There are several methods for treating aortic stenosis including transcatheter valve implantation (TAVI) and surgical aortic valve replacement. Among these, TAVI is highly recommended for elderly patients with high surgical risk or a life expectancy of less than 10 yr. However, recent research findings indicate that thrombosis after TAVI leads to the malfunction of TAVI leaflets, which increases the risk of stroke and heart attack. Since the mechanism of thrombus formation is unclear, this study aimed to investigate the sinus hemodynamics after TAVI in different configurations using particle image velocimetry. The results showed that compared with SAV, the TAV resulted in a relatively low velocity at the sinus owing to the native leaflet and skirt of the TAV. The native leaflet length, covering over 75% of TAV, significantly increased the flow stasis and particle residence. In addition, a larger sinus diameter corresponded to a larger stasis area of the same length as that of the native leaflet. According to this study, patients with long native leaflets in their aortic sinus are at a higher risk of developing thrombosis and may require a higher deployment during treatment.
I. INTRODUCTION
Aortic stenosis (AS) is a disease caused by narrowing the aortic valve, primarily caused by degeneration and calcification. This disease leads to the thickening and stiffening of the aortic valve, which results in an increased pressure gradient between the left ventricle and the aorta. AS can causes various symptoms, including chest pain, reduced exercise ability, and heart failure.1 Patients suffering from severe AS are advised to treat interventional or surgical replacement of the diseased aortic valve.2 This approach addresses the underlying issue by replacing the affected valve, improving blood flow, and relieving the symptoms associated with AS.
Types of prosthetic valves are available for treating AS, including a mechanical valve or a bioprosthetic valve, and options for treatment exist such as surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI). A mechanical valve is recommended over a bioprosthetic valve for patients below 50 yr of age without contraindications to anti-coagulation, whereas a bioprosthetic valve is recommended for patients above 65 yr of age, for whom anti-coagulant therapy is contraindicated.3 When considering treatment options, distinct factors come into play depending on the patient's circumstances. SAVR is typically recommended for patients with a longer life expectancy, exceeding 20 yr. This approach involves open-heart surgery, where the diseased valve is replaced with a prosthetic valve, usually made from animal tissue or a synthetic material. On the other hand, TAVI is often the preferred choice for elderly patients who have a high risk of surgical complications or a shorter life expectancy of less than 10 yr. TAVI is a minimally invasive procedure in which a new valve is implanted using a catheter. This procedure avoids the need for open-heart surgery and can be performed with reduced risks and a faster recovery time.
The development of interventional techniques and the compelling data obtained from randomized trials, PARTNER A and B, have played a significant role in establishing TAVI as an important alternative to SAVR for patients with a high surgical risk. The PARTNER A and B trials have provided valuable evidence supporting the effectiveness of TAVI.4 These trials have demonstrated favorable outcomes regarding mortality rates, functional improvement, and quality of life for AS patients with a high surgical risk. Consequently, TAVI has become an important alternative to SAVR in severe AS patients.
Recent studies have highlighted a crucial discovery in a specific subgroup of patients with a transcatheter aortic valve (TAV).5,6 These studies have found that thrombosis can result in reduce the motion of the TAV leaflets and potential complications such as stroke and heart attack.7–9 This finding suggests that it is essential to comprehend the mechanism of thrombus formation in the aortic sinus. As part of it, in-vitro experiments with post-TAVI were conducted in various configurations using particle image velocimetry (PIV). Several research groups have directed their attention toward studying the neo-sinus and aortic sinus, while other groups have shifted their focus toward investigating the downstream after TAVI. The presence of TAV develops flow stasis, which is attributed to thrombosis, in the neo-sinus and the aortic sinus.10–12 To reduce the risk of thrombosis, it has been recommended to use a small neo-sinus volume with a high implantation depth, which can help prevent stagnation.13 The present study highlights how implantation mismatches may affect the structure and intensity of the turbulent flow in the aortic root.14 Several researchers used 3D particle tracking velocimetry (PTV), and they confirmed particle movement in ascending aorta and shear stress distributions following the implantation of CoreValve and Evolut R valve.15 Another group confirmed a decrease in regurgitation after TAVI compared to regurgitation caused by severe aortic stenosis but suggested that thrombosis was still likely to occur due to high shear stress caused by systolic jets.16
A recent study reported that thrombosis not only is formed in the neo-sinus but also develops in the aortic sinus of post-TAVI patients.17 A previous study reported that TAV significantly altered the physiological sinus flow owing to an extended stagnation region at the base of the sinus,10 which provided a fluid dynamic environment, thereby promoting thrombotic phenomena and contributing to thromboembolic and ischemic events. Inspired by recent findings, we hypothesized that TAV also affects the inherent sinus flow, which could increase the risk of thrombosis in the aortic sinus. Leonardo da Vinci's representation of vortices in the aortic sinus and subsequent studies showed that the inherent vortex flow in the aortic sinus corresponds to the opening function of the heart valve and the washout of the blood flow in the aortic sinus [Fig. 1(a)].18 Implantation of the prosthetic valve while preserving the native leaflets could possibly affect the blood flow in the native sinus, particularly the vortex flow structure [Fig. 1(b)]. It is still unclear how TAV alters the sinus hemodynamics, and the size of the aortic sinus and native leaflet affects the result.
Another research has been conducted to explore post-procedural interventions or establish an environment that is resistant to thrombus development. Techniques have been explored to improve an environment prone to thrombus formation such as fracturing the native leaflet, modifying its geometry, and valve-in-valve (ViV) technique. The removal of a portion of the native leaflets has shown positive results, leading to a decrease in flow stagnation within the neo-sinus.19 For the ViV technique, self-expanding supra-annular valves demonstrate faster washouts compared to a balloon-expandable valve of equivalent size.20 For TAVI procedures or post-procedures, we investigated whether shortening the native leaflet length surrounding the TAV help to reduce the potential thrombosis inside the aortic sinus.
In this study, we aim to comprehensively investigate post-TAVI hemodynamics in the native sinus and evaluate the effects of native leaflet length, TAV size, and sinus diameter. In-vitro experiments were conducted using an aorta acrylic phantom, a cardiovascular pulsatile piston pump, and 2D PIV. The surgical aortic valve (SAV) and two TAVs of different sizes were assessed. Based on the instantaneous velocity field by PIV, we compared various hemodynamic indices, including velocity, vortex, flow stasis, and particle residence. The results demonstrated the hemodynamic difference between SAV and TAV and revealed the unfavorable flow caused by the TAV in the native sinus.
II. MATERIALS AND METHODS
A. In-vitro experimental setup
To facilitate the investigation of the fluid dynamics within the aortic sinus, optical access was required for the PIV experiment. A transparent acrylic aortic phantom was fabricated using a five-axis CNC machine (SIRIUS-UL+, HWACHEON, Seoul, Korea). The rigid model was designed to resemble an idealized shape of the aortic sinus. Three different models, with sinus diameters ranging from 35 to 45 mm, were utilized to assess the influence of sinus diameter on fluid dynamics. The annulus and sinotubular junction (STJ) diameters were set at 30 and 27 mm, respectively (Figs. S1 and S2 in the supplementary material). The aortic phantom design was validated by two coauthors of this study, radiologists of the Asan Medical Center.
To investigate the impact of valve type and size on sinus hemodynamics, three bioprosthetic valves were employed in our study. As a control, we utilized the INTUITY Elite (Edward Lifesciences, California, USA), which is a SAV with a stent diameter of 19 mm (referred to as SAV 19 mm). Additionally, two TAVs, namely, the SAPIEN3 (Edward Lifesciences, California, USA), were included in the investigation. These TAVs had diameters of 23 (TAV 23 mm) and 26 mm (TAV 26 mm). The selection of the bioprosthetic valves was based on the recommended annulus sizes for each valve with the SAV 19 mm, TAV 23 mm, and TAV 26 mm corresponding to annulus sizes of 19.8, 18–22, and 21–25 mm, respectively.21,22 The SAV 19 mm and TAV 23 mm were selected for use in comparable patient groups, as they were suitable for individuals with similar annulus diameters. On the other hand, the TAV 26 mm was specifically chosen for patients with larger annulus diameters that exceed the dimensions accommodated by both the SAV 19 mm and TAV 23 mm.
In this study, the native leaflet length and deployment depth were determined based on the specifications of the TAVs used. To examine their impact on sinus hemodynamics, native leaflet lengths representing 0%, 25%, 50%, 75%, and 100% of the TAV height were employed. For the TAV 23 mm, the native leaflet lengths were set at 1.8, 5.4, 9.0, 12.6, and 16.2 mm. For TAV 26 mm, the corresponding lengths were 2.0, 6.0, 10.0, 14.0, and 18.0 mm. The native leaflets surrounding the TAVs were fabricated using a 3D printer (Prusa Research, Praha, Czech Republic) with an inner diameter designed to match the stent diameter of the TAVs and a thickness of 1.5 mm (Fig. 2). The native leaflets were cylindrical in shape based on the ideal shape provided by Midha et al.11 The deployment depths for the SAV 19 mm, TAV 23 mm, and TAV 26 mm were set at 0, 1.8, and 2.0 mm, respectively. According to Yasser et al., these deployment depths for each valve corresponded to a “high” position.23 Three deployment depths (zero, convention, and low) were also assessed under medium sinus diameter and 50% of native leaflet length (Fig. S2 in the supplementary material).
Schematic representation of native leaflet with surgical aortic valve (SAV) and transcatheter aortic valves (TAVs).
Schematic representation of native leaflet with surgical aortic valve (SAV) and transcatheter aortic valves (TAVs).
We evaluated an in-vitro experiment with a cardiovascular pulsatile piston pump under physiological conditions. This system simulated the hemodynamic conditions by utilizing a pulsatile piston pump to reproduce the flow rate and a transducer to measure the pressure (Fig. 3). The in-house pulsatile piston pump had been previously calibrated and was able to mimic the physiological heart-stroke volume.24 The experimental conditions were configured as follows: a heart rate of 60 beats per minute, a cardiac output of 4.8 l/min, and a maximum flow rate of 20 l/min. Pressure measurement was taken at the pre- and post-valvular positions with the average post-valvular pressure set at 100 mm Hg.
Schematic representation of (a) in-vitro experiment with a simulated heart piston pump, (b) flow rate of a piston pump, and (c) a particle image velocimetry (PIV) setup.
Schematic representation of (a) in-vitro experiment with a simulated heart piston pump, (b) flow rate of a piston pump, and (c) a particle image velocimetry (PIV) setup.
B. Particle image velocimetry (PIV)
The implementation of 2D PIV, a non-intrusive technique for flow visualization, required specific optical equipment. A 10 W continuous 532 nm Nd:YAG laser (MGL-W-532, CNI, Changchun, China) illuminated the seeding particles, which was polymetric hollow glass sphere (Dantec dynamics, Skovlunde, Denmark) with an average diameter of 10 μm and a density of 1090 kg/m3. To shape the laser sheet to a thickness of approximately 2 mm, a cylindrical and spherical optical lens with a focal length of 1000 mm was employed. The illuminated plane was adjusted to the center of the bioprosthetic valves (Fig. 3). A high-speed camera (Phantom VEO 710L, Vision Research, New Jersey, USA) equipped with a macro lens (VR Micro-NIKKOR 105 mm, Nikon, Tokyo, Japan). The camera captured images at a resolution of 1280 × 720 pixels and a frame rate of 300 fps. Furthermore, the burst mode of the camera was used to capture both high-velocity jet flow and low-velocity sinus flow (Fig. S4 in the supplementary material). The burst periods for SAV 19 mm, TAV 23 mm, and TAV 26 mm were set at 150, 150, and 200 μs, respectively. To replicate the fluid properties of blood, a working fluid with a viscosity of 3.4 cP and a density of 1100 kg/m3 was prepared by mixing glycerin and saline in a mass ratio of 40:60.
To enhance the contrast and reduce background noise and reflections around the valve stent and wall of the aortic sinus model, the particle images were subtracted from the average particle image. The resulting preprocessed images were then imported into PIVlab, which is an open-source program based on MATLAB (MathWorks, California, USA).25 In this study, a cross correlation technique with fast-Fourier transformation (FFT) was applied, and an interrogation window ranging from 64 × 64 pixels to 32 × 32 pixels, with a 50% window overlapping, was used. Subpixel correction was achieved by employing a 2 × 3 Gaussian fitting method. Therefore, the final resolution of the velocity field was 16 × 16 pixels, corresponding to an area of 0.98 × 0.98 mm2. To further refine the data, a smoothing filter is based on penalized least squares regression using the discrete cosine transform (DCT-PLS). An ensemble average was performed for a total of 98 cycles of measurements to reduce measurement noise and ensure the validation (Fig. 4).
C. Data analysis
We employed stasis, vortex, and particle residence to study the hemodynamics of the aortic sinus as hemodynamic parameters. By incorporating velocity field analysis, the vortex parameter was employed to examine the flow structure within the aortic sinus, discerning counterclockwise, clockwise, or bidirectional patterns. Moreover, the stasis and particle residence parameters were considered in relation to the risk of thrombosis, specifically associated with flow stagnation.
The particle residence as sinus hemodynamics parameters helped to understand the movement of particles within the aortic sinus. It quantified the number of particles that remained within the aortic sinus, expressed as a ratio relative to the total number of particles initially present, Similar to stasis, particle residence was also linked to the risk of thrombosis arising from flow stagnation. To determine the particle residence, numerical integration of the velocity field was necessary.
III. RESULTS
A. Hemodynamic characteristics of SAV and TAV
To compare velocity and hemodynamic parameters, we carefully selected representative cases with a medium sinus diameter and a native leaflet length of 75%, which closely resembled the clinical approach of TAVI. A control group consisting of a SAV 19 mm was also included for comparison. Figure 5 provides a visual representation of the velocity fields over time for SAV 19 mm, TAV 23 mm, and TAV 26 mm, revealing distinct peak velocities and flow patterns.
Velocity contour over time of SAV 19 mm, TAV 23 mm, TAV 26 mm with medium sinus diameter and a native leaflet length of 75%.
Velocity contour over time of SAV 19 mm, TAV 23 mm, TAV 26 mm with medium sinus diameter and a native leaflet length of 75%.
SAV 19 mm exhibited a relatively narrow velocity profile with higher velocity magnitude compared to the TAVs. The recorded peak velocities for SAV 19 mm, TAV 23 mm, and TAV 26 mm were 2.4, 1.7, and 1.4 m/s, respectively. During early systole, a recirculation region formed around the systolic jet and moved along its direction. However, TAV 26 mm displayed a small gap between the jet and the aorta, resulting in the absence of recirculation. Moreover, the velocity profiles during peak systole varied for each valve, showing differences on the left and right sides based on the systolic jet. On the left side, the velocity direction retrograded compared to the main jet and had a lower magnitude. Simultaneously, the velocity profile on the right side exhibited distinct characteristics for each valve. In the case of SAV 19 mm, the velocity propagated toward the aorta, eliminating the presence of a low-velocity region on the right side. TAV 23 mm displayed a similar flow pattern on the left side, with a retrograded direction and non-propagation of the main jet, but this was not observed in TAV 26 mm. During late systole, as the valve began to close, a momentary backflow occurred, leading to an increase in velocity as flow from the aorta was drawn into the valve. Flow entered the aortic sinus, influencing the flow structure. Vortical structures were observed in each valve during diastole. SAV 19 mm exhibited a counterclockwise rotation structure that persisted. In the case of TAV 23 mm, we observed the coexistence of counterclockwise and clockwise vortical structures due to changes in the inflow direction caused by the native leaflet. However, confirming this structure in TAV 26 mm posed challenges. Further details regarding the vortical structure are depicted using vortex identification in Fig. 6 (Multimedia view).
Comparison of hemodynamic parameters for SAV 19 mm, TAV 23 mm, and TAV 26 mm with medium sinus diameter with a native leaflet length of 75%. (a) Stasis, vortex at late diastole, and remaining particles at the end of one cycle and (b) particle residence (%) during four cardiac cycles. Multimedia available online.
Comparison of hemodynamic parameters for SAV 19 mm, TAV 23 mm, and TAV 26 mm with medium sinus diameter with a native leaflet length of 75%. (a) Stasis, vortex at late diastole, and remaining particles at the end of one cycle and (b) particle residence (%) during four cardiac cycles. Multimedia available online.
We comprehensively analyzed and compared hemodynamic parameters among different valves to gain insight into their performance [Fig. 6(a)]. As mentioned, while explaining the velocity field over time in Fig. 5, it was confirmed that SAV 19 mm showed a higher peak velocity than TAVs, and a narrow velocity profile was also shown accordingly.
The stasis parameter differed according to the valve type, and SAV 19 mm had lower stasis within the aortic sinus than TAVs. SAV 19 mm demonstrated high-velocity regions, from the valve stent tip to STJ, the upper part of the aortic sinus. In addition, SAV 19 mm had a maximum velocity of more than 0.05 m/s overall, and in particular, a maximum velocity of more than 0.1 m/s was distributed around the SAV. In contrast, the stasis of TAVs showed that a maximum velocity under 0.05 m/s was mainly distributed in the lower part based on the native leaflet, and a maximum velocity of about 0.1 m/s was distributed in the upper part.
We employed a technique called vortex identification to investigate the vortical structure in the aortic sinus. This method helps us to understand the rotational patterns within the flow. Our analysis observed that counterclockwise rotation is referred to as a positive vortex, while clockwise rotation is considered a negative vortex. These findings revealed distinct vortical structures for different valves. Specifically, in the case of the SAV 19 mm, a positive vortex distribution was observed from the STJ to the annulus, indicating a counterclockwise rotational flow in that region. Additionally, a negative vortex was detected near the SAV. On the other hand, the TAV 23 mm and TAV 26 mm exhibited similar vortical structures. These valves displayed positive and negative vortices, which were present based on the native leaflet of the valve.
We also conducted particle residence analysis to assess the behavior of particles within the aortic sinus. It was observed that most particles were effectively removed in the case of the SAV 19 mm. In contrast, particles tended to agglomerate in TAVs, particularly in the lower part of the native leaflet. After one cycle, the SAV 19 mm had fewer remaining particles than TAVs. Furthermore, after two cycles, all particles had exited the region of interest in the SAV 19 mm, while some remained in TAVs. Multimedia view provides visual demonstration of particle movement during four cardiac cycles. Hemodynamic parameters are provided in Tables S4–S6 in the supplementary material.
B. Effect of the native leaflet length and sinus diameter
The peak velocity was not affected by the native leaflet length and sinus diameter. However, variations in the peak velocity were observed based on different valve sizes, specifically TAV 23 mm and TAV 26 mm [Fig. 7 (Multimedia view) and Figs. S4 and S5 in the supplementary material]. The peak velocity for TAV 23 mm was 1.7 m/s, whereas for TAV 26 mm, it was 1.4 m/s. Hemodynamic parameters are provided in Tables S4–S6 in the supplementary material.
Comparison of hemodynamic parameters in the native leaflet length with medium sinus diameter. Stasis, vortex at late diastole, and remaining particles at the end of one cycle in (a) TAV 23 mm and (b) TAV 26 mm. Multimedia available online.
Comparison of hemodynamic parameters in the native leaflet length with medium sinus diameter. Stasis, vortex at late diastole, and remaining particles at the end of one cycle in (a) TAV 23 mm and (b) TAV 26 mm. Multimedia available online.
Hemodynamic parameters, including stasis, vortex, and particle residence, were influenced by the sinus diameter with noticeable differences based on the native leaflet length. These parameters were categorized into two groups: the first group comprised native leaflet lengths of 0%, 25%, and 50%, while the second group included lengths of 75% and 100%.
At a second group, the aortic sinus exhibited the highest level of stasis compared to other lengths. Conversely, the first group was associated with a concentrated region of higher velocities (0.05 m/s or more) inside the aortic sinus. These findings were consistent for both TAV 23 mm and TAV 26 mm. Moreover, while the stasis varied depending on the size of the sinus diameter, a similarity was observed among native leaflet lengths of 0%–50%, as well as a consistent worsening trend of stasis for lengths of 75%–100%. Figures S4 and S5 in the supplementary material provide visual representations of these findings.
During diastole, vortex identification was performed to analyze the vortical structures present. Interestingly, regardless of the valve size, both anti-clockwise and clockwise rotations were observed in the vortical patterns. However, as the native leaflet length increased, distinct differences in the vortical structures emerged. For native leaflet lengths below 50%, the negative vortex tended to form predominantly near the valve, while the positive vortex occupied a significant portion of the interior of the aortic sinus. In contrast, as the native leaflet length exceeded 75%, the negative vortex expanded its area while the positive vortex decreased in size. Importantly, these observations were consistent regardless of the valve size, indicating that the specific dimensions of the valve did not influence the impact of native leaflet length on vortical structures.
Particle residence measurements, although providing a snapshot after a cycle's completion, have limitations in fully understanding particle behavior. Notably, for native leaflet lengths of 0%–50%, particles were observed to disperse widely or be eliminated within the system. However, for native leaflet lengths of 75%–100%, many particles remained within the region of interest, forming clusters near the native leaflet. Detailed particle residence for four cardiac cycles can be found in Multimedia view.
Figure 8 illustrates the results for native leaflet lengths of 50%, 75%, and 100% with both TAV 23 mm and TAV 26 mm. For a native leaflet length of 50%, there was a slight disparity between TAV 23 mm and TAV 26 mm, as the percentage of particles remaining approached zero after approximately four cardiac cycles. However, this pattern did not persist for native leaflet lengths of 75% and 100%. For a native leaflet length of 75% with medium and large sinus diameters, around 10% of particles persisted over the four cardiac cycles. Specifically, for a native leaflet length of 100%, approximately 20% of particles remained. These findings indicate that the particle residence is influenced by both the native leaflet length and the sinus diameter. Furthermore, in the case of small sinus diameters, a substantial percentage of particles persisted even after four cardiac cycles, with 40% for TAV 23 mm and 20% for TAV 26 mm. In contrast, most particles (76% for TAV 23 mm and 98% for TAV 26 mm) remained within the region of interest.
Percentage of particle residence for native leaflet lengths 50%, 75%, and 100% of TAV 23 mm and TAV 26 mm.
Percentage of particle residence for native leaflet lengths 50%, 75%, and 100% of TAV 23 mm and TAV 26 mm.
Figure 9 provides a quantitative analysis of hemodynamic parameters, facilitating easy comparison between different conditions. The results highlight the influence of native leaflet length on decay and stasis (%). For native leaflet lengths ranging from 0% to 50%, the decay parameter exhibits minimal variation. However, beyond 75%, the decay parameter significantly decreases, reaching its lowest value at 100%. In contrast, the stasis (%) parameter shows a slight difference within the 0%–50% range but gradually increases from 50% to 100%, reaching its maximum value at 100%. Additionally, the absolute stasis area increases with increasing sinus diameter. Correlation analysis demonstrates a significant relationship between decay and stasis (%). The p-values calculated using TAV 23 mm and TAV 26 mm data (excluding SAV 19 mm) for decay, stasis (%), and stasis area (mm2) reveal significant differences. Specifically, the analysis confirms significant differences in decay and stasis (%) parameters among the 50%–75%, 50%–100%, and 75%–100% native leaflet length groups. Similarly, the stasis area (mm2) parameter shows significance among the small-medium, small-large, and medium-large sinus diameter groups. Any p-values equal to or below 0.05 are denoted with an asterisk (*).
Hemodynamics parameters for the experimental configurations: (a) decay, (b) stasis (%), (c) stasis (mm2), and (d) correlation between decay and stasis (%). *P < 0.05.
Hemodynamics parameters for the experimental configurations: (a) decay, (b) stasis (%), (c) stasis (mm2), and (d) correlation between decay and stasis (%). *P < 0.05.
IV. DISCUSSION
This study focused on investigating post-TAVI hemodynamics in the aortic sinus and assessing the influence of several factors, including the native leaflet length, TAV size, and sinus diameter, on sinus flow. The key findings of this study are as follows: (1) the native leaflet length covering over 75% of the TAV increased the flow stasis and particle residence in the aortic sinus, (2) a larger sinus diameter corresponded to a larger stasis area at the same native leaflet length, and (3) the decay parameter was well correlated with the velocity-based flow stasis.
The native leaflet length, particularly when covering over 75% of the TAV area, exhibited a significant impact on flow stasis and particle residence in the aortic sinus. Flow stagnation increased noticeably when the native leaflets covered a larger portion of the TAV. This phenomenon arises due to the interaction between blood flow in the aortic sinus during diastole and the native leaflet, which redirects the flow. Hemodynamic parameters associated with the SAV 19 mm showed a reduced potential for thrombosis due to lower stasis and increased decay, while TAVs were found to have a higher potential for thrombosis. The hindered exchange between the neo-sinus formed by the prosthetic valve and the native aortic sinus, along with the development of a bidirectional vortical structure, contributes to flow stagnation and challenges the removal of suspended components in the blood. These findings suggest that an increased length of the native leaflet may lead to flow stagnation and an elevated risk of thrombosis.
This study revealed the impact of aortic sinus diameter on the risk of flow stagnation. A larger aortic sinus diameter expands the stationary area despite the constant length of the native leaflet. In contrast, a smaller aortic sinus diameter increases the risk of thrombosis compared to the overall aortic sinus area. Therefore, individuals with a larger aortic sinus may face an increased risk of blood flow stagnation and potential thrombosis. It is important to note that a comprehensive assessment of thrombosis risk should consider other relevant parameters in conjunction with the size of the aortic sinus.
This study also elucidates an established correlation between the decay and stasis, underscoring their relevance in assessing potential thrombotic events within the aortic sinus. These parameters, although derived from velocity data, capture distinct aspects of the flow dynamics. Stasis parameter quantifies regions of potential stagnation within the aortic sinus, while particle residence parameter provides insight into the washout efficacy during the cardiac cycle. Therefore, considering both parameters is essential to comprehensively analyze the underlying mechanism of thrombus formation within the aortic sinus. By incorporating a multi-parameter approach, future investigations can enhance our understanding of the pathophysiology of thrombosis in the aortic sinus and facilitate the development of targeted preventive measures and treatment strategies.
Additionally, the study examined the impact of TAV skirts on sinus flow. Skirts are components of TAVs designed to prevent leakage between the TAV and the native leaflet. Although this study focused on analyzing thrombus formation factors based on native leaflet length and sinus diameter, no significant differences were observed within the natural delivery length range of 0%–50%. This finding suggests that whether the native leaflet covers the TAV skirt plays a role in the alteration of flow patterns and exacerbation of stasis and particle residence. While the presence of the native leaflet does not affect the flow pattern involving the TAV skirt, it is believed to intensify flow stagnation and particle retention. The flow into the aortic sinus forms an overall rotational structure along the valve in the case of the non-skirted SAV 19 mm. However, TAVs with sizes of 23 and 26 mm may face challenges in establishing a vortical structure to flush the interior of the aortic sinus since the flow into the neo-sinus cannot transfer to the native aortic sinus. These understandings contribute to our understanding of post-TAVI sinus flows, particularly in prolonged native shear, and can guide advancements in TAV design to mitigate the risk of thrombosis and associated complications.
Furthermore, this study provides valuable insight into the role of TAV skirts in influencing sinus flow dynamics. By analyzing thrombus formation factors based on the native leaflet length and sinus diameter, it was observed that the presence of the native leaflet covering the TAV skirt has a significant impact on flow patterns, stasis, and particle residence. In the case of SAV 19 mm, which lacks a skirt, the flow into the aortic sinus forms an overall rotational structure along the valve, minimizing the risk of flow stagnation and thrombus formation. However, TAVs with sizes of 23 and 26 mm face challenges in establishing a vortical structure to effectively flush the interior of the aortic sinus. This is because the flow into the neo-sinus cannot easily transfer to the native aortic sinus due to the presence of the native leaflet covering the TAV skirt.
Understanding the role of skirts in TAVs is crucial for designing improved prosthetic valves that minimize the risk of thrombosis and associated complications. Future advancements in TAV design should consider optimizing the skirt design to promote better flow patterns and reduce stasis within the aortic sinus. By facilitating a more efficient exchange of blood between the neo-sinus and the native aortic sinus, the risk of thrombus formation can be mitigated.
It is important to note that this study provides insight specific to post-TAVI hemodynamics in the aortic sinus and the factors influencing flow stagnation and thrombus formation. Further research is needed to validate these findings and explore additional factors that may contribute to thrombotic events following TAVI. Additionally, clinical studies and long-term follow-up are necessary to assess the clinical implications of these hemodynamic findings and guide patient management strategies.
It is essential to acknowledge the study's limitations. Some of the cases examined may need to accurately represent real-world clinical scenarios, limiting the generalizability of the findings. The in-vitro experiments utilized an idealized aortic sinus phantom, which did not account for the distensibility of the aorta, coronary flow, or patient-specific vascular geometry. The influence of coronary flow on sinus hemodynamics, which supplies approximately 5% of cardiac output during the diastolic period and affects the sinus flow pattern, was not considered.30,31 Additionally, the study employed two-dimensional flow measurements through PIV, which may need to capture the effects of three-dimensional flow structures fully. Finally, the study focused on flow stagnation and did not explore other potential contributors to thrombosis such as platelet activation or red blood cell rupture caused by turbulence.14,32 Future studies could incorporate patient-specific flexible aortic phantoms that incorporate coronary circulation and leverage advancements in 3D printing technology to replicate the complex flow dynamics within the aortic sinus more accurately.12
V. CONCLUSION
In conclusion, this study aimed to investigate the fluid dynamics within the aortic sinus using an in-vitro experimental setup. The experiment utilized a transparent acrylic aortic phantom and three different models with varying sinus diameters to assess the influence of sinus diameter on fluid dynamics. Three bioprosthetic valves, including a SAV and two TAVs, were employed to examine the impact of valve type and size on sinus hemodynamics. Native leaflet lengths and deployment depths were determined based on the specifications of the TAVs used. This study highlights the significance of the native leaflet length, the sinus diameter, and the presence of TAV skirts in influencing post-TAVI sinus flow dynamics. The findings emphasize the increased risk of flow stagnation and thrombus formation associated with longer native leaflets, smaller sinus diameters, and the presence of TAV skirts. These understandings can contribute to the development of improved TAV designs and clinical strategies aimed at reducing thrombotic complications following TAVI procedures.
SUPPLEMENTARY MATERIAL
See the supplementary material for detailed specifications of the bioprosthetic valves utilized in this study along with the recommended dimensions of the patient's annulus size for the application of these valves. Moreover, we have described the modeling and dimensions of the aortic sinus phantom. The differences in sinus hemodynamic parameters based on small and large sinus diameters, which were not elaborated in the main text, are presented. We present all hemodynamic parameters in tables for clear comparison. We have also summarized and presented the figures and results according to the deployment depth.
ACKNOWLEDGMENTS
This study was supported by the National Research Foundation of Korea (NRF – 2020R1A2C2003843, 2021R1I1A3040346), the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2022R1A5A1022977, RS-2023-00218630), and Regional Innovation Strategy (RIS) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (MOE) (2022RIS-005).
AUTHOR DECLARATIONS
Conflict of Interest
The authors have no conflicts to disclose.
Author Contributions
Dong Hyun Yang and Hojin Ha contributed equally to this paper.
Jihun Kang: Data curation (equal); Investigation (equal); Writing – original draft (equal). Hyun Jung Koo: Data curation (equal); Investigation (equal). Dong Hyun Yang: Funding acquisition (equal); Project administration (equal); Supervision (equal). Hojin Ha: Funding acquisition (equal); Project administration (equal); Supervision (equal).
DATA AVAILABILITY
The data that support the findings of this study are available from the corresponding author upon reasonable request.