Patient-tailored computational fluid dynamics models for assessing the effect of transcatheter edge-to-edge repair devices on mitral regurgitation flow convergence

Introduction

Blood flow convergence is one of the most commonly used methods for quantitatively assessing the degree of mitral regurgitation (MR). This method assumes that the shape of proximal isovelocity surface area (PISA) is hemispherical and calculates the area of the isovelocity surface near the regurgitant orifice to determine the effective regurgitant orifice area (EROA) (1,2). However, after transcatheter edge-to-edge repair (TEER), due to the TEER device altering the spatial anatomy near the orifice of MR and blocking blood flow in certain directions, the spatial shape of PISA changes. This leads to the possibility of significant errors in the calculation of the EROA via the PISA method.

In this study, computational fluid dynamics (CFD) modeling was used to examine the factors influencing the measurement of EROA via the PISA method after TEER treatment. The aim of this study was to develop solutions to reduce or eliminate these influencing factors, thereby providing a more reliable imaging basis for accurately assessing the degree of MR and prognostic analysis after TEER.

Methods

Study inclusion and criteria

This study examined three-dimensional transesophageal echocardiography (3D TEE) and contrast-enhanced cardiac computed tomography (CT) images of patients who underwent TEER treatment between January 1, 2020, and August 30, 2023, in Renmin Hospital of Wuhan University. The Ethics Committee at Renmin Hospital of Wuhan University approved the study protocol (Approval No. WDRY2021-K186). For the retrospective analysis of imaging and clinical data, the requirement of individual consent was waived by the Ethics Committee, as the study involved noninvasive computational modeling based on routinely acquired clinical imaging data. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Patients with severe degenerative mitral regurgitation (DMR) or functional mitral regurgitation (FMR) who received mitral valve TEER treatment under the guidance of 3D TEE and who had mild-or-greater MR immediately after device deployment were included. Meanwhile, the patients with poor-quality TEE images and those with misaligned CT images were excluded.

Image acquisition

All patients received contrast-enhanced cardiac CT scans within a week before their TEER procedure with a 64-slice multidetector CT system (LightSpeed VCT, GE HealthCare, Chicago, IL, USA) at a slice thickness of 0.625 mm. TEE images were captured via the EPIC 7C ultrasound diagnostic system (Philips Healthcare, Amsterdam, the Netherlands) and the X8-2T TEE probe (frequency 2–8 MHz; Philips Healthcare).

The TEE probe was inserted into the patient under general anesthesia. Implantation of the TEER device through the femoral vein was guided by TEE and cardiac angiography. TEER devices of multiple suppliers were implanted, including MitraCli G3 (Abbott Laboratories, Chicago, IL, USA), DragonFly (Dejinyouli Medical Technology Co., Hangzhou, China), and SQ-Kyrin-M (Shenqi Medical Technology Co., Ltd., Shanghai, China). Immediately after device deployment, the degree of residual MR was assessed by TEE.

Both 2D and 3D images of the mitral valve were captured. For 2D TEE, the mitral valve commissure view was captured at a 50–70° angle, and the left ventricular long-axis view was obtained at 130–150°. The 3D TEE images of mitral leaflets were captured with a 3D-zoom method with frame rate of 9–22 frames per second. Each 3D TEE image included the complete mitral valve annulus with the aortic valve positioned at the 12 o’clock position, and the depth of sampling frame was sufficient to encompass the valve leaflets and the TEER devices. All 2D and 3D images were captured in both grayscale and color Doppler flow imaging (CDFI). During the capturing of PISA images, the baseline of CDFI was shifted toward the left atrium, with an aliasing velocity (Valis) of 38.5 cm/s. Each image was captured for more than three cardiac cycles.

Since each implanted TEER device could significantly affect the PISA, images after the deployment of each device were exported separately as individual study models. If the regurgitation was less than mild after the final TEER device deployment, the images after deployment of the device were not included. All images were stored in raw Digital Imaging and Communications in Medicine (DICOM) format.

Multimodal fusion and image postprocessing

The TEE images were imported into QLAB 13.0 (Philips Healthcare) in DICOM format, where they were opened via 3DQ. These images were then exported as Cartesian DICOM files. A specific frame, clearly showing the valve and TEER device during the mid contraction, was imported into Mimics 19.0 software (Materialise, Leuven, Belgium) for model reconstruction of the mitral leaflets and the TEER devices. Different grayscale threshold ranges were applied sequentially to segment the mitral leaflets (around a grayscale value of 60) and the TEER devices (around a grayscale value of 110) to create volumetric masks for each. These masks were then smoothed and used to generate components. Anatomical structures of the mitral leaflets on the left atrial side were segmented through use of the annotation tools. Based on this information, spatial models of the mitral leaflet were reconstructed. Cutting and smoothing tools were also used to precisely segment the in vivo structural model of the TEER device.

Postprocessing of contrast-enhanced cardiac CT images was also performed with Mimics 19.0. The automatic heart segmentation function was used to segment the left atrium and left ventricle. An interactive moving tool was used to position the mitral valve orifice at the coordinate origin, with the long axis of the left ventricle being aligned to be parallel to the y-axis. The 3D TEE-segmented models of the mitral leaflets and TEER devices were aligned with the left atrium-left ventricle model based on cardiac CT. This precise alignment was based on the anatomical landmarks of the left ventricular outflow tract, aortic annulus, and mitral annulus. Structural details of the mitral valve regurgitation orifice, including vena contracta (VC) and 3D vena contracta area (3DVCA), were added based on the TEE information. Models of mitral leaflets, TEER devices, and the left atrium and left ventricle were exported in STL format (Figure 1).

Figure 1 The method for establishing an individualized fusion imaging CFD model. In both 3D TEE and cardiac CT, threshold-based segmentation was applied to reconstruct models of the MV (A-C), TEER device (D-F), and LA and LV (G-I). Each part of the model underwent postprocessing and multimodal matching fusion (J). Subsequently, the model parts underwent meshing (K), and the definition of computer-simulated flow fields (L) was defined to produce a personalized mitral regurgitation model after TEER surgery (M). 3D TEE, three-dimensional transesophageal echocardiography; CFD, computational fluid dynamics; CT, computed tomography; LA, left atrium; LV, left ventricle; MV, mitral valve; TEER, transcatheter edge-to-edge repair.

Construction and measurement analysis of CFD models

For the construction and simulation of the CFD model, Ansys Workbench (Ansys, Canonsburg, PA, USA) was employed. The shear stress transport transition model was employed for CFD simulations. The effect of ventricular contraction was mimicked by applying a time-varying pressure boundary condition at the endocardial surface of the left ventricle. The absolute pressure was determined by adding the dynamic pressure difference of the systolic mitral valve regurgitation measured by continuous wave Doppler to the pressure in the left atrium. The pressure at the distal end of the left ventricular outflow tract was calculated based on the transaortic valve pressure difference measured by continuous wave Doppler at the aortic orifice. The pressure in the pulmonary veins was approximated to be equal to the pressure in the left atrium as determined through catheter-based measurements.

The mitral valve leaflets, TEER device, and left atrial wall were defined as the nonsliding stationary wall. The internal flow field was filled with fluid with density of 1,050 kg/m³. To simulate blood viscosity at body temperature, the dynamic viscosity was calculated with the power law for non-Newtonian fluids as follows: μ=K×(γ˙)(n=1), where K=0.017 kg·sⁿ⁻²·m⁻¹ is the consistency index, n=0.708 is the power law index, and γ˙ is the shear rate (3-5). A transient flow field CFD model was used to simulate mitral valve regurgitation, with a time step set to 0.01 seconds.

After the CFD simulation calculations were completed, the results were transferred to the CFD post module of Ansys Workbench for PISA measurement. The y-axis component of velocity was used to simulate the angle-dependent echocardiographic color Doppler signal, with the velocity signal color-coded in similar fashion to that of TEE images, and the Valis was set at 38.5 cm/s. To ensure the accuracy of the CFD simulation, the PISA of each CFD model was compared with the corresponding 3D TEE-color Doppler flow image to ensure consistency in spatial form and measurements (Figure 2).

Figure 2 CFD models with and without the TEER device compared with the corresponding TEE images. The CFD models (A,D) were cross-referenced with TEE-color Doppler flow image (B,E) for precision validation. Subsequently, the TEER device was removed from the geometric model of CFD (C,F) to determine the effect of the TEER device on the blood flow convergence of mitral regurgitation. CDFI, color Doppler flow imaging; CFD, computational fluid dynamics; TEE, transesophageal echocardiography; TEER, transcatheter edge-to-edge repair.

PISA measurements were obtained on a plane perpendicular to the mitral annulus and passing through the center of the regurgitation orifice. The PISA radius (R1) on this plane and the maximum flow speed (Vmax) were used to calculate the EROA with the following formula: EROA with TEER device (EORA1) = (2πR1² × Valis)/Vmax. Additionally, the vertical distance D from the midpoint of VC to the TEER device was also measured.

The TEER device was then removed from the CFD model, allowing the fluid part to cover this area, with all other hemodynamic parameters (ventricular geometry, pressure gradients, and orifice shape) being kept constant. This setup was used to repeat the CFD calculations. Measurements were obtained in the plane for the PISA radius, R2, which accounted for the absence of the TEER device’s influence. The EROA2 was calculated using the following formula: EROA2 = (2πR2² × Valis)/Vmax. The ratio of EROA2 to EROA1 was then used as a correction coefficient (CC) for adjustment of the PISA method calculations for the impact of the TEER device.

Statistical analysis

Continuous data are presented as the mean ± standard deviation (SD), while categorical data are presented as percentages or frequencies. The paired t-test was employed to assess differences between measurement methods, and linear regression models were used to examine relationships between parameters. RStudio (Posit, Boston, MA, USA) and MedCalc 11.4 (MedCalc Software, Ostend, Belgium) were employed for statistical analyses. A two-tailed P value of <0.05 was considered statistically significant.

Results

The spatial relationship between PISA and the TEER device

3D TEE images showing mild-or-greater residual mitral valve regurgitation after TEER device release were collected from 38 patients (23 with FMR and 15 with DMR; 21 males and 17 females; average age 67.82±9.05 years). In 11 of these patients, mild-or-greater regurgitation persisted after the implantation of a second TEER device. A total of 49 3D TEE images of post-TEER residual regurgitation were collected (38 images with one TEER device and 11 images with two TEER devices). Among all images, 41 displayed 1 PISA, and 8 showed 2 PISAs, totaling 57 observed PISAs of MR. The Bland-Altman limits of agreement for the CFD PISA radius and TEE PISA radius with TEER devices with a Valis of 38.5 cm/s were 0.003±0.039 cm.

All PISAs were categorized into four types based on their spatial relationship to the TEER device: Type 1, PISA center at a certain distance from the TEER device (D>R; 15 instances); Type 2, PISA adjacent to the TEER device (D<R; 37 instances); Type 3, PISA located inside the TEER device (3 instances); and Type 4, PISA located between two TEER devices (2 instances) (Figure 3).

Figure 3 TEE images and CFD models for 4 types of PISA. Comparison of the 4 types of PISA echocardiography and CFD models: (A) PISA in TEE images; (B,C) the 3D morphology of PISA with and without the TEER device; (D) comparing the spatial shapes of PISA with the TEER device (in red) and without the TEER device (in green). CDFI, color Doppler flow imaging; CFD, computational fluid dynamics; LVOT, left ventricular outflow tract; MV, mitral valve; PISA, proximal isovelocity surface area; TEE, transesophageal echocardiography; TEER, transcatheter edge-to-edge repair.

The effect of TEER devices on the analysis of MR according to PISA

In the reconstructed planes of CFD model, the PISA radii were measured, and the EROA1 was calculated. After the TEER device was removed, EROA2 was calculated. The study found EROA1 to be greater than EROA2 (0.17±0.11 vs. 0.12±0.07; P<0.001). With the TEER device removed, the degree of regurgitation in 9 EROA assessments was reduced from moderate to mild, and in 1 assessment, from severe to moderate. This indicated that the TEER device led to an overestimation rate of PISA regurgitation severity of 17.5% (Figure 4).

Figure 4 Comparison of calculated EROA with and without the TEER device in CFD models. CFD, computational fluid dynamics; EROA, effective regurgitant orifice area; TEER, transcatheter edge-to-edge repair.

The effect of TEER devices on PISA at different positions

The CC (calculated as EROA2/EROA1) varied across different types of PISA. For Type 1 PISA and Type 2 PISA, the CC was 0.92±0.07 and 0.65±0.10, respectively. The three instances of Type 3 PISA had CC values of 1.81, 2.72, and 1.06, respectively. The two instances of Type 4 PISA had CC values of 0.30 and 0.31, respectively. There was a significant statistical difference in the CC values between Type 1 and Type 2 PISA (P<0.001).

The formula for correcting EROA measurement with PISA after TEER

Due to the substantial spatial deformation of Type 3 and Type 4 PISA, it was not possible to precisely define the distance D from the VC focus to the device. These types were not suitable for correction based on the hemispherical surface area formula and were therefore excluded. For the remaining 52 Type 1 and Type 2 PISAs, a significant correlation was observed between the correction factor and distance D (Figure 5). This led to the development of an EROA correction formula based on D, expressed as follows: EROA2 = EROA1 × (0.52D + 0.53).

Figure 5 The correlation between the distance from the midpoint of the mitral regurgitation orifice to the TEER device (D) and the CCs for EROA in Type 1 and Type 2 PISA. The dashed lines indicate the 95% confidence interval. CC, correction coefficient; D, distance from the midpoint of the mitral regurgitation orifice to the TEER device; EROA, effective regurgitant orifice area; PISA, proximal isovelocity surface area; TEER, transcatheter edge-to-edge repair.

Discussion

This study used CFD to examine the effect of TEER devices on mitral valve regurgitation, blood flow convergence, and regurgitation severity assessment. The principal findings are as follows: (I) Individualized MR models can be constructed with intraoperative multimodal fusion imaging data to evaluate the impact of TEER devices on the measurement of EROA using the blood flow convergence method. (II) There are four different positional and morphological types of PISA after TEER. The position of the TEER device relative to the MR orifice is a critical factor affecting the accuracy of postoperative EROA measurement via the PISA method. (III) The calculation of EROA for most post-TEER regurgitations can be corrected based on the relative position of the regurgitation orifice to the TEER device.

PISA method for evaluating regurgitation after TEER

The evaluation of residual mitral valve regurgitation post-TEER surgery can be conducted using several methods, including VC, regurgitation jet area, 3DVCA, 3D volumetric method, and PISA (1,6,7). VC and regurgitation jet area offer semiquantitative assessments and are significantly influenced by the imaging plane, especially in the presence of multiple regurgitation jets. 3DVCA is impacted by its lower temporal resolution, and its measurement is relatively complex and subject to influence by the settings of grayscale gain (8-11). The 3D volumetric method directly measures regurgitation volume but may be prone to significant errors due to the limitations in endocardial border detection in echocardiography and the elliptical shape of the left ventricular outflow tract (12). The PISA method is applicable for both TEE and transthoracic echocardiography (TTE), ensuring consistency across preoperative assessments, intraoperative monitoring, and postoperative follow-up. It is particularly useful in cases with multiple regurgitation jets as it allows for the overlay of multiple PISA areas. However, after TEER device implantation, the structural changes around the regurgitation orifice can alter the shape of PISA, reducing measurement accuracy. This study therefore used CFD technology to simulate the mitral valve regurgitation orifice and PISA shape after removal of the TEER device, aiming to clarify the effect of the TEER device on the accuracy of PISA method assessments.

The application of CFD technology in MR assessment

CFD technology allows for the setting of various hemodynamic parameters to observe the impact of different anatomical changes on the intracardiac blood flow field (13-15). Previous studies have simulated PISA in CFD and compared it with 3D TEE PISA (16). Our study focused on the change in PISA shape after TEER surgery, building models based on immediate postoperative 3D TEE data. To better replicate the patient’s intracardiac hemodynamic state, individualized left atrium and left ventricle models were reconstructed from cardiac CT data. These models were then integrated with 3D TEE images to create a more precise individualized model of mitral valve regurgitation.

The effect of PISA located on one side of the TEER device

In cases where PISA occurs on one side of the TEER device, the device may block blood flow convergence in certain directions, leading to an increased radius of convergence on the unblocked side. This scenario can result in an overestimation of EROA when calculated with the hemispherical formula. We found that among the 57 observed PISAs, 10 were qualitatively assessed one grade higher, potentially leading to misjudgments in intraoperative decisions. It was noted that in Type 1 PISA (where D>R), the convergence of blood flow was minimally affected by the TEER device, whereas in Type 2 PISA (where D<R), the intrusion of the TEER device significantly increased R, leading to more pronounced errors in EROA calculation. The study observed that Type 1 and Type 2 PISA accounted for the majority of post-TEER mitral valve regurgitations and could be corrected using the same formula, which could minimize the effect of the TEER device on PISA assessment. It is important to recognize that in patients with FMR and a portion of those with DMR, spatial changes in the regurgitation orifice occur, such as elongated elliptical orifices. These changes can lead to a significant deviation in the shape of the isovelocity surface from a hemispherical form (17,18). However, the primary focus of this study was to mitigate the impact of the TEER device and to ensure minimal changes in the anatomical structure around the regurgitation orifice pre- and postsurgery. This approach is intended to improve the consistency of evaluation methods before and after the procedure.

The spatial morphology changes for PISA inside the TEER device or between two devices

Type 3 PISA, which includes a location inside the TEER device, generally results from internal anatomical abnormalities, calcification, or residual leaflet prolapse. Its formation mechanisms are varied and have complex effects on blood flow convergence. As the TEER device directly covers the regurgitation orifice, blood flow converging perpendicular to the orifice is obstructed, altering the direction of most converging blood flow to become parallel with the valve leaflets and rendering it undetectable by color Doppler signal. Type 3 PISA is usually less visible, yet significant regurgitation jets still exist on the atrial side. Type 4 PISA, with PISA located between two devices, involves obstruction of converging blood flow from both sides. As a result, the shape of Type 4 PISA becomes flattened and is influenced by the distance between the two TEER devices. The shape of the PISA in these cases is significantly deformed and deviates from the hemispherical assumption, potentially rendering the blood flow convergence method inaccurate for EROA calculation.

Effect of TEER device dimensions on PISA

Although device dimensions could theoretically influence PISA, standard clips are usually much larger than the PISA radius. A sensitivity analysis in one CFD case, in which we virtually modified the device to simulate “narrower” or “shorter” clips (Figure 6), showed that moderate changes to clip width or length had minimal impact on PISA morphology.

Figure 6 Modifying the width and length of the TEER device in a post-TEER CFD model. (A) The original post-TEER CFD model. (B) The width of the TEER device is reduced (simulating a “narrower” clip). (C) The length of the TEER device on the ventricular side is reduced (simulating a “shorter” clip). The results show that moderate changes to the device’s length and width do not significantly affect the PISA measurement in this case. CFD, computational fluid dynamics; PISA, proximal isovelocity surface area; TEER, transcatheter edge-to-edge repair.

The clinical significance of this study

Accurate assessment of regurgitation severity is crucial for intraoperative decision-making and postoperative follow-up prognosis prediction. During the TEER procedure, after the release of the first device, if residual regurgitation exists, it may be necessary to quantitatively assess the severity of MR. Overlooking the device’s influence on blood flow convergence can lead to a larger measurement of the PISA radius, resulting in a misjudgment of the regurgitation severity. This could lead to the implantation of additional devices, potentially increasing mitral valve stenosis and consequently elevating left atrial pressure, which may adversely affect patient prognosis.

During the TEER procedure, rapid correction of the EROA assessment can be made based on the relative positions of the PISA and TEER devices. The average CC for Type 1 PISA was 0.92, while that for Type 2 was 0.65. This facilitates a more accurate and consistent measurement of EROA, aiding physicians in making optimal interventional decisions.

During postoperative follow-up, it is also important to consider the effect of the device on blood flow convergence and to comprehensively evaluate the relative positions of different PISAs and TEER devices. This approach helps in the accurate and stable assessment of mitral valve regurgitation status. These evaluations are particularly valuable in guiding the adjustments to postoperative medication and cardiac volume control, especially for patients with FMR.

Limitations

The study’s data were sourced from a single clinical center using various TEER devices, which may have slight differences in spatial structure and function. Although the study had insufficient sample sizes for Types 3 and 4 PISAs for statistical analysis, most post-TEER PISAs were Types 1 and 2. The correction formula derived from CFD simulations is effective in minimizing the impact of most TEER devices in these cases.

In the CFD modeling, we employed a rigid wall model with a pressure boundary to represent the left ventricle, which limited our ability to accurately assess wall stress and fluid-structure interaction. Although a moving wall model would better reflect physiological conditions, the lack of precise, patient-specific motion data preclude its use, as an inaccurately defined moving boundary could introduce significant errors. In contrast, the pressure boundary approach allows for calibration of the CFD model against the patient’s echocardiographic measurements, ensuring high fidelity in the region of interest.

Conclusions

Individualized CFD models can be used to assess the impact of TEER devices on PISA. For types 1 and 2 PISA, CCs based on echocardiography data can be applied to reduce or eliminate the influence of TEER devices on the calculation of EROA.

Acknowledgments

None.

Footnote

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-772/dss

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-772/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The Ethics Committee at Renmin Hospital of Wuhan University approved the study protocol (No. WDRY2021-K186). For the retrospective analysis of imaging and clinical data, individual consent was waived by the Ethics Committee, as the study involved non-invasive computational modeling based on routinely acquired clinical imaging data. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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(English Language Editor: J. Gray)