve were investigated by using a fluid–structure interaction method. The geometric model of BJUT-II VAD was virtually implanted into the ascending aorta to generate the realistic flow pattern for the aortic valve (i.e., support). In addition, the biomechanical states of the aortic valve without BJUT-II VAD support was computed as control (i.e., control case). Results: Results demonstrated that the biomechanical effects of BJUT-II VAD were quite different from that resulting from traditional “bypass LVAD.” Compared with those in the control case, BJUT-II VAD support could significantly reduce the stress load of the leaflet (maximum stress, 0.5 MPa in the control case vs. 0.12 MPa in the support case). Similarly, the rapid valve opening time (100 ms in the control case vs. 175 ms in the support case) and rapid valve closing time (50 ms in the control case vs. 150 ms in the support case) in the support case were obviously longer than those in the control case. Moreover, BJUT-II VAD support reduced retrograde blood flow during the diastolic phase and significantly changed the distribution of WSS of the leaflets. Conclusions: In summary, while unloading the left ventricle, BJUT-II VAD could provide beneficial biomechanical states for the aortic leaflets, thereby reducing the risk of aortic valve disease. © 2020 Elsevier B.V. All rights reserved.
1. Introduction Left ventricular assist devices (LVADs) are one of the important treatments used for patients with heart failure [1]. Currently, LVADs employed in clinical practice are all in parallel with the native left ventricle of patients. This kind of LVADs is called “bypass LVAD,” whose inlet cannula and outlet cannula are anastomosed with the left ventricle and ascending aorta, respectively [2]. Given the parallel relationship between LVAD and left ventricle, the “bypass LVAD” gradually exposes some problems in clinical application. Maradey et al. demonstrated that LVAD support results in patients having prolonged ventricular arrhythmias because of the destruction of the intact structure of the left ventricle by the inlet cannula of the “bypass LVAD” [3]. Rosenbaum et al. reported that the “bypass LVAD” support can obviously enlarge the left ventricular afterload [4], which might further impair myocardial function. Patel et al. found that the infection resulting from the driveline is ∗
Corresponding author. E-mail address: [email protected] (B. Gao).
https://doi.org/10.1016/j.cmpb.2020.105763 0169-2607/© 2020 Elsevier B.V. All rights reserved.
the most common adverse effect in patients supported with “bypass LVAD” [5]. Moreover, the normal structure and function of the aortic valve and aortic root have been found to be impaired by the “bypass LVAD,” resulting in aortic valve insufficiency [6] or commissural fusion of the leaflets [7]. To solve this problem, a novel “series LVAD, namely, BJUT-II VAD, has been proposed by our group [8]. The “series LVAD” is placed into the ascending aorta to eliminate the inlet and outlet cannulae, which maintain the normal structure of the left ventricle (Fig. 1A). The percutaneous driveline of BJUT-II VAD is also eliminated to avoid infection caused by percutaneous wire. It is driven by an extracorporeal dynamic system [9]. As the special anatomical location, the hemodynamic effects of BJUT-II VAD on the aorta have been studied. Xuan et al. found that BJUT-II VAD can disturb the blood flow pattern in the aortic arch [10]. Gao et al. reported that the hemodynamic effects resulting from the BJUT-II VAD mode are obviously different from that of the “bypass LVAD” [11]. Subsequently, Gu et al. proposed that the phase difference between BJUT-II VAD and native left ventricle significantly changes the hemodynamic states of the aorta [12]. Similarly, Zhang
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Fig. 1. Geometric model and boundary condition. (A) Schematic of BJUT-II VAD. (B) The whole geometric model of the aortic valve with BJUT-II VAD. (C, D) The geometric model of the leaflets. (E) The lumped parameter model of the cardiovascular system without BJUT-II VAD support. (F) The lumped parameter model of the cardiovascular system with BJUT-II VAD support. (G) The waveforms of the LVP and AP used in the control case. (H) The waveform of the LVP and AP used in the support case. NC, noncoronary leaflet. RC, right coronary leaflet; LC, left coronary leaflet; LVP, left ventricular pressure; AP, arterial pressure.
et al. reported that BJUT-II VAD support also affects aortic swirling flow characteristics [13] and intra-ventricular flow pattern [14]. Although the above studies demonstrated that BJUT-IIVAD support can obviously change the hemodynamic environment of the aorta and the left ventricle, and these changes were significantly different from that caused by the “bypass LVAD,” the biomechanical effect of BJUT-II VAD on the aortic valve is unclear. To clarify the biomechanical mechanism of BJUT-II VAD support on the aortic valve, a numerical study employing the “fluidstructure interaction” (FSI) approach was conducted. The realistic geometric model of BJUT-II VAD was virtually placed into the aortic geometric model. The realistic blood flow field of BJUT-II VAD was generated by the rotation of the impeller. The kinematic characteristics, principal stress distribution, blood flow pattern, and wall shear stress (WSS) distribution on the leaflets were chosen as the biomechanical indicators.
2. Methods 2.1. Description of the geometric model The geometric model (support case) consisted of two parts: aortic valve and BJUT-II VAD (Fig. 1B). The aortic valve model was constructed based on a previous study [15]. The model included four parts: the ascending aorta, the aortic sinus, three leaflets, and left ventricular outflow tract. The leaflets were located between the left ventricular outflow tract and the ascending aorta. According to the clinical data, the diameter of the ascending aorta was 20 mm. The thickness of the leaflets was 0.5 mm to reduce the computational cost. On the basis of the geometric relationship between the leaflets and the aortic sinus [16], the width of the leaflets is equal to 1/3 of the perimeter of the sinus junction. Thus, the width of the leaflets in this work was 20 mm. In this study, the three
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leaflets were named the non-coronary leaflet (NC), right coronary leaflet (RC), and left coronary leaflet (LC) (Fig. 1C). The area where the leaflets were in contact with the vessel was named the leaflet commissure (Fig. 1D). The model of BJUT-II VAD was virtually placed into the ascending aorta, including the inducer blade, the impeller, and the diffuser blade (Fig. 1B, green parts). As the housing of BJTU-II VAD is close to the wall of ascending aorta, it was ignored here. In clinical practice, the inducer blade and the diffuser blade are stationary, while the impeller rotates around this axis in a counterclockwise direction. The blood is pumped by the rotating impeller from the left ventricle to the aorta. The model comprises one inlet and one outlet, namely, the ventricular inlet and the aortic outlet. Given that this study aimed to investigate the biomechanical effects of “series LVAD” on the aortic valve, the deformation of the aortic wall was ignored here. The model (control case), including the aortic model, was established as the control group.
2.4. Discretization of the FSI model The discretization strategy in this study was the same as in our previous study. The leaflets were discretized by 10-node quadratic tetrahedral elements (C3D10). The results of the previous study revealed that 20,352 elements were sufficient to obtain accurate biomechanical states. To accurately discretize the fluid domain, the octree lattice structure, providing high-order spatial discretization for the blood domain, was employed. As the geometric size of the fluid domain was similar to that of previous studies [15, 17], the lattice size determined in the previous work was used to discretize the fluid domain (0.3 mm). The number of lattices of the control case and the support case was 0.87 and 0.63 million, respectively. 2.5. Boundary conditions The biomechanical states and hemodynamic states of the aortic valve with or without BJUT-II VAD support were investigated. The case consisting of the aortic valve and BJUT-II VAD was named the support case, while the case that only included the aortic valve was named the control case. The boundary conditions of both cases were generated from the lumped parameter model [11] (Fig. 1E and 1F). This mode includes four parts, namely, the left atrium, left ventricle, BJUT-II VAD, and systemic circulation. The left ventricular pressure (LVP) and the arterial pressure (AP) were calculated as the boundary condition. LVP was used as the pressure inlet boundary condition, and AP was employed as the outlet pressure boundary condition. For the control case, the hemodynamic states of the healthy people were reproduced, as shown in Fig. 1G. For the support case, the support level of BJUTII VAD was regulated to allow the aortic valve to open periodically (Fig. 1H), in which the rotational speed of the impeller was 60 0 0 rpm. To illustrate the turbulent flow pattern in BJUT-II VAD and in the aortic root, the wall-adapting local eddy viscosity model [15] was applied, which has been proven to be able to accurately describe the near wall behavior of fluid [28].
2.2. Lattice Boltzmann theory The details of the lattice Boltzmann (LBM) approach employed in this study have been described previously [17], and only a simple explanation is shown here. LBM is a mesoscopic method from statistical physics to simulate flow problems [18]. In this study, the Bhatnagar–Gross–Krook model was employed. The governing equation could be described as in Eq. (1):
fi (x + δt ei , t + δt ) − fi (x, t ) = −
1
τ
fi (x, t ) − fieq (x, t )
(1)
where the local equilibrium distribution function is shown as Eq. (2)
fieq = ωi ρ 1 +
u·u ei · u ( ei · u ) + − Cs2 2Cs4 2Cs2 2
(2)
In these equations, fi is the density distribution function. It indicates the fraction of the particles moving with the lattice velocity i. τ represents the relaxation time of the particles. ei denotes the discrete microscopic velocity. Cs is the speed of sound. The density ρ and velocity u are represented as Eqs. (3) and (4):
ρ=
fi
2.6. Biomechanical index The distribution of principal stress, mean stress, and radial displacement (RD) was calculated. The mean stress [15] was calculated to reflect the changes in the average level of principal stress with time, as illustrated in Eq. (7):
(3)
i
ρu =
f i ei
(4)
i
stressm =
The kinematic viscosity is expressed as
τ μ = Cs2 ( − 0.5 ) t
(5)
2.3. Finite element model of the leaflets
RDm (t ) =
To describe the biomechanical property of the leaflets, the isotropic, hyperelastic incompressible, second-order Ogden model was employed based on a previous study [17]. The constitutive equation of the leaflets is reflected by Eq. (6): N 2μi ¯ αi ¯ αi ¯ αi (λ1 + λ2 + λ3 − 3 ) 2 i=1
αi
(7)
where stressm denotes the volume average principal stress, stressi represents the stress of the ith element, and voli is the volume of the ith element. The RD [17] reflects the change in the spatial position of the valve with time, and it is expressed by Eq. (8):
In this paper, the constant kinematic viscosity was used to determine the relaxation time. Moreover, the lattice model named C3D27 (3D model with 27 directional vectors) was employed.
W =
stressi ∗ voli voli
(xm (t ) − xo )2 + (zm (t ) − zo )2
(8)
where RDm is the radial displacement of the midpoint of the free edge of the leaflets (unit mm). xm (t) and zm (t) represent the spatial coordinates of the midpoint at t time. xo and zo denote the spatial coordinates of the original point.
(6)
3. Results
where W represents the strain energy function of the leaflet. λi indicates principal strain. α i and μi denote the material parameters. According to the previous work of our group [15], α 1 = 67.74, α 2 = 27.47, μ1 = 19.58kPa, and μ2 = 260.56kPa. In addition, the density of the leaflet is 1100 kg/m3 .
In this study, three time points, namely, peak systole, peak diastole, and middle point of the rapid closing period, were chosen to extract the results. The distribution of stress, the mean stress, the radial displacement, the blood flow pattern, and the WSS distribution are illustrated in Figs. 2–5. 3
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Fig. 2. Stress distribution in the two cases.
3.1. Stress distribution of the leaflets
When the left ventricle began to relax, the mean stress increased rapidly with the increase in transvalvular pressure. Moreover, the waveforms of the three leaflets were consistent. Therefore, the biomechanical environment of the three leaflets in the control case was consistent with one another. During the rapid closing phase, an obvious concussion phenomenon in the mean stress curve of the leaflet was observed (region a). By contrast, the biomechanical environment of the leaflets in the support case was quite different from that in the control case. Fig. 3B shows the waveform of the mean stress of leaflets in the support case. Compared with that in the control case, the mean stress in the support case was obviously lower (maximum mean stress, 0.26 MPa in the control case vs. 0.03 MPa in the support case). In addition, the mean stress curves of the three leaflets were not consistent with one another. Thus, the biomechanical environment of the three leaflets in the support case was quite different from that in the control case. Moreover, no concussion phenomenon in the mean stress curve was found in the support case (region b). Fig. 3C and 3D illustrate the waveforms of RD in the two cases. In the control case, the waveforms of the RD of the three leaflets were consistent with one another (region c; Fig. 3C). The rapid valve opening time (RVOT) and rapid valve closing time (RVCT) were 100 and 50 ms, respectively. This result was in agreement with the findings reported by Kemp [19]. The obvious concussion was observed at the end of the rapid closing phase (region d). In the support case, the waveforms of the RD of the three leaflets were quite different from one another (region c; Figure D). RVOT
Fig. 2 illustrates the principal stress distribution of leaflets in the control case and the support case. During the systolic period, the principal stress distribution of the leaflet in both cases was similar to each other. At the peak systole, the aortic valve in both cases was fully opened. In both cases, the high stress regions were located at the free edge near the leaflet commissure (region a). However, during the diastolic period, the stress distribution in the support case was obviously different from that in the control case. For the control case, the aortic valve was fully closed, and the high stress region was located at the leaflet commissure and the belly area of the leaflet (regions b and c). However, for the support case, the aortic valve was not fully closed, and the stress distribution was more uniform than that in the control case. The level of the principal stress of the leaflet in the control case was obviously larger than that in the support case. The peak values of the stress in the control case and the support case were 0.5 and 0.12 MPa, respectively. 3.2. Dynamic characteristics of the leaflets The dynamic characteristics of the leaflets in the two cases were evaluated by utilizing the mean stress and radial displacement (Fig. 3). Fig. 3A shows the waveform of the mean stress in the control case. During the systolic period, the mean stress rapidly decreased with the decrease in the transvalvular pressure (0–0.3s). 4
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Fig. 3. Changes in the kinematic characteristics and biomechanical states in the two cases. (A) The waveform of the mean stress during the whole cardiac period in the control case. (B) The waveform of the mean stress under BJUT-II VAD support. (C) The waveform of the radial displacement of the leaflets without BJUT-II VAD support. (D) The waveform of the mean stress under BJUT-II VAD support.
and RVCT were about 175 ms and larger than 150 ms, respectively. Notably, during the diastolic period, significant differences were observed in the moving trajectories of the three leaflets. Moreover, the RD of the leaflets in the control case was significantly lower than that in the support case during the diastolic period. Thus, the aortic valve was not fully closed in the support case.
c). In addition, as the aortic valve could not be closed instantly, obvious reverse flow was observed (region d), which is consistent with a previous study [20]. However, in the support case, the level of retrograde blood flows was lower than that in the control case. Thus, the level of retrograde flow, which flowed into the aortic sinus (region c) and left ventricle (region d), was also lower in the support case than in the control case.
3.3. Blood flow pattern in both cases 3.4. WSS distribution Fig. 4 shows the blood velocity vector. To evaluate the difference in blood flow pattern between the two cases, the peak systole and the midpoint of the rapid closing phase were chosen to extract the blood flow velocity vector. At the peak systole, the aortic valve was fully opened in the two cases. In the control case, the high blood velocity region appeared in the middle of the ascending aorta. In addition, the vortex was observed in the aortic sinus (region a) and sinotubular junction (region b). In the support case, the value of the blood velocity through the aortic valve was lower than that in the control case (1.05 m/s in the control case vs. 0.60 m/s in the support case). Blood flow in the aortic sinus flowed into the ascending aorta (region a), and no vortex was found in the sinotubular junction (region b). At the midpoint of the rapid closing phase, the flow pattern in the two cases was quite different from each other. In the control case, obvious retrograde blood flow appeared in the ascending aorta. Obvious retrograde blood flowed into the aortic sinus, which benefitted coronary perfusion (region
Fig. 5 illustrates the WSS distribution in the two cases at three time points (peak systole, midpoint of rapid closing phase, and peak diastole). The distribution of WSS of the leaflets in the control case was different from that in the support case. At peak systole, the high WSS region in the control case was located at the free edges (region a), while the high WSS region in the support case was observed at the belly areas (region b). The value of WSS in the control case was lower than that in the support case (maximum WSS, 7.0 Pa in the control case vs. 12 Pa in the support case). At the midpoint of the closing phase, the high WSS region in the control case was located at the ventricular side of the leaflet (region c), as the high velocity retrograde blood flow flushed the leaflets. The WSS distribution of the three leaflets in the control case was consistent with one another. However, the high WSS region in the support case was located at the free edge of the leaflets and at the belly of the aortic sides of the leaflets (region c). 5
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Fig. 4. Blood velocity vector in the two cases.
Besides, the WSS distribution of the three leaflets in the support case was not consistent with one another. In addition, the level of WSS in the control case was larger than that in the support case (maximum WSS in the control case was 15 Pa vs. that in the support case was 11Pa). At peak diastole, the area of the high WSS region in the control case was larger than that in the support case (region d).
ometric model of BJUT-II VAD was virtually placed into the ascending aorta to generate a realistic hemodynamic environment. The biomechanical states of the aortic leaflets with and without BJUT-II VAD support were calculated by combining the LBM and FE method. To our knowledge, this study is the first to investigate the biomechanical effects of the novel “series LVAD” on the aortic valve. The results demonstrated that the implantation of BJUTII VAD significantly changed the hemodynamic environment of the aortic root and the biomechanical states of the aortic leaflets. Compared with the control case, BJUT-II VAD support could obviously reduce the level of stress of the leaflet. Moreover, compared with support by the traditional “bypass LVAD,” BJUT-II VAD support
4. Discussion In this study, the biomechanical effects of BJUT-II VAD on the aortic valve were investigated by using the FSI method. The ge6
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Fig. 5. Distribution of WSS in the two cases.
could maintain the aortic valve opening periodically, which may prevent valve disease. The stress load on the leaflets has been confirmed as an important reason for the remodeling of the aortic valve. For instance, Weston et al. reported that an increase in the stress of leaflets can reduce the expression of the alpha-smooth muscle actin (α -SMA) [21]. Similarly, Huang et al. found that α -SMA expressed by interstitial cells is regulated by mechanical stress [22]. Bogdanova et al. recently proposed that mechanical stress can promote the expression of osteogenic genes in interstitial cells, which might be a potential reason for aortic valve calcification [23]. In short, previous studies demonstrated that excessive stress load can promote the remodeling of the aortic leaflets. According to a previous study, the transvalvular pressure gradients of the aortic valve increase as the “bypass LVAD” support level increases [24]. The stress load of leaflets would then increase accordingly. Therefore, reducing the impact of LVAD on aortic leaflet stress level has become the direction of future research. Although our group previously demon-
strated that regulating the work mode of “bypass LVAD” can alleviate the effect of “bypass LVAD” support on the stress of the leaflets to some extent [15], the stress load of leaflet with LVAD support is still obviously higher than that in healthy condition [17]. However, the present study demonstrated that the biomechanical effects of BUJUT-II VAD on the aortic valve were quite different from that of “bypass LVAD.” The stress load on the aortic leaflets in the support case was significantly lower than that in the control case (Figs. 2, 3A, and 3B). Thus, BJUT-II VAD could not only achieve perfusion but also significantly reduce the stress load of the valve, thereby playing a good role in maintaining the biomechanical properties of the valve. Clinical studies found that “bypass LVAD” support can enlarge the diameter of the aortic root [6, 7]. Pressure in the aortic root increases with the increase in the support level of BJUT-II VAD, resulting in active root dilatation, which leads to aortic valve insufficiency. However, this complication could be effectively avoided by the series LVAD. We found that the stress load on the leaflet 7
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was reduced with the use of the BJUT-II VAD support. Given that the inlet of BJUT-II VAD is located near the aortic root, BJUT-II VAD could reduce the pressure in the aortic root. Therefore, “series LVAD” can effectively prevent aortic root dilation. According to a previous clinical study, after “bypass LVAD” implantation, the closing duration of the aortic valve increases significantly with the increase in the LVAD support level [28]. Researchers demonstrated that the failure to maintain aortic valve periodic opening induces commissural fusion of the aortic valve leaflets [25]. BJUT-II VAD could significantly change the dynamic characteristics of the leaflets during the rapid opening phase and the rapid closing phase (Fig. 3C and 3D). Compared with that in the control case, the RVOT in the support case was significantly prolonged (100 ms in the control case vs. 175 ms in the support case). BJUT-II VAD is a kind of continuous flow LVAD, so during the whole cardiac cycle, blood is continuously pumped from the left ventricle, thereby reducing the left ventricular preload. In accordance with the Frank–Starling law [26], the myocardial contractile force would decrease with the decrease in the left ventricular preload, resulting in the reduction of the LVP at the systolic phase. Similarly, the RVCT of the leaflets in the support case was obviously larger than that in the control case. The transvalvular pressure gradient of the aortic valve during the diastolic phase was obviously reduced by BJUT-II VAD support. These results demonstrated that the aortic valve could open periodically after “series LVAD” implantation, thereby reducing the risk of aortic valve disease. From the curves of the RD of the leaflets, we found significant differences in the motion trajectories of the three leaflets with the implantation of BJUT-II VAD (Fig. 3D). The rotation of the impeller of BJUT-II VAD affected the blood flow pattern around the leaflets, which in turn changed the dynamic characteristics of the three leaflets. This result was also confirmed from the distribution of WSS (Fig. 5). The distribution of WSS in the control case was consistent with each other, while obvious differences in the distribution of WSS were observed in the support case. Local blood flow pattern around the three leaflets differed. This phenomenon suggested that the influence of BJUT-II VAV on the flow pattern included not only the downstream of aorta but also the aortic root. This abnormal flow pattern may lead to the remodeling of the leaflets and the aortic wall [27]. The effects of “series LVAD” on coronary perfusion are a controversial issue. As the inlet of the “series LVAD” is close to the entrance of coronary artery, which is located in the aortic sinus, coronary perfusion may be reduced with the support of the “series LVAD.” This problem was confirmed by the results of this study. After BJUT-II VAD was implanted, the retrograde blood flow during the diastolic phase was significantly reduced (Fig. 4 region c), which then reduced the amount of coronary perfusion. However, whether this decrease in coronary perfusion would necessarily lead to insufficient blood supply to the heart is unknown. Although BJUT-II VAD support reduces the coronary perfusion, cardiac work is also significantly reduced by BJUT-II VAD support. Thus, coronary perfusion and cardiac oxygen consumption can reach a new balance. This phenomenon suggested that we need to pay attention to the regulation of the support level of “series LVAD” and choose an appropriate unloading level to prevent the excessive reduction of coronary blood flow.
the biomechanical effects of BJUT-II VAD were quite different from those resulting from traditional “bypass LVAD.” Compared with those in the control case, BJUT-II VAD support could significantly reduce the stress load of the leaflet (maximum stress, 0.5 MPa in the control case vs. 0.12 MPa in the support case). Similarly, the rapid valve opening time (100 ms in the control case vs. 175 ms in the support case) and rapid valve closing time (50 ms in the control case vs. 150 ms in the support case) in the support case were obviously longer than those in the control case. Moreover, BJUT-II VAD support reduced the retrograde blood flow during the diastolic phase and significantly changed the distribution of WSS of the leaflets. In short, while unloading the left ventricle, BJUTII VAD could provide beneficial biomechanical states for the aortic leaflets, thereby reducing the risk of aortic valve disease. Declaration of Competing Interest None. Acknowledgements including declarations Funding: This study was partly funded by the National Natural Science Foundation of China (Grant Nos. 61931013, 11832003 and 11602007), the Key Research and Development Program (2017YFC0111104), New Talent (0150 0 05141180 02) and Youth Top Talent training Program (CIT&TCD201904025). References [1] JA. Friedman, Experiences of left ventricular assist device-destination therapy recipients: a systematic review and meta-synthesis, Heart Lung (2020) S0147-9563(20)30084-4. [2] Y Vaidya, S Patibandla, AS Dhamoon, Left Ventricular Assist Devices (LVAD), StatPearls. Treasure Island (FL): StatPearls Publishing, 2020. [3] JA Maradey, MJ Singleton, TJ O’Neill, et al., Management of ventricular arrhythmias in patients with LVAD, Curr. Opin. Cardiol. 35 (3) (2020) 289-294. [4] AN Rosenbaum, AL Clavell, JM Stulak, A Behfar, Correction of high afterload improves low cardiac output in patients supported on left ventricular assist device therapy, ASAIO J. (2020) 10.1097/MAT.0 0 0 0 0 0 0 0 0 0 0 01159. [5] CB Patel, L Blue, B Cagliostro, et al., Left ventricular assist systems and infection-related outcomes: a comprehensive analysis of the MOMENTUM 3 trial, J. Heart Lung Transplant (2020) S1053-2498(20):31428-5. [6] NM Fine, SJ Park, JM Stulak, et al., Proximal thoracic aorta dimensions after continuous-flow left ventricular assist device implantation: longitudinal changes and relation to aortic valve insufficiency, J. Heart Lung Transplant 35 (4) (2016) 423-432. [7] N Bouabdallaoui, I El-Hamamsy, M Pham, et al., Aortic regurgitation in patients with a left ventricular assist device: a contemporary review, J. Heart Lung Transplant 37 (11) (2018) 1289-1297. [8] Y Chang, B. Gao, Modeling and identification of an intra-aorta pump, ASAIO J. 56 (6) (2010) 504-509. [9] Y Chang, B. Gao, A global sliding mode controller design for an intra-aorta pump, ASAIO J. 56 (6) (2010) 510-516. [10] Y Xuan, Y Chang, K Gu, B Gao, Hemodynamic simulation study of a novel intra-aorta left ventricular assist device, ASAIO J. 58 (5) (2012) 462-469. [11] B Gao, Y Chang, Y Xuan, Y Zeng, Y Liu, The hemodynamic effect of the support mode for the intra-aorta pump on the cardiovascular system, Artif. Organs 37 (2) (2013) 157-165. [12] K Gu, B Gao, Y Chang, Y Zeng, The hemodynamic effect of phase differences between the BJUT-II ventricular assist device and native heart on the cardiovascular system, Artif. Organs 38 (11) (2014) 914-923. [13] Q Zhang, B Gao, Y Chang, Effect of different rotational directions of bjut-ii vad on aortic swirling flow characteristics: a primary computational fluid dynamics study, Med. Sci. Monit. 22 (2016) 2576-2588. [14] Q Zhang, B Gao, Y Chang, Computational analysis of intra-ventricular flow pattern under partial and full support of BJUT-II VAD, Med. Sci. Monit. 23 (2017) 1043-1054. [15] B Gao, Q Zhang, Y Chang, Hemodynamic effects of support modes of LVADs on the aortic valve, Med. Biol. Eng. Comput. 57 (12) (2019) 2657-2671. [16] L De Kerchove, M Momeni, G Aphram, et al., Free margin length and coaptation surface area in normal tricuspid aortic valve: an anatomical study, Eur. J. Cardiothorac. Surg. 53 (5) (2018) 1040-1048. [17] B Gao, Q. Zhang, Biomechanical effects of the working modes of LVADs on the aortic valve: a primary numerical study, Comput. Methods Programs Biomed. 193 (2020) 105512. [18] YW Kim, JY Moon, WJ Li, et al., Effect of membrane insertion for tricuspid regurgitation using immersed-boundary lattice Boltzmann method, Comput. Methods Programs Biomed. 191 (2020) 105421.
5. Conclusion In this study, the biomechanical effects of the novel “series LVAD” (BJUT-II VAD) support on the aortic valve were investigated by the FSI approach. The geometric model of BJUT-II VAD is virtually implanted into the ascending aorta to generate the realistic flow pattern for the aortic valve. Results demonstrated that 8
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[19] I Kemp, K Dellimore, R Rodriguez, et al., Experimental validation of the fluid-structure interaction simulation of a bioprosthetic aortic heart valve, Australas Phys. Eng. Sci. Med. 36 (3) (2013) 363–373. [20] R Toninato, J Salmon, FM Susin, A Ducci, G Burriesci, Physiological vortices in the sinuses of Valsalva: an in vitro approach for bio-prosthetic valves, J. Biomech. 49 (13) (2016) 2635-2643. [21] MW Weston, AP. Yoganathan, Biosynthetic activity in heart valve leaflets in response to in vitro flow environments, Ann. Biomed. Eng. 29 (9) (2001) 752-763. [22] HY Huang, J Liao, MS Sacks, In-situ deformation of the aortic valve interstitial cell nucleus under diastolic loading, J. Biomech. Eng. 129 (2007) 880–889. [23] M Bogdanova, A Kostina, K Zihlavnikova Enayati, et al., Inflammation and mechanical stress stimulate osteogenic differentiation of human aortic valve interstitial cells, Front Physiol. 9 (2018) 1635. [24] J Holtz, J. Teuteberg, Management of aortic insufficiency in the continuous flow left ventricular assist device population, Curr. Heart Fail Rep. 11 (1) (2014) 103-110.
[25] M Hatano, K Kinugawa, T Shiga, et al., Less frequent opening of the aortic valve and a continuous flow pump are risk factors for postoperative onset of aortic insufficiency in patients with a left ventricular assist device, Circ. J. 75 (5) (2011) 1147-1155. [26] K Fukamachi, A Shiose, A Massiello, et al., Preload sensitivity in cardiac assist devices, Ann. Thorac. Surg. 95 (1) (2013) 373-380. [27] X Wang, J Lee, M Ali, J Kim, CMR Lacerda, Phenotype transformation of aortic valve interstitial cells due to applied shear stresses within a microfluidic chip, Ann. Biomed. Eng. 45 (10) (2017) 2269-2280. [28] B Gao, Q. Zhang, Biomechanical effects of the working modes of LVADs on the aortic valve: a primary numerical study, Comput. Methods Programs Biomed. 193 (2020) 105512.
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