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  • Quantitative biomechanical optimization of neochordal implantation location on mitral leaflets during valve repair. JTCVS techniques Pandya, P. K., Wilkerson, R. J., Imbrie-Moore, A. M., Zhu, Y., Marin-Cuartas, M., Park, M. H., Woo, Y. J. 2022; 14: 89-93


    Objective: Suture pull-out remains a significant mechanism of long-term neochordal repair failure, as demonstrated by clinical reports on recurrent mitral valve regurgitation and need for reoperation. The objective of this study was to provide a quantitative comparison of suture pull-out forces for various neochordal implantation locations.Methods: Posterior leaflets were excised from fresh porcine mitral valves (n=54) and fixed between two 3-dimensional-printed plates. Gore-Tex CV-5 sutures (WL Gore & Associates Inc) were placed with distances from the leading edge and widths between anchoring sutures with values of 2mm, 6mm, and 10mm for a total of 9 groups (n=6 per group). Mechanical testing was performed using a tensile testing machine to evaluate pull-out force of the suture through the mitral valve leaflet.Results: Increasing the suture anchoring width improved failure strength significantly across all leading-edge distances (P<.001). Additionally, increasing the leading-edge distance from 2mm to 6mm increased suture pull-out forces significantly across all suture widths (P<.001). For 6-mm and 10-mm widths, increasing the leading-edge distance from 6mm to 10mm increased suture pull-out forces by an average of 3.58±0.15N; in comparison, for leading-edge distances of 6mm and 10mm, increasing the suture anchoring width from 6mm to 10mm improves the force by an average of 7.09±0.44N.Conclusions: Increasing suture anchoring width and leading-edge distance improves the suture pull-out force through the mitral leaflet, which may optimize postrepair durability. The results suggest a comparative advantage to increasing suture anchoring width compared with leading-edge distance.

    View details for DOI 10.1016/j.xjtc.2022.05.008

    View details for PubMedID 35967240

  • Biomechanical Engineering Analysis of Pulmonary Valve Leaflet Hemodynamics and Kinematics in the Ross Procedure. Journal of biomechanical engineering Zhu, Y., Wilkerson, R., Pandya, P., Mullis, D., Wu, C., Madira, S., Marin-Cuartas, M., Park, M. H., Imbrie-Moore, A., Woo, Y. J. 2022


    Objectives The Ross procedure using the inclusion technique with anti-commissural plication (ACP) is associated with excellent valve hemodynamics and leaflet kinematics. The objective was to evaluate pulmonary cusp's biomechanics and fluttering by including coronary flow in the Ross procedure. Methods Ten porcine and five human pulmonary autografts were harvested from a meat abattoir and from heart transplant patients. Five porcine autografts without reinforcement served as controls. The other autografts were prepared using the inclusion technique with and without ACP (NACP). Hemodynamic and high-speed videography data were measured using the ex vivo heart simulator. Results Although porcine autografts showed similar leaflet rapid opening and closing mean velocities, human ACP compared to NACP autografts demonstrated lower leaflet rapid opening mean velocity in the right (p=.02) and left coronary cusps (p=.003). The porcine and human autograft leaflet rapid opening and closing mean velocities were similar in all cusps. Porcine autografts showed similar leaflet flutter frequencies in the left (p=.3) and non-coronary cusps (p=.4), but porcine NACP autografts vs. controls demonstrated higher leaflet flutter frequency in the right coronary cusp (p=.05). The human NACP vs. ACP autografts showed higher flutter frequency in the non-coronary cusp (p=.02). The leaflet flutter amplitudes were similar in all three cusps in both porcine and human autografts. Conclusions The ACP compared to NACP autografts in the Ross procedure was associated with more favorable leaflet kinematics. These results may translate to improved long-term durability of the pulmonary autografts.

    View details for DOI 10.1115/1.4055033

    View details for PubMedID 35864775

  • Efficacy of a Novel Posterior Leaflet Repair Device to Treat Secondary Mitral Regurgitation Using an Ex Vivo Heart Model STRUCTURAL HEART-THE JOURNAL OF THE HEART TEAM Kapadia, S. R., Harb, S. C., Hovest, T. J., Imbrie-Moore, A. M., Wilkerson, R. J., Woo, Y., Navia, J. L. 2022; 6 (1)
  • Large Animal Translational Validation of 3 Mitral Valve Repair Operations for Mitral Regurgitation Using a Mitral Valve Prolapse Model: A Comprehensive In Vivo Biomechanical Engineering Analysis. Circulation. Cardiovascular interventions Zhu, Y., Yajima, S., Park, M. H., Venkatesh, A., Stark, C. J., Tran, N. A., Walsh, S. K., Ethiraj, S., Wilkerson, R. J., Lin, L. E., Lee, S. H., Gates, K. Y., Arthur, J. D., Baker, S. W., Mullis, D. M., Wu, C. A., Harima, S., Pokhrel, B., Resuello, D., Bergamasco, H., Wu, M. A., Baccouche, B. M., Pandya, P. K., Elde, S., Wang, H., Woo, Y. J. 2024; 17 (4): e013196


    Various mitral repair techniques have been described. Though these repair techniques can be highly effective when performed correctly in suitable patients, limited quantitative biomechanical data are available. Validation and thorough biomechanical evaluation of these repair techniques from translational large animal in vivo studies in a standardized, translatable fashion are lacking. We sought to evaluate and validate biomechanical differences among different mitral repair techniques and further optimize repair operations using a large animal mitral valve prolapse model.Male Dorset sheep (n=20) had P2 chordae severed to create the mitral valve prolapse model. Fiber Bragg grating force sensors were implanted to measure chordal forces. Ten sheep underwent 3 randomized, paired mitral valve repair operations: neochord repair, nonresectional leaflet remodeling, and triangular resection. The other 10 sheep underwent neochord repair with 2, 4, and 6 neochordae. Data were collected at baseline, mitral valve prolapse, and after each repair.All mitral repair techniques successfully eliminated regurgitation. Compared with mitral valve prolapse (0.54±0.18 N), repair using neochord (0.37±0.20 N; P=0.02) and remodeling techniques (0.30±0.15 N; P=0.001) reduced secondary chordae peak force. Neochord repair further decreased primary chordae peak force (0.21±0.14 N) to baseline levels (0.20±0.17 N; P=0.83), and was associated with lower primary chordae peak force compared with the remodeling (0.34±0.18 N; P=0.02) and triangular resectional techniques (0.36±0.27 N; P=0.03). Specifically, repair using 2 neochordae resulted in higher peak primary chordal forces (0.28±0.21 N) compared with those using 4 (0.22±0.16 N; P=0.02) or 6 neochordae (0.19±0.16 N; P=0.002). No difference in peak primary chordal forces was observed between 4 and 6 neochordae (P=0.05). Peak forces on the neochordae were the lowest using 6 neochordae (0.09±0.11 N) compared with those of 4 neochordae (0.15±0.14 N; P=0.01) and 2 neochordae (0.29±0.18 N; P=0.001).Significant biomechanical differences were observed underlying different mitral repair techniques in a translational large animal model. Neochord repair was associated with the lowest primary chordae peak force compared to the remodeling and triangular resectional techniques. Additionally, neochord repair using at least 4 neochordae was associated with lower chordal forces on the primary chordae and the neochordae. This study provided key insights about mitral valve repair optimization and may further improve repair durability.

    View details for DOI 10.1161/CIRCINTERVENTIONS.123.013196

    View details for PubMedID 38626077

  • A 3D-Printed Externally Adjustable Symmetrically Extensible (EASE) Aortic Annuloplasty Ring for Root Repair and Aortic Valve Regurgitation. Cardiovascular engineering and technology Zhu, Y., Park, M. H., Wilkerson, R. J., Joo, H. C., Pandya, P. K., Woo, Y. J. 2024


    The valve-sparing aortic root replacement (VSARR) procedure was developed to preserve the aortic valve apparatus to replace aneurysmal aortic roots with synthetic grafts and to eliminate associated aortic regurgitation (AR). However, residual post-repair AR is not uncommon and has been found to be associated with recurrent AR and future reoperation.We designed and manufactured a 3D-printed, external adjustable symmetrically extensible (EASE) aortic annuloplasty ring that can symmetrically reduce the aortic annulus diameter via a radial constriction, compliant mechanism. An ex vivo porcine VSARR model with annular dilation and AR was developed (n = 4) and used for hemodynamic, echocardiography, and high-speed videography data collection.After ring annuloplasty repair using the EASE aortic ring, the regurgitant fraction decreased from 23.6 ± 6.9% from the VSARR model to 7.4 ± 5.6% (p = 0.05), which was similar to that measured from baseline with a regurgitant fraction of 10.2 ± 3.9% (p = 0.34). The leaflet coaptation height after annuloplasty repair also significantly increased from that measured in VSARR model (0.4 ± 0.1 cm) to 0.9 ± 0.1 cm (p = 0.0004), a level similar to that measured in baseline (1.1 ± 0.1 cm, p = 0.28).Using an ex vivo VSARR model, the EASE ring successfully reduced AR by reducing the annular diameter and improving leaflet coaptation. With its broad applicability and ease of use, this device has the potential to have a significant impact on patients suffering worldwide from AR due to root aneurysms.

    View details for DOI 10.1007/s13239-024-00709-2

    View details for PubMedID 38238600

    View details for PubMedCentralID 6562077

  • Chordal force profile after neochordal repair of anterior mitral valve prolapse: An ex vivo study. JTCVS open Yajima, S., Zhu, Y., Stark, C. J., Wilkerson, R. J., Park, M. H., Stefan, E., Woo, Y. J. 2023; 15: 164-172


    This study aimed to biomechanically evaluate the force profiles on the anterior primary and secondary chordae after neochord repair for anterior valve prolapse with varied degrees of residual mitral regurgitation using an ex vivo heart simulator.The experiment used 8 healthy porcine mitral valves. Chordal forces were measured using fiber Bragg grating sensors on primary and secondary chordae from A2 segments. The anterior valve prolapse model was generated by excising 2 primary chordae at the A2 segment. Neochord repair was performed with 2 pairs of neochords. Varying neochord lengths simulated postrepair residual mitral regurgitation with regurgitant fraction at >30% (moderate), 10% to 30% (mild), and <10% (perfect repair).Regurgitant fractions of baseline, moderate, mild, and perfect repair were 4.7% ± 0.8%, 35.8% ± 2.1%, 19.8% ± 2.0%, and 6.0% ± 0.7%, respectively (P < .001). Moderate had a greater peak force of the anterior primary chordae (0.43 ± 0.06 N) than those of baseline (0.19 ± 0.04 N; P = .011), mild (0.23 ± 0.05 N; P = .041), and perfect repair (0.21 ± 0.03 N; P = .006). In addition, moderate had a greater peak force of the anterior secondary chordae (1.67 ± 0.17 N) than those of baseline (0.64 ± 0.13 N; P = .003), mild (0.84 ± 0.24 N; P = .019), and perfect repair (0.68 ± 0.14 N; P = .001). No significant differences in peak and average forces on both primary and secondary anterior chordae were observed between the baseline and perfect repair as well as the mild and perfect repair.Moderate residual mitral regurgitation after neochord repair was associated with increased anterior primary and secondary chordae forces in our ex vivo anterior valve prolapse model. This difference in chordal force profile may influence long-term repair durability, providing biomechanical evidence in support of obtaining minimal regurgitation when repairing mitral anterior valve prolapse.

    View details for DOI 10.1016/j.xjon.2023.04.011

    View details for PubMedID 37808060

    View details for PubMedCentralID PMC10556825

  • An analytical, mathematical annuloplasty ring curvature model for planning of valve-in-ring transcatheter mitral valve replacement. JTCVS techniques Park, M. H., Marin-Cuartas, M., Sellke, M., Pandya, P. K., Zhu, Y., Wilkerson, R. J., Holzhey, D. M., Borger, M. A., Woo, Y. J. 2023; 20: 45-54


    An increasing number of high-risk patients with previous mitral valve annuloplasty require transcatheter mitral valve replacement due to recurrent regurgitation. Annulus dilation with a transcatheter balloon is often performed before valve-in-ring transcatheter mitral valve replacement, which is believed to reduce misalignment and paravalvular leakage, yet little evidence exists to support this practice. Our objective was to generate intuitive annuloplasty ring analyses for improved valve-in-ring transcatheter mitral valve replacement planning.We generated a mathematical model that calculates image-tracked differential ring curvature to build quantifications for improved planning for valve-in-ring procedures. Carpentier-Edwards Physio M24 and M30 (n = 2 each), Physio II M24 and M26 (n = 3 each), LivaNova AnnuloFlex M26 (n = 2), and Edwards Geoform M28 (n = 2) rings were tested with a 30-mm Toray Inoue balloon inflated to maximum rated pressures.Curvature variance reduces with larger ring sizes, indicating that larger rings are initially more circular than smaller ones. Evaluated semi-rigid and rigid rings showed little to no difference between pre- and post-dilation states. Annuloflex rings (flexible band) showed a postdilation variance reduction of 32.83% (P < .001) followed by an increase after 10 minutes of relaxation that was still reduced by 19.62% relative to the initial state (P < .001).We discovered that balloon dilation does not significantly deform evaluated semi-rigid or rigid rings at maximum rated balloon pressures. This may mean that dilation for these conditions before valve-in-ring transcatheter mitral valve replacement is unnecessary. Our mathematical approach creates a foundation for extended classification of this practice, providing meaningful quantification of ring geometry.

    View details for DOI 10.1016/j.xjtc.2023.03.022

    View details for PubMedID 37555034

    View details for PubMedCentralID PMC10405166

  • Ex Vivo Modeling of Atrioventricular Valve Mechanics in Single Ventricle Physiology. Annals of biomedical engineering Moye, S. C., Kidambi, S., Lee, J. Y., Cowles, T. H., Gilligan-Steinberg, S. D., Bryan, A. Y., Wilkerson, R., Woo, Y. J., Ma, M. R. 2023


    Single ventricle physiology (SVP) is used to describe any congenital heart lesion that is unable to support independent pulmonary and systemic circulations. Current treatment strategies rely on a series of palliation surgeries that culminate in the Fontan physiology, which relies on the single functioning ventricle to provide systemic circulation while passively routing venous return through the pulmonary circulation. Despite significant reductions in early mortality, the presence of atrioventricular valve (AVV) regurgitation is a key predictor of heart failure in these patients. We sought to evaluate the biomechanical changes associated with the AVV in SVP physiologies. Left and right ventricles were sutured onto patient-derived 3D-printed mounts and mounted into an ex vivo systemic heart simulator capable of reproducing Norwood, Glenn, Fontan and Late Fontan physiologies. We found that the tricuspid anterior leaflet experienced elevated maximum force, average force, and maximum yank compared to the posterior and septal leaflets. Between physiologies, maximum yank was greatest in the Norwood physiology relative to the Glenn, Fontan, and Late Fontan physiologies. These contrasting trends suggest that long- and short-term mechanics of AVV failure in single ventricle differ and that AVV interventions should account for asymmetries in force profiles between leaflets and physiologies.

    View details for DOI 10.1007/s10439-023-03178-1

    View details for PubMedID 36966247

    View details for PubMedCentralID 5371563

  • Biomechanical evaluation of aortic regurgitation from cusp prolapse using an ex vivo 3D-printed commissure geometric alignment device. Journal of cardiothoracic surgery Zhu, Y., Park, M. H., Imbrie-Moore, A., Wilkerson, R., Madira, S., Woo, Y. J. 2022; 17 (1): 303


    BACKGROUND: Aortic regurgitation (AR) is one of the most common cardiac valvular diseases, and it is frequently caused by cusp prolapse. However, the precise relationship of commissure position and aortic cusp prolapse with AR is not fully understood. In this study, we developed a 3D-printed commissure geometric alignment device to investigate the effect of commissure height and inter-commissure angle on AR and aortic cusp prolapse.METHODS: Three porcine aortic valves were explanted from hearts obtained from a meat abattoir and were mounted in the commissure geometric alignment device. Nine commissure configurations were tested for each specimen, exploring independent and concurrent effects of commissure height and inter-commissure angle change on AR and aortic cusp prolapse. Each commissure configuration was tested in our 3D printed ex vivo left heart simulator. Hemodynamics data, echocardiography, and high-speed videography were obtained.RESULTS: AR due to aortic cusp prolapse was successfully generated using our commissure geometric alignment device. Mean aortic regurgitation fraction measured for the baseline, high commissure, low commissure, high commissure and wide inter-commissure angle, high commissure and narrow inter-commissure angle, low commissure and wide inter-commissure angle, low commissure and narrow inter-commissure angle, wide commissure, and narrow commissure configurations from all samples were 4.6±1.4%, 9.7±3.7%, 4.2±0.5%, 11.7±5.8%, 13.0±8.5%, 4.8±0.9%, 7.3±1.7%, 5.1±1.2%, and 7.1±3.1%, respectively.CONCLUSIONS: AR was most prominent when commissure heights were changed from their native levels with concomitant reduced inter-commissure angle. Findings from this study provide important evidence demonstrating the relationship between commissure position and aortic cusp prolapse and may have a significant impact on patient outcomes after surgical repair of aortic valves.

    View details for DOI 10.1186/s13019-022-02049-5

    View details for PubMedID 36496476

  • Native and Post-Repair Residual Mitral Valve Prolapse Increases Forces Exerted on the Papillary Muscles: A Possible Mechanism for Localized Fibrosis? Circulation. Cardiovascular interventions Park, M. H., van Kampen, A., Melnitchouk, S., Wilkerson, R. J., Nagata, Y., Zhu, Y., Wang, H., Pandya, P. K., Morningstar, J. E., Borger, M. A., Levine, R. A., Woo, Y. J. 2022; 15 (12): e011928


    Recent studies have linked mitral valve prolapse to localized myocardial fibrosis, ventricular arrhythmia, and even sudden cardiac death independent of mitral regurgitation or hemodynamic dysfunction. The primary mechanistic theory is rooted in increased papillary muscle traction and forces due to prolapse, yet no biomechanical evidence exists showing increased forces. Our objective was to evaluate the biomechanical relationship between prolapse and papillary muscle forces, leveraging advances in ex vivo modeling and technologies. We hypothesized that mitral valve prolapse with limited hemodynamic dysfunction leads to significantly higher papillary muscle forces, which could be a possible trigger for cellular and electrophysiological changes in the papillary muscles and adjacent myocardium.We developed an ex vivo papillary muscle force transduction and novel neochord length adjustment system capable of modeling targeted prolapse. Using 3 unique ovine models of mitral valve prolapse (bileaflet or posterior leaflet prolapse), we directly measured hemodynamics and forces, comparing physiologic and prolapsing valves.We found that bileaflet prolapse significantly increases papillary muscle forces by 5% to 15% compared with an optimally coapting valve, which are correlated with statistically significant decreases in coaptation length. Moreover, we observed significant changes in the force profiles for prolapsing valves when compared with normal controls.We discovered that bileaflet prolapse with the absence of hemodynamic dysfunction results in significantly elevated forces and altered dynamics on the papillary muscles. Our work suggests that the sole reduction of mitral regurgitation without addressing reduced coaptation lengths and thus increased leaflet surface area exposed to ventricular pressure gradients (ie, billowing leaflets) is insufficient for an optimal repair.

    View details for DOI 10.1161/CIRCINTERVENTIONS.122.011928

    View details for PubMedID 36538583

  • Force Profiles of Single Ventricle Atrioventricular Leaflets in Response to Annular Dilation and Leaflet Tethering. Seminars in thoracic and cardiovascular surgery Kidambi, S., Moye, S. C., Lee, J., Cowles, T. H., Strong, E. B., Wilkerson, R., Paulsen, M. J., Woo, Y. J., Ma, M. R. 2022


    We sought to understand how leaflet forces change in response to annular dilation and leaflet tethering in single ventricle physiology. Explanted fetal bovine tricuspid valves were sutured onto image-derived annuli and ventricular mounts. Control valves (CV) were secured to a size-matched HLHS-type annulus and compared to: 1) normal tricuspid valves (NTV) secured to a size-matched saddle-shaped annulus, 2) HLHS-type annulus with leaflet tethering (LT), 3) HLHS-type annulus with annular dilation (DIL), or 5) a combined disease model with both dilation and tethering (DIS). The specimens were tested in a systemic heart simulator at various SVPs. Leaflet forces were measured using optical strain sensors sutured to each leaflet edge. Average force in the anterior leaflet was 43.2% lower in CV compared to NTV (p<0.001). LT resulted in a 6.6% increase in average forces on the anterior leaflet (p=0.04), 10.7% increase on the posterior leaflet (p=0.03), and 14.1% increase on the septal leaflet (p<0.001). In DIL, average septal leaflet forces increased relative to the control valves by 42.2% (p=0.01). In DIS, average leaflet forces increased by 54.8% in the anterior leaflet (p<0.001), 37.6% in the posterior leaflet (p=0.03), and 79.9% in the septal leaflet (p<0.001). The anterior leaflet experiences the highest forces in the normal tricuspid annulus under SVP conditions. Annular dilation resulted in an increase in forces on the septal leaflet and leaflet tethering resulted in an increase in forces across all 3 leaflets. Annular dilation and leaflet tethering combined resulted in the largest increase in leaflet forces across all 3 leaflets.

    View details for DOI 10.1053/j.semtcvs.2022.09.012

    View details for PubMedID 36455710

  • A novel accelerated fatigue testing system for pulsatile applications of cardiac devices using widely translatable cam and linkage-based mechanisms. Medical engineering & physics Park, M. H., Imbrie-Moore, A. M., Zhu, Y., Sellke, M., Marin-Cuartas, M., Wilkerson, R. J., Woo, Y. J. 2022; 109: 103896


    Fatigue testing of mechanical components is important for designing safe implantable medical prosthetics, and accelerated systems can be used to increase the speed of evaluation. We developed a platform for accelerated testing of linear force applications of cardiac devices, called the Fatigue Acceleration System Tester (FAST). FAST operates using a core translation mechanism, converting motor-driven rotary motion to linear actuation. The advantages of using this mechanism include 40x rate increases with largely 3D-printed components, versatility based on modular design paradigms, and accessible manufacturability with 3D-printable forms, enabling access for small and large research laboratories alike. FAST has been crucial in informing our designs for continuing device development. Over two fatigue cycle courses of 52 and 110 days, the motor cycled at rotational frequencies up to 1500 rpm, 43 times faster than those experienced in a typical heart and equating to approximate life cycles of five and ten years, respectively. In designing FAST, our goal was to accessibly bring a strong mechanical basis to study the long-term effects of repeated loading, and we present a design that can be applied across many industries to not only evaluate fatigue performance, but also generate any cycling linear motion.

    View details for DOI 10.1016/j.medengphy.2022.103896

    View details for PubMedID 36371080

  • A novel accelerated fatigue testing system for pulsatile applications of cardiac devices using widely translatable cam and linkage-based mechanisms MEDICAL ENGINEERING & PHYSICS Park, M. H., Imbrie-Moore, A. M., Zhu, Y., Sellke, M., Marin-Cuartas, M., Wilkerson, R. J., Woo, Y. 2022; 109
  • The Critical Biomechanics of Aortomitral Angle and Systolic Anterior Motion: Engineering Native Ex Vivo Simulation. Annals of biomedical engineering Park, M. H., Imbrie-Moore, A. M., Zhu, Y., Wilkerson, R. J., Wang, H., Park, G. H., Wu, C. A., Pandya, P. K., Mullis, D. M., Marin-Cuartas, M., Woo, Y. J. 2022


    Systolic anterior motion (SAM) of the mitral valve (MV) is a complex pathological phenomenon often occurring as an iatrogenic effect of surgical and transcatheter intervention. While the aortomitral angle has long been linked to SAM, the mechanistic relationship is not well understood. We developed the first ex vivo heart simulator capable of recreating native aortomitral biomechanics, and to generate models of SAM, we performed anterior leaflet augmentation and sequential undersized annuloplasty procedures on porcine aortomitral junctions (n=6). Hemodynamics and echocardiograms were recorded, and echocardiographic analysis revealed significantly reduced coaptation-septal distances confirming SAM (p=0.003) and effective manipulation of the aortomitral angle (p<0.001). Upon increasing the angle in our pathological models, we recorded significant increases (p<0.05) in both coaptation-septal distance and multiple hemodynamic metrics, such as aortic peak flow and effective orifice area. These results indicate that an increased aortomitral angle is correlated with more efficient hemodynamic performance of the valvular system, presenting a potential, clinically translatable treatment opportunity for reducing the risk and adverse effects of SAM. As the standard of care shifts towards surgical and transcatheter interventions, it is increasingly important to better understand SAM biomechanics, and our advances represent a significant step towards that goal.

    View details for DOI 10.1007/s10439-022-03091-z

    View details for PubMedID 36264407

  • A Novel Rheumatic Mitral Valve Disease Model with Ex Vivo Hemodynamic and Biomechanical Validation. Cardiovascular engineering and technology Park, M. H., Pandya, P. K., Zhu, Y., Mullis, D. M., Wang, H., Imbrie-Moore, A. M., Wilkerson, R., Marin-Cuartas, M., Woo, Y. J. 2022


    PURPOSE: Rheumatic heart disease is a major cause of mitral valve (MV) dysfunction, particularly in disadvantaged areas and developing countries. There lacks a critical understanding of the disease biomechanics, and as such, the purpose of this study was to generate the first ex vivo porcine model of rheumatic MV disease by simulating the human pathophysiology and hemodynamics.METHODS: Healthy porcine valves were altered with heat treatment, commissural suturing, and cyanoacrylate tissue coating, all of which approximate the pathology of leaflet stiffening and thickening as well as commissural fusion. Hemodynamic data, echocardiography, and high-speed videography were collected in a paired manner for control and model valves (n=4) in an ex vivo left heart simulator. Valve leaflets were characterized in an Instron tensile testing machine to understand the mechanical changes of the model (n=18).RESULTS: The model showed significant differences indicative of rheumatic disease: increased regurgitant fractions (p<0.001), reduced effective orifice areas (p<0.001), augmented transmitral mean gradients (p<0.001), and increased leaflet stiffness (p=0.025).CONCLUSION: This work represents the creation of the first ex vivo model of rheumatic MV disease, bearing close similarity to the human pathophysiology and hemodynamics, and it will be used to extensively study both established and new treatment techniques, benefitting the millions of affected victims.

    View details for DOI 10.1007/s13239-022-00641-3

    View details for PubMedID 35941509

  • Biomechanical analysis of neochordal repair error from diastolic phase inversion of static left ventricular pressurization. JTCVS techniques Park, M. H., Marin-Cuartas, M., Imbrie-Moore, A. M., Wilkerson, R. J., Pandya, P. K., Zhu, Y., Wang, H., Borger, M. A., Woo, Y. J. 2022; 12: 54-64


    Objective: Neochordal implantation is a common form of surgical mitral valve (MV) repair. However, neochord length is assessed using static left ventricular pressurization, leading surgeons to evaluate leaflet coaptation and valve competency when the left ventricle is dilating instead of contracting physiologically, referred to as diastolic phase inversion (DPI). We hypothesize that the difference in papillary muscle (PM) positioning between DPI and physiologic systole results in miscalculated neochord lengths, which might affect repair performance.Methods: Porcine MVs (n=6) were mounted in an exvivo heart simulator and PMs were affixed to robots that accurately simulate PM motion. Baseline hemodynamic and chordal strain data were collected, after which P2 chordae were severed to simulate posterior leaflet prolapse from chordal rupture and subsequent mitral regurgitation. Neochord implantation was performed in the physiologic and DPI static configurations.Results: Although both repairs successfully reduced mitral regurgitation, the DPI repair resulted in longer neochordae (2.19±0.4mm; P<.01). Furthermore, the hemodynamic performance was reduced for the DPI repair resulting in higher leakage volume (P=.01) and regurgitant fraction (P<.01). Peak chordal forces were reduced in the physiologic repair (0.57±0.11N) versus the DPI repair (0.68±0.12N; P<.01).Conclusions: By leveraging advanced exvivo technologies, we were able to quantify the effects of static pressurization on neochordal length determination. Our findings suggest that this post-repair assessment might slightly overestimate the neochordal length and that additional marginal shortening of neochordae might positively affect MV repair performance and durability by reducing load on surrounding native chordae.

    View details for DOI 10.1016/j.xjtc.2022.01.009

    View details for PubMedID 35403058

  • Efficacy of a Novel Posterior Leaflet Repair Device to Treat Secondary Mitral Regurgitation Using an Ex Vivo Heart Model. Structural heart : the journal of the Heart Team Kapadia, S. R., Harb, S. C., Hovest, T. J., Imbrie-Moore, A. M., Wilkerson, R. J., Woo, Y. J., Navia, J. L. 2022; 6 (1): 100023

    View details for DOI 10.1016/j.shj.2022.100023

    View details for PubMedID 37273469

    View details for PubMedCentralID PMC10236895

  • Ex vivo biomechanical analysis of flexible versus rigid annuloplasty rings in mitral valves using a novel annular dilation system. BMC cardiovascular disorders Zhu, Y., Imbrie-Moore, A. M., Wilkerson, R. J., Paulsen, M. J., Park, M. H., Woo, Y. J. 2022; 22 (1): 73


    BACKGROUND: Mitral annuloplasty rings restore annular dimensions to increase leaflet coaptation, serving a fundamental component in mitral valve repair. However, biomechanical evaluations of annuloplasty rings are lacking. We aim to biomechanically analyze flexible and rigid annuloplasty rings using an ex vivo mitral annular dilation model.METHODS: Juvenile porcine mitral valves (n=4) with intercommissural distance of 28mm were dilated to intercommissural distances of 40mm using a 3D-printed dilator and were sewn to an elastic mount. Fiber bragg grating sensors were anchored to native chordae to measure chordal forces. The valves were repaired using size 28 rigid and flexible annuloplasty rings in a random order. Hemodynamic data, echocardiography, and chordal force measurements were collected.RESULTS: Mitral annular dilation resulted in decreased leaflet coaptation height and increased mitral regurgitation fraction. Both the flexible and rigid annuloplasty rings effectively increased leaflet coaptation height compared to that post dilation. Rigid ring annuloplasty repair significantly decreased the mitral regurgitation fraction. Flexible annuloplasty ring repair reduced the chordal rate of change of force (7.1±4.4N/s versus 8.6±5.9N/s, p=0.02) and peak force (0.6±0.5N versus 0.7±0.6N, p=0.01) compared to that from post dilation. Rigid annuloplasty ring repair was associated with higher chordal rate of change of force (9.8±5.8N/s, p=0.0001) and peak force (0.7±0.5N, p=0.01) compared to that after flexible ring annuloplasty repair.CONCLUSIONS: Both rigid and flexible annuloplasty rings are effective in increasing mitral leaflet coaptation height. Although the rigid annuloplasty ring was associated with slightly higher chordal stress compared to that of the flexible annuloplasty ring, it was more effective in mitral regurgitation reduction. This study may help direct the design of an optimal annuloplasty ring to further improve patient outcomes.

    View details for DOI 10.1186/s12872-022-02515-x

    View details for PubMedID 35219298

  • Biomechanical engineering analysis of an acute papillary muscle rupture disease model using an innovative 3D-printed left heart simulator. Interactive cardiovascular and thoracic surgery Marin-Cuartas, M., Zhu, Y., Imbrie-Moore, A. M., Park, M. H., Wilkerson, R. J., Leipzig, M., Pandya, P. K., Paulsen, M. J., Borger, M. A., Woo, Y. J. 1800


    OBJECTIVES: The severity of acute papillary muscle (PM) rupture varies according to the extent and site of the rupture. However, the haemodynamic effects of different rupture variations are still poorly understood. Using a novel ex vivo model, we sought to study acute PM rupture to improve clinical management.METHODS: Using porcine mitral valves (n=32) mounted within an ex vivo left heart simulator, PM rupture was simulated. The mitral valve was divided into quadrants for analysis according to the PM heads. Acute PM rupture was simulated by incrementally cutting from 1/3 to the total number of chordae arising from 1 PM head of interest. Haemodynamic parameters were measured.RESULTS: Rupture >2/3 of the chordae from 1 given PM head or regurgitation fraction >60% led to markedly deteriorated haemodynamics. Rupture at the anterolateral PM had a stronger negative effect on haemodynamics than rupture at the posteromedial PM. Rupture occurring at the anterior head of the anterolateral PM led to more marked haemodynamic instability than rupture occurring at the other PM heads.CONCLUSIONS: The haemodynamic effects of acute PM rupture vary considerably according to the site and extent of the rupture. Rupture of ≤2/3 of chordae from 1 PM head or rupture at the posteromedial PM lead to less marked haemodynamics effects, suggesting a higher likelihood of tolerating surgery. Rupture at the anterolateral PM, specifically the anterior head, rupture of >2/3 of chordae from 1 PM head or regurgitation fraction >60% led to marked haemodynamic instability, suggesting the potential benefit from bridging strategies prior to surgery.

    View details for DOI 10.1093/icvts/ivab373

    View details for PubMedID 35022737

  • Biomechanical engineering comparison of four leaflet repair techniques for mitral regurgitation using a novel 3-dimensional-printed left heart simulator JTCVS TECHNIQUES Paulsen, M. J., Cuartas, M., Imbrie-Moore, A., Wang, H., Wilkerson, R., Farry, J., Zhu, Y., Ma, M., MacArthur, J. W., Woo, Y. 2021; 10: 244-251
  • Biomechanical engineering analysis of commonly utilized mitral neochordae. JTCVS open Marin-Cuartas, M., Imbrie-Moore, A. M., Zhu, Y., Park, M. H., Wilkerson, R., Leipzig, M., Borger, M. A., Woo, Y. J. 2021; 8: 263-275


    Objective: To evaluate the suture rupture forces of commonly clinically utilized neochord repair techniques to identify the most biomechanically resistant most biomechanically resistant technique.Methods: Several types of neochord techniques (standard interrupted neochordae, continuous running neochordae, and loop technique), numbers of neochordae, and suture calibers (polytetrafluoroethylene CV-3 to CV-6) were compared. To perform the tests, both ends of the neochordae were loaded in a tensile force analysis machine. During the test, the machine applied tension to the neochord until rupture was achieved. The tests were performed 3 times for each variation, and the rupture forces were averaged for statistical analysis.Results: Rupture force was significantly higher for running neochordae relative to interrupted neochordae (P<.01). However, a single rupture in the running technique resulted in failure of the complete neochord system. For both running and interrupted neochordae, a greater number of neochordae as well as a thicker suture caliber significantly increased the neochord rupture force (P<.01). The loop technique ruptured at significantly lower forces compared with the other 2 techniques (P<.01). A greater number of loops did not significantly increase the rupture force of loop neochordae. Observed rupture forces for all techniques were higher than those normally observed in physiologic conditions.Conclusions: Under experimental conditions, the running neochord technique has the best mechanical performance due to an increased rupture force. If using running neochordae, more than 1 independent set of multiple running neochordae are advised (ie, >2 independent sets of multiple running neochordae in each set).

    View details for DOI 10.1016/j.xjon.2021.07.040

    View details for PubMedID 36004068

  • Biomechanical engineering comparison of four leaflet repair techniques for mitral regurgitation using a novel 3-dimensional-printed left heart simulator. JTCVS techniques Paulsen, M. J., Cuartas, M. M., Imbrie-Moore, A., Wang, H., Wilkerson, R., Farry, J., Zhu, Y., Ma, M., MacArthur, J. W., Woo, Y. J. 2021; 10: 244-251


    Mitral valve repair is the gold standard treatment for degenerative mitral regurgitation; however, a multitude of repair techniques exist with little quantitative data comparing these approaches. Using a novel ex vivo model, we sought to evaluate biomechanical differences between repair techniques.Using porcine mitral valves mounted within a custom 3-dimensional-printed left heart simulator, we induced mitral regurgitation using an isolated P2 prolapse model by cutting primary chordae. Next, we repaired the valves in series using the edge-to-edge technique, neochordoplasty, nonresectional remodeling, and classic leaflet resection. Hemodynamic data and chordae forces were measured and analyzed using an incomplete counterbalanced repeated measures design with the healthy pre-prolapse valve as a control.With the exception of the edge-to-edge technique, all repair methods effectively corrected mitral regurgitation, returning regurgitant fraction to baseline levels (baseline 11.9% ± 3.7%, edge-to-edge 22.5% ± 6.9%, nonresectional remodeling 12.3% ± 3.0%, neochordal 13.4% ± 4.8%, resection 14.7% ± 5.5%, P < 0.01). Forces on the primary chordae were minimized using the neochordal and nonresectional techniques whereas the edge-to-edge and resectional techniques resulted in significantly elevated primary forces. Secondary chordae forces also followed this pattern, with edge-to-edge repair generating significantly higher secondary forces and leaflet resection trending higher than the nonresectional and neochord repairs.Although multiple methods of degenerative mitral valve repair are used clinically, their biomechanical properties vary significantly. Nonresectional techniques, including leaflet remodeling and neochordal techniques, appear to result in lower chordal forces in this ex vivo technical engineering model.

    View details for DOI 10.1016/j.xjtc.2021.09.040

    View details for PubMedID 34977730

    View details for PubMedCentralID PMC8691825

  • Ex Vivo Model of Ischemic Mitral Regurgitation and Analysis of Adjunctive Papillary Muscle Repair. Annals of biomedical engineering Imbrie-Moore, A. M., Zhu, Y., Bandy-Vizcaino, T., Park, M. H., Wilkerson, R. J., Woo, Y. J. 2021


    Ischemic mitral regurgitation (IMR) is particularly challenging to repair with lasting durability due to the complex valvular and subvalvular pathologies resulting from left ventricular dysfunction. Ex vivo simulation is uniquely suited to quantitatively analyze the repair biomechanics, but advancements are needed to model the nuanced IMR disease state. Here we present a novel IMR model featuring a dilation device with precise dilatation control that preserves annular elasticity to enable accurate ex vivo analysis of surgical repair. Coupled with augmented papillary muscle head positioning, the enhanced heart simulator system successfully modeled IMR pre- and post-surgical intervention and enabled the analysis of adjunctive subvalvular papillary muscle repair to alleviate regurgitation recurrence. The model resulted in an increase in regurgitant fraction: 11.6 ± 1.7% to 36.1 ± 4.4% (p<0.001). Adjunctive papillary muscle head fusion was analyzed relative to a simple restrictive ring annuloplasty repair and, while both repairs successfully eliminated regurgitation initially, the addition of the adjunctive subvalvular repair reduced regurgitation recurrence: 30.4 ± 5.7% vs. 12.5 ± 2.6% (p=0.002). Ultimately, this system demonstrates the success of adjunctive papillary muscle head fusion in repairing IMR as well as provides a platform to optimize surgical techniques for increased repair durability.

    View details for DOI 10.1007/s10439-021-02879-9

    View details for PubMedID 34734363

  • From hardware store to hospital: a COVID-19-inspired, cost-effective, open-source, in vivo-validated ventilator for use in resource-scarce regions. Bio-design and manufacturing Park, M. H., Zhu, Y., Wang, H., Tran, N. A., Jung, J., Paulsen, M. J., Imbrie-Moore, A. M., Baker, S., Wilkerson, R., Marin-Cuartas, M., Mullis, D. M., Woo, Y. J. 2021: 1-8


    Resource-scarce regions with serious COVID-19 outbreaks do not have enough ventilators to support critically ill patients, and these shortages are especially devastating in developing countries. To help alleviate this strain, we have designed and tested the accessible low-barrier in vivo-validated economical ventilator (ALIVE Vent), a COVID-19-inspired, cost-effective, open-source, in vivo-validated solution made from commercially available components. The ALIVE Vent operates using compressed oxygen and air to drive inspiration, while two solenoid valves ensure one-way flow and precise cycle timing. The device was functionally tested and profiled using a variable resistance and compliance artificial lung and validated in anesthetized large animals. Our functional test results revealed its effective operation under a wide variety of ventilation conditions defined by the American Association of Respiratory Care guidelines for ventilator stockpiling. The large animal test showed that our ventilator performed similarly if not better than a standard ventilator in maintaining optimal ventilation status. The FiO2, respiratory rate, inspiratory to expiratory time ratio, positive-end expiratory pressure, and peak inspiratory pressure were successfully maintained within normal, clinically validated ranges, and the animals were recovered without any complications. In regions with limited access to ventilators, the ALIVE Vent can help alleviate shortages, and we have ensured that all used materials are publicly available. While this pandemic has elucidated enormous global inequalities in healthcare, innovative, cost-effective solutions aimed at reducing socio-economic barriers, such as the ALIVE Vent, can help enable access to prompt healthcare and life saving technology on a global scale and beyond COVID-19.Supplementary Information: The online version contains supplementary material available at 10.1007/s42242-021-00164-1.

    View details for DOI 10.1007/s42242-021-00164-1

    View details for PubMedID 34567825

  • Exvivo biomechanical analysis of the Ross procedure using the modified inclusion technique in a 3-dimensionally printed left heart simulator. The Journal of thoracic and cardiovascular surgery Zhu, Y., Marin-Cuartas, M., Park, M. H., Imbrie-Moore, A. M., Wilkerson, R. J., Madira, S., Mullis, D. M., Woo, Y. J. 2021


    OBJECTIVE: The inclusion technique was developed to reinforce the pulmonary autograft to prevent dilation after the Ross procedure. Anticommissural plication (ACP), a modification technique, can reduce graft size and create neosinuses. The objective was to evaluate pulmonary valve biomechanics using the inclusion technique in the Ross procedure with and without ACP.METHODS: Seven porcine and 5 human pulmonary autografts were harvested from hearts obtained from a meat abattoir and from heart transplant recipients and donors, respectively. Five additional porcine autografts without reinforcement were used as controls. The Ross procedure was performed using the inclusion technique with a straight polyethylene terephthalate graft. The same specimens were tested both with and without ACP. Hemodynamic parameter data, echocardiography, and high-speed videography were collected via the exvivo heart simulator.RESULTS: Porcine autograft regurgitation was significantly lower after the use of inclusion technique compared with controls (P<.01). ACP compared with non-ACP in both porcine and human pulmonary autografts was associated with lower leaflet rapid opening velocity (3.9±2.4cm/sec vs 5.9±2.4cm/sec; P=.03; 3.5±0.9cm/sec vs 4.4±1.0cm/sec; P=.01), rapid closing velocity (1.9±1.6cm/sec vs 3.1±2.0cm/sec; P=.01; 1.8±0.7cm/sec vs 2.2±0.3cm/sec; P=.13), relative rapid opening force (4.6±3.0 vs 7.7±5.2; P=.03; 3.0±0.6 vs 4.0±2.1; P=.30), and relative rapid closing force (2.5±3.4 vs 5.9±2.3; P=.17; 1.4±1.3 vs 2.3±0.6; P=.25).CONCLUSIONS: The Ross procedure using the inclusion technique demonstrated excellent hemodynamic parameter results. The ACP technique was associated with more favorable leaflet biomechanics. Invivo validation should be performed to allow direct translation to clinical practice.

    View details for DOI 10.1016/j.jtcvs.2021.06.070

    View details for PubMedID 34625236