Lifetime Management for Aortic Stenosis: Strategy and Decision Making in the Current Era.

Aortic stenosis (AS), the most common valvular disease in the western world has been traditionally treated with surgical aortic valve replacement (SAVR) but is increasingly treated by transcatheter aortic valve replacement (TAVR). While patients over age 65 are preferably treated with bioprosthetic tissue valves, there is considerable uncertainty in the choice between TAVR and SAVR. We present various considerations for optimizing the life-long management of patients receiving bioprosthetic valves (SAVR or TAVR). To maximize life expectancy and minimize cumulative lifetime risk, we suggest decision making individualized for patient anatomy and overall (current and future) risk.

Effects of implantation height on the performance of a redo transcatheter aortic valve replacement using a balloon-expandable valve.

Objective: The use of the transcatheter aortic valve in low-risk patients might lead to a second intervention due to the deterioration of the first 1. Understanding the implantation height is key to an effective redo transcatheter aortic valve replacement treatment. Methods: The effects of implantation height on the performance of a balloon-expandable valve within a self-expandable valve were assessed using hemodynamic testing and particle image velocimetry. The hemodynamic performances, leaflet kinematics, and turbulent shear stresses were measured and compared. Results: When a second balloon-expandable valve was positioned at varying heights relative to the first self-expandable valve, the leaflet motion of the first valve transitioned from free opening and closing to overhanging, and eventually to being entirely pinned to the stent, forming a neo-skirt. When the leaflets of the self-expandable valve could move freely, a decrease in regurgitation fraction was observed, but with an increased pressure gradient across the valve. Flow visualization indicated that the overhanging leaflets disrupted the flow, generating a higher level of turbulence. Conclusions: This study suggests that the overhanging leaflets should be avoided, whereas the other 2 scenarios should be carefully evaluated based on an individual patient's anatomy and the cause of failure of the first valve.

Patient-specific 3D in vitro modeling and fluid dynamic analysis of primary pulmonary vein stenosis.

Introduction: Primary pulmonary vein stenosis (PVS) is a rare congenital heart disease that proves to be a clinical challenge due to the rapidly progressive disease course and high rates of treatment complications. PVS intervention is frequently faced with in-stent restenosis and persistent disease progression despite initial venous recanalization with balloon angioplasty or stenting. Alterations in wall shear stress (WSS) have been previously associated with neointimal hyperplasia and venous stenosis underlying PVS progression. Thus, the development of patient-specific three-dimensional (3D) in vitro models is needed to further investigate the biomechanical outcomes of endovascular and surgical interventions. Methods: In this study, deidentified computed tomography images from three patients were segmented to generate perfusable phantom models of pulmonary veins before and after catheterization. These 3D reconstructions were 3D printed using a clear resin ink and used in a benchtop experimental setup. Computational fluid dynamic (CFD) analysis was performed on models in silico utilizing Doppler echocardiography data to represent the in vivo flow conditions at the inlets. Particle image velocimetry was conducted using the benchtop perfusion setup to analyze WSS and velocity profiles and the results were compared with those predicted by the CFD model. Results: Our findings indicated areas of undesirable alterations in WSS before and after catheterization, in comparison with the published baseline levels in the healthy in vivo tissues that may lead to regional disease progression. Discussion: The established patient-specific 3D in vitro models and the developed in vitro-in silico platform demonstrate great promise to refine interventional approaches and mitigate complications in treating patients with primary PVS.

Modeling of valve-in-valve transcatheter aortic valve implantation after aortic root replacement using a 3-dimensional artificial intelligence algorithm.

OBJECTIVE: Aortic root replacement requires construction of a composite valve-graft and reimplantation of coronary arteries. This study assessed the feasibility of valve-in-valve transcatheter aortic valve implantation after aortic root replacement. METHODS: A retrospective review was conducted on 74 consecutive patients who received a composite valve-graft at a single institution from 2019 to 2021. Forty patients had bioprosthetic valves with adequate postoperative gated computed tomographic angiography scans. Computational simulations of balloon and self-expanding transcatheter valve deployments were performed. The modeled coronary distances were compared with traditional, manually measured valve-to-coronary distances. RESULTS: There was a statistically significant difference in the modeled versus manual measurements of valve to coronary distances for all patients regardless of valve type or coronary artery analyzed (P < .05). Most patients are low risk for coronary obstruction per 3-dimensional modeling, including those with a valve-to-coronary distance <4 mm. Only 1 patient (2.5%) was at risk for coronary obstruction for the left coronary artery using a balloon valve. No other valve combination was considered high risk of coronary obstruction. Five patients (12.5%) were at risk for possible valve stent deformation at the outflow, due to angulation at the graft anastomosis. CONCLUSIONS: Following aortic root replacement, all patients were candidates for valve-in-valve procedure using 1 or both types of transcatheter heart valves. Self-expanding valves may be at higher risk for stent frame deformation at graft anastomotic lines and balloon-expandable valves may be at higher risk of coronary obstruction.

Beyond Static Planning: Computational Predictive Modeling to Avoid Coronary Artery Occlusion in TAVR.

BACKGROUND: Coronary artery occlusion (CO) during transcatheter aortic valve replacement (TAVR) is a devastating complication. The objective of this study was to assess the clinical impact of a computational predictive modeling algorithm for CO during TAVR planning. METHODS: From January 2020 to December 2022, 116 patients (7.6%) who underwent TAVR evaluation were deemed to be at increased risk of CO on the basis of traditional criteria. Patients underwent prospective computational modeling (DASI Simulations) to assess their risk of CO during TAVR; procedural modifications and clinical results were reviewed retrospectively. RESULTS: Of the 116 patients at risk for CO by traditional methodology, 53 had native aortic valve stenosis (45.7%), 47 had undergone previous surgical AVR (40.5%), and 16 had undergone previous TAVR (13.8%). Transcatheter valve choice, size, or implantation depth was modeled for all patients. Computational modeling predicted an increased risk of CO in 39 of 116 (31.9%) patients. Within this subcohort, 29 patients proceeded with TAVR. Procedural modifications to augment the risk of CO included bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction during TAVR (n = 10), chimney coronary stents (n = 8), and coronary access without stents (n = 3). There were no episodes of coronary artery compromise among patients after TAVR, either for those predicted to be at high risk of CO (with procedural modifications) or those predicted to be at low risk (standard TAVR). CONCLUSIONS: The use of preoperative simulations for TAVR in patient-specific geometry through computational predictive modeling of CO is an effective enhancement to procedure planning.

Hemodynamics of the VenusP Valve System™-an in vitro study.

This study aims to evaluate the fluid dynamic characteristics of the VenusP Valve System™ under varying cardiac outputs in vitro. A thorough hemodynamic study of the valve under physiological cardiac conditions was conducted and served as an independent assessment of the performance of the valve. Flow fields downstream of the valve near the pulmonary bifurcation were quantitatively studied by two-dimensional Particle Image Velocimetry (PIV). The obtained flow field was analyzed for potential regions of flow stasis and recirculation, and elevated shear stress and turbulence. High-speed en face imaging capturing the leaflet motion provided data for leaflet kinematic modeling. The experimental conditions for PIV studies were in accordance with ISO 5840-1:2021 standard, and two valves with different lengths and different orientations were studied. Results show good hemodynamics performance for the tested valves according to ISO 5840 standard without significant regions of flow stasis. Observed shear stress values are all well below established hemolysis limits.

Targeted Rapamycin Delivery via Magnetic Nanoparticles to Address Stenosis in a 3D Bioprinted in Vitro Model of Pulmonary Veins.

Vascular cell overgrowth and lumen size reduction in pulmonary vein stenosis (PVS) can result in elevated PV pressure, pulmonary hypertension, cardiac failure, and death. Administration of chemotherapies such as rapamycin have shown promise by inhibiting the vascular cell proliferation; yet clinical success is limited due to complications such as restenosis and off-target effects. The lack of in vitro models to recapitulate the complex pathophysiology of PVS has hindered the identification of disease mechanisms and therapies. This study integrated 3D bioprinting, functional nanoparticles, and perfusion bioreactors to develop a novel in vitro model of PVS. Bioprinted bifurcated PV constructs are seeded with endothelial cells (ECs) and perfused, demonstrating the formation of a uniform and viable endothelium. Computational modeling identified the bifurcation point at high risk of EC overgrowth. Application of an external magnetic field enabled targeting of the rapamycin-loaded superparamagnetic iron oxide nanoparticles at the bifurcation site, leading to a significant reduction in EC proliferation with no adverse side effects. These results establish a 3D bioprinted in vitro model to study PV homeostasis and diseases, offering the potential for increased throughput, tunability, and patient specificity, to test new or more effective therapies for PVS and other vascular diseases.

3D Characterization of the Aortic Valve and Aortic Arch in Bicuspid Aortic Valve Patients.

Patients with bicuspid aortic valve (BAV) commonly have associated aortic stenosis and aortopathy. The geometry of the aortic arch and BAV is not well defined quantitatively, which makes clinical classifications subjective or reliant on limited 2D measurements. The goal of this study was to characterize the 3D geometry of the aortic arch and BAV using objective and quantitative techniques. Pre-TAVR computed tomography angiogram (CTA) in patients with BAV and aortic stenosis (AS) were analyzed (n = 59) by assessing valve commissural angle, presence of a fused region, percent of fusion, and calcium volume. The ascending aorta and aortic arch were reconstructed from patient-specific imaging segmentation to generate a centerline and calculate maximum curvature and maximum area change for the ascending aorta and the descending aorta. Aortic valve commissural angle signified a bimodal distribution suggesting tricuspid-like (≤ 150°, 52.5% of patients) and bicuspid-like (> 150°, 47.5%) morphologies. Tricuspid like was further classified by partial (10.2%) or full (42.4%) fusion, and bicuspid like was further classified into valves with fused region (27.1%) or no fused region (20.3%). Qualitatively, the aortic arch was found to have complex patient-specific variations in its 3D shape with some showing extreme diameter changes and kinks. Quantitatively, subgroups were established using maximum curvature threshold of 0.04 and maximum area change of 30% independently for the ascending and descending aorta. These findings provide insight into the geometric structure of the aortic valve and aortic arch in patients presenting with BAV and AS where 3D characterization allows for quantitative classification of these complex anatomic structures.

Sensitivity of Post-TAVR Hemodynamics to the Distal Aortic Arch Anatomy: A High-Fidelity CFD Study.

PURPOSE: Patient-specific simulations of transcatheter aortic valve (TAV) using computational fluid dynamics (CFD) often rely on assumptions regarding proximal and distal anatomy due to the limited availability of high-resolution imaging away from the TAV site and the primary research focus being near the TAV. However, the influence of these anatomical assumptions on computational efficiency and resulting flow characteristics remains uncertain. This study aimed to investigate the impact of different distal aortic arch anatomies-some of them commonly used in literature-on flow and hemodynamics in the vicinity of the TAV using large eddy simulations (LES). METHODS: Three aortic root anatomical configurations with four representative distal aortic arch types were considered in this study. The arch types included a 90-degree bend, an idealized distal aortic arch anatomy, a clipped version of the idealized distal aortic arch, and an anatomy extruded along the normal of segmented anatomical boundary. Hemodynamic parameters both instantaneous and time-averaged such as Wall Shear Stress (WSS), and Oscillatory Shear Index (OSI) were derived and compared from high-fidelity CFD data. RESULTS: While there were minor differences in flow and hemodynamics across the configurations examined, they were generally not significant within our region of interest i.e., the aortic root. The choice of extension type had a modest impact on TAV hemodynamics, especially in the vicinity of the TAV with variations observed in local flow patterns and parameters near the TAV. However, these differences were not substantial enough to cause significant deviations in the overall flow and hemodynamic characteristics. CONCLUSIONS: The results suggest that under the given configuration and boundary conditions, the type of outflow extension had a modest impact on hemodynamics proximal to the TAV. The findings contribute to a better understanding of flow dynamics in TAV configurations, providing insights for future studies in TAV-related experiments as well as numerical simulations. Additionally, they help mitigate the uncertainties associated with patient-specific geometries, offering increased flexibility in computational modeling.

Predicting pressure gradient using artificial intelligence for transcatheter aortic valve replacement.

Objective: After transcatheter aortic valve replacement, the mean transvalvular pressure gradient indicates the effectiveness of the therapy. The objective is to develop artificial intelligence to predict the post-transcatheter aortic valve replacement aortic valve pressure gradient and aortic valve area from preprocedural echocardiography and computed tomography data. Methods: A retrospective study was conducted on patients who underwent transcatheter aortic valve replacement due to aortic valve stenosis. A total of 1091 patients were analyzed for pressure gradient predictions (mean age 76.8 ± 9.2 years, 57.8% male), and 1063 patients were analyzed for aortic valve area predictions (mean age 76.7 ± 9.3 years, 57.2% male). An artificial intelligence learning model was trained (training: n = 663 patients, validation: n = 206 patients) and tested (testing: n = 222 patients) to predict pressure gradient, and a separate artificial intelligence learning model was trained (training: n = 640 patients, validation: n = 218 patients) and tested (testing: n = 205 patients) for predicting aortic valve area. Results: The mean absolute error for pressure gradient and aortic valve area predictions was 3.0 mm Hg and 0.45 cm2, respectively. Valve sheath size, body surface area, and age were determined to be the top 3 predictors for pressure gradient, and valve sheath size, left ventricular ejection fraction, and aortic annulus mean diameter were identified to be the top 3 predictors of post-transcatheter aortic valve replacement aortic valve area. A training dataset size of more than 500 patients demonstrated good robustness of the artificial intelligence models for pressure gradient and aortic valve area. Conclusions: The artificial intelligence-based algorithm has demonstrated potential in predicting post-transcatheter aortic valve replacement transvalvular pressure gradient predictions for patients with aortic valve stenosis. Further studies are necessary to differentiate pressure gradient between valve types.

Differential Impact of Blood Pressure Control Targets on Epicardial Coronary Flow After Transcatheter Aortic Valve Replacement.

Background: The cause for the association between increased cardiovascular mortality rates and lower blood pressure (BP) after aortic valve replacement (AVR) is unclear. This study aims to assess how the epicardial coronary flow (ECF) after AVR varies as BP levels are changed in the presence of a right coronary lesion. Methods: The hemodynamics of a 3D printed aortic root model with a SAPIEN 3 26 deployed were evaluated in an in vitro left heart simulator under a range of varying systolic blood pressure (SBP) and diastolic blood pressure (DBP). ECF and the flow ratio index were calculated. Flow index value <0.8 was considered a threshold for ischemia. Results: As SBP decreased, the average ECF decreased below the physiological coronary minimum at 120 mmHg. As DBP decreased, the average ECF was still maintained above the physiological minimum. The flow ratio index was >0.9 for SBP ≥130 mmHg. However, at an SBP of 120 mmHg, the flow ratio was 0.63 (p ≤ 0.0055). With decreasing DBP, no BP condition yielded a flow ratio index that was less than 0.91. Conclusions: Reducing BP to the current recommended levels assigned for the general population after AVR in the presence of coronary artery disease may require reconsideration of levels and treatment priority. Additional studies are needed to fully understand the changes in ECF dynamics after AVR in the presence and absence of coronary artery disease.

Reduced Order Modeling for Real-Time Stent Deformation Simulations of Transcatheter Aortic Valve Prostheses.

Computational modeling can be a critical tool to predict deployment behavior for transcatheter aortic valve replacement (TAVR) in patients with aortic stenosis. However, due to the mechanical complexity of the aortic valve and the multiphysics nature of the problem, described by partial differential equations (PDEs), traditional finite element (FE) modeling of TAVR deployment is computationally expensive. In this preliminary study, a PDEs-based reduced order modeling (ROM) framework is introduced for rapidly simulating structural deformation of the Medtronic Evolut R valve stent frame. Using fifteen probing points from an Evolut model with parametrized loads enforced, 105 FE simulations were performed in the so-called offline phase, creating a snapshot library. The library was used in the online phase of the ROM for a new set of applied loads via the proper orthogonal decomposition-Galerkin (POD-Galerkin) approach. Simulations of small radial deformations of the Evolut stent frame were performed and compared to full order model (FOM) solutions. Linear elastic and hyperelastic constitutive models in steady and unsteady regimes were implemented within the ROM. Since the original POD-Galerkin method is formulated for linear problems, specific methods for the nonlinear terms in the hyperelastic case were employed, namely, the Discrete Empirical Interpolation Method. The ROM solutions were in strong agreement with the FOM in all numerical experiments, with a speed-up of at least 92% in CPU Time. This framework serves as a first step toward real-time predictive models for TAVR deployment simulations.

Development of Novel Sutureless Balloon Expandable Fetal Heart Valve Device Using Absorbable Polycaprolactone Leaflets.

Congenital heart disease (CHD) accounts for nearly one-third of all congenital defects, and patients often require repeated heart valve replacements throughout their lives, due to failed surgical repairs and lack of durability of bioprosthetic valve implants. This objective of this study is to develop and in vitro test a fetal transcatheter pulmonary valve replacement (FTPVR) using sutureless techniques to attach leaflets, as an option to correct congenital defects such as pulmonary atresia with intact ventricular septum (PA/IVS), in utero. A balloon expandable design was analyzed using computational simulations to identify areas of failure. Five manufactured valves were assembled using the unique sutureless approach and tested in the fetal right heart simulator (FRHS) to evaluate hemodynamic characteristics. Computational simulations showed that the commissural loads on the leaflet material were significantly reduced by changing the attachment techniques. Hemodynamic analysis showed an effective orifice area of 0.08 cm2, a mean transvalvular pressure gradient of 7.52 mmHg, and a regurgitation fraction of 8.42%, calculated over 100 consecutive cardiac cycles. In conclusion, the FTPVR exhibited good hemodynamic characteristics, and studies with biodegradable stent materials are underway.

Hydrogel-polyurethane fiber composites with enhanced microarchitectural control for heart valve replacement.

Polymeric heart valves offer the potential to overcome the limited durability of tissue based bioprosthetic valves and the need for anticoagulant therapy of mechanical valve replacement options. However, developing a single-phase material with requisite biological properties and target mechanical properties remains a challenge. In this study, a composite heart valve material was developed where an electrospun mesh provides tunable mechanical properties and a hydrogel coating confers an antifouling surface for thromboresistance. Key biological responses were evaluated in comparison to glutaraldehyde-fixed pericardium. Platelet and bacterial attachment were reduced by 38% and 98%, respectively, as compared to pericardium that demonstrated the antifouling nature of the hydrogel coating. There was also a notable reduction (59%) in the calcification of the composite material as compared to pericardium. A custom 3D-printed hydrogel coating setup was developed to make valve composites for device-level hemodynamic testing. Regurgitation fraction (9.6 ± 1.8%) and effective orifice area (1.52 ± 0.34 cm2 ) met ISO 5840-2:2021 requirements. Additionally, the mean pressure gradient was comparable to current clinical bioprosthetic heart valves demonstrating preliminary efficacy. Although the hemodynamic properties are promising, it is anticipated that the random microarchitecture will result in suboptimal strain fields and peak stresses that may accelerate leaflet fatigue and degeneration. Previous computational work has demonstrated that bioinspired fiber microarchitectures can improve strain homogeneity of valve materials toward improving durability. To this end, we developed advanced electrospinning methodologies to achieve polyurethane fiber microarchitectures that mimic or exceed the physiological ranges of alignment, tortuosity, and curvilinearity present in the native valve. Control of fiber alignment from a random fiber orientation at a normalized orientation index (NOI) 14.2 ± 6.9% to highly aligned fibers at a NOI of 85.1 ± 1.4%. was achieved through increasing mandrel rotational velocity. Fiber tortuosity and curvilinearity in the range of native valve features were introduced through a post-spinning annealing process and fiber collection on a conical mandrel geometry, respectively. Overall, these studies demonstrate the potential of hydrogel-polyurethane fiber composite as a heart valve material. Future studies will utilize the developed advanced electrospinning methodologies in combination with model-directed fabrication toward optimizing durability as a function of fiber microarchitecture.

Engineered Extracellular Vesicle-Based Therapies for Valvular Heart Disease.

Introduction: Valvular heart disease represents a significant burden to the healthcare system, with approximately 5 million cases diagnosed annually in the US. Among these cases, calcific aortic stenosis (CAS) stands out as the most prevalent form of valvular heart disease in the aging population.  CAS is characterized by the progressive calcification of the aortic valve leaflets, leading to valve stiffening. While aortic valve replacement is the standard of care for CAS patients, the long-term durability of prosthetic devices is poor, calling for innovative strategies to halt  or reverse disease progression. Here, we explor the potential use of novel extracellular vesicle (EV)-based nanocarriers for delivering molecular payloads to the affected valve tissue. This approach aims to reduce inflammation and potentially promote resorption of the calcified tissue. Methods: Engineered EVs loaded with the reprogramming myeloid transcription factors, CEBPA and Spi1, known to mediate the transdifferentiation of committed endothelial cells into macrophages. We evaluated the ability of these engineered EVs to deliver DNA and transcripts encoding CEBPA and Spil into calcified aortic valve tissue obtained from patients undergoing valve replacement due to aortic stenosis. We also investigated whether these EVs could induce the transdifferentiation of endothelial cells into macrophage-like cells. Results: Engineered EVs loaded with CEBPA + Spi1 were successfully derived from human dermal fibroblasts. Peak EV loading was found to be at 4 h after nanotransfection of donor cells.  These CEBPA + Spi1 loaded EVs effectively transfected aortic valve cells, resulting in the successful induction of transdifferentiation, both in vitro with  endothelial cells and ex vivo with valvular endothelial cells, leading to the development of anti-inflammatory macrophage-like cells. Conclusions: Our findings highlight the potential of engineered EVs as a next generation nanocarrier to target aberrant calcifications on diseased heart valves. This development holds promise as a novel therapy for high-risk patients who may not be suitable candidates for valve replacement surgery. Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-023-00783-x.

Calcium Fracture and Device Over Expansion in Transcatheter Aortic Valve Replacement for Bicuspid Aortic Valves.

Transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve disease (BAV) has potential risks of under expansion and non-circularity which may compromise long-term durability. This study aims to investigate calcium fracture and balloon over expansion in balloon-expandable TAVs on the stent deformation with the aid of simulation. BAV patients treated with the SAPIEN 3 Ultra with pre- and post-TAVR CTs were analyzed (n = 8). Simulations of the stent deployment were performed (1) with baseline simulation allowing calcium fracture, (2) without allowable calcium fracture and (3) with balloon over expansion (1 mm larger diameter). When compared to post CT, baseline simulations had minimal error in expansion (2.5% waist difference) and circularity (3.0% waist aspect ratio difference). When compared to baseline, calcium fracture had insignificant impact on the expansion (- 0.5% average waist difference) and circularity (- 1.6% average waist aspect ratio difference). Over expansion had significantly larger expansion compared to baseline (15.4% average waist difference) but had insignificant impact on the circularity (- 0.5% waist aspect ratio difference). We conclude that stent deformation can be predicted with minimal error, calcium fracture has small differences on the final stent deformation except in extreme calcified cases, and balloon over expansion expands the waist closer to nominal values.

An In-Vitro Study of the Flow Past a Transcatheter Aortic Valve Using Time-Resolved 3D Particle Tracking.

The performance of a transcatheter aortic valve (TAV) can be evaluated by analyzing the flow field downstream of the valve. However, three dimensional flow and pressure fields, and particle residence time, a quantity closely related to thrombosis risk, are challenging to obtain. This experimental study aims to provide a comprehensive 3D measurement of the flow field downstream of an Edwards SAPIEN 3 using time-resolved 3D particle tracking velocimetry (3D PTV) with Shake-the-Box (STB) algorithm. The valve was deployed in an idealized aorta model and tested in a left heart simulator under physiological conditions. Detailed 3D vortical structures, pressure distributions, and particle residence time were obtained by analyzing the 3D particle tracks. Results have shown large-scale retrograde flow entering the sinuses of the TAV at systole, reducing flow stasis there. However, the 3D particle tracks reveal that the retrograde flow has a high residence time and might have already experienced high shear stress near the main jet. Thus by only focusing on the flow in the sinus region is not sufficient to evaluate the leaflet thrombosis risk, and the flow downstream of the valve should be taken into consideration. The unique perspectives offered by 3D PTV are important when evaluating the performance of the TAVs.

Towards Longitudinal Monitoring of Leaflet Mobility in Prosthetic Aortic Valves via In-Situ Pressure Sensors: In-Silico Modeling and Analysis.

BACKGROUND: Transcatheter aortic valves (TAVs) are susceptible to leaflet thrombosis which may lead to thromboembolic events, and early detection and intervention are believed to be the key to avoiding such adverse outcomes. An embedded sensor system installed on the valve stent, coupled with an appropriate machine learning-based continuous monitoring algorithm can facilitate early detection to predict severity of reduced leaflet motion (RLM) and avoid adverse outcomes. METHODS: We present a data-driven, in silico, proof-of-concept analysis of a pressure microsensor based system for quantifying RLM in TAVs. We generate a dataset of 21 high-fidelity transvalvular flow simulations with healthy and mildly stenotic TAVs to train a logistic regression model to correlate individual leaflet mobility in each simulation with principal components of corresponding hemodynamic pressure recorded at strategic locations of the TAV stent. A separate test dataset of 7 simulations is also generated for prospective assessment of model performance. RESULTS: An array of 6 sensors embedded on the TAV stent, with two sensors tracking individual leaflet, successfully correlates leaflet mobility with recorded pressure. The sensors are placed along leaflet centerlines, one in the sinus, and the other at the sino-tubular junction. The regression model is tuned using cross-validation to achieve high accuracy on both training (R2 = 0.93) and test (R2 = 0.77) sets. CONCLUSION: Discrete blood pressure recordings on TAV stents can be successfully correlated with individual leaflet mobility. Further development of this technology can enable longitudinal monitoring of TAVs and early detection of valve failure.