Institute Affiliations

Professional Education

  • Master of Science, Stanford University, BIOE-MS (2022)
  • PhD, Stanford University, Bioengineering
  • Residency, Stanford University, Cardiothoracic Surgery
  • MD, Cleveland Clinic Lerner College of Medicine, Medicine (2017)
  • BS, Northwestern University, Biomedical Engineering (2012)

All Publications

  • Neochordal Goldilocks: Analyzing the Biomechanics of Neochord Length on Papillary Muscle Forces Suggests Higher Tolerance to Shorter Neochordae. The Journal of thoracic and cardiovascular surgery Park, M. H., van Kampen, A., Zhu, Y., Melnitchouk, S., Levine, R. A., Borger, M. A., Woo, Y. J. 2023


    Estimating neochord lengths during mitral valve (MV) repair is challenging, as approximation must be performed largely based on intuition and surgical experience. Little data exist on quantifying the effects of neochord length misestimation. We aimed to evaluate the impact of neochord length on papillary muscle (PM) forces and MV hemodynamics, which is especially pertinent as increased forces have been linked to aberrant MV biomechanics.Porcine MVs (n=8) were mounted in an ex vivo heart simulator, and PMs were fixed to high resolution strain gauges, while hemodynamic data were recorded. We used an adjustable system to modulate neochord lengths. Optimal length was qualitatively verified by a single experienced operator, and neochordae were randomly lengthened or shortened in 1 mm increments up to ±5 mm from the optimal length.Optimal length neochordae resulted in the lowest peak composite PM forces (6.94±0.29 N), significantly different from all lengths >±1 mm. Both longer and shorter neochordae increased forces linearly according to difference from optimal length. Both peak PM forces and MR scaled more aggressively for longer versus shorter neochordae by factors of 1.6 and 6.9, respectively.Leveraging precision ex vivo heart simulation, we found that millimeter-level neochord length differences can result in significant differences in PM forces and MR, thereby altering valvular biomechanics. Differences in lengthened versus shortened neochordae scaling of forces and MR may indicate different levels of biomechanical tolerance towards longer and shorter neochordae. Our findings highlight the need for more thorough biomechanical understanding of neochordal MV repair.

    View details for DOI 10.1016/j.jtcvs.2023.04.026

    View details for PubMedID 37160219

  • Response to: Correspondence on "Has personalised surgery made another advancement in aortic root surgery?" by Zhu and Woo. Heart (British Cardiac Society) Zhu, Y., Woo, J. 2023

    View details for DOI 10.1136/heartjnl-2023-322704

    View details for PubMedID 37080763

  • The 170°/190° commissure positioning technique for bicuspid aortic valve repair using valve-sparing aortic root replacement. JTCVS techniques Zhu, Y., Woo, Y. J. 2023; 18: 37-39

    View details for DOI 10.1016/j.xjtc.2023.01.012

    View details for PubMedID 37096113

    View details for PubMedCentralID PMC10122148

  • Microfluidic encapsulation of photosynthetic cyanobacteria in hydrogel microparticles augments oxygen delivery to rescue ischemic myocardium. Journal of bioscience and bioengineering Stapleton, L. M., Farry, J. M., Zhu, Y., Lucian, H. J., Wang, H., Paulsen, M. J., Totherow, K. P., Roth, G. A., Brower, K. K., Fordyce, P. M., Appel, E. A., Woo, Y. J. 2023


    Cardiovascular disease, primarily caused by coronary artery disease, is the leading cause of death in the United States. While standard clinical interventions have improved patient outcomes, mortality rates associated with eventual heart failure still represent a clinical challenge. Macrorevascularization techniques inadequately address the microvascular perfusion deficits that persist beyond primary and secondary interventions. In this work, we investigate a photosynthetic oxygen delivery system that rescues the myocardium following acute ischemia. Using a simple microfluidic system, we encapsulated Synechococcus elongatus into alginate hydrogel microparticles (HMPs), which photosynthetically deliver oxygen to ischemic tissue in the absence of blood flow. We demonstrate that HMPs improve the viability of S. elongatus during the injection process and allow for simple oxygen diffusion. Adult male Wistar rats (n = 45) underwent sham surgery, acute ischemia reperfusion surgery, or a chronic ischemia reperfusion surgery, followed by injection of phosphate buffered saline (PBS), S. elongatus suspended in PBS, HMPs, or S. elongatus encapsulated in HMPs. Treatment with S. elongatus-HMPs mitigated cellular apoptosis and improved left ventricular function. Thus, delivery of S. elongatus encapsulated in HMPs improves clinical translation by utilizing a minimally invasive delivery platform that improves S. elongatus viability and enhances the therapeutic benefit of a novel photosynthetic system for the treatment of myocardial ischemia.

    View details for DOI 10.1016/j.jbiosc.2023.03.001

    View details for PubMedID 36966053

  • Has personalised surgery made another advancement in aortic root surgery? Heart (British Cardiac Society) Zhu, Y., Woo, J. 2023

    View details for DOI 10.1136/heartjnl-2022-322313

    View details for PubMedID 36858806

  • Trimmed central venous catheters do not increase endothelial injury in an ovine model. The journal of vascular access Wang, H., Williams, K. M., Elde, S., Bulterys, P. L., Thakore, A. D., Lucian, H. J., Farry, J. M., Mullis, D. M., Zhu, Y., Paulsen, M. J., Woo, Y. J. 2023: 11297298231153716


    Central venous catheters (CVCs) are often trimmed during heart transplantation and pediatric cardiac surgery. However, the risk of endothelial injury caused by the cut tip of the CVC has not been evaluated. We hypothesized that there is no difference in the degree of endothelial injury associated with trimmed CVCs versus standard untrimmed CVCs.In four adult male sheep, the left external jugular vein was exposed in three segments, one designated for an untouched control group, one for the trimmed CVC group, and one for the untrimmed CVC group. Trimmed and untrimmed CVC tips were rotated circumferentially within their respective segments to abrade the lumen of the vein. The vein samples were explanted, and two representative sections from each sample were analyzed using hematoxylin and eosin (H&E) staining, as well as with immunohistochemistry against CD31, von Willebrand factor (vWF), endothelial nitric oxide synthase (eNOS), and caveolin. Higher immunohistochemical stain distributions and intensities are associated with normal health and function of the venous endothelium. Data are presented as counts with percentages or as means with standard error.H&E staining revealed no evidence of endothelial injury in 6/8 (75%) samples from the untouched control group, and no injury in 4/8 (50%) samples from both the trimmed and untrimmed CVC groups (p = 0.504). In all remaining samples from each group, only mild endothelial injury was observed. Immunohistochemical analysis comparing trimmed CVCs versus untrimmed CVCs revealed no difference in the percentage of endothelial cells staining positive for CD31 (57.5% ± 7.2% vs 55.0% ± 9.2%, p = 0.982), vWF (73.8% ± 8.0% vs 62.5% ± 9.6%, p = 0.579), eNOS (66.3% ± 4.2% vs 63.8% ± 7.5%, p = 0.962), and caveolin (53.8% ± 5.0% vs 51.3% ± 4.4%, p = 0.922). There were no significant differences between the groups in the distributions of stain intensity for CD31, vWF, eNOS, and caveolin.Trimmed CVCs do not increase endothelial injury compared to standard untrimmed CVCs.

    View details for DOI 10.1177/11297298231153716

    View details for PubMedID 36765464

  • Beating heart pulmonary autograft harvest and modified inclusion technique with anti-commissural plication for the Ross procedure. JTCVS techniques Zhu, Y., Wang, H., Woo, Y. J. 2023; 17: 52-55

    View details for DOI 10.1016/j.xjtc.2022.10.009

    View details for PubMedID 36820349

    View details for PubMedCentralID PMC9938366

  • Optimization of FRESH Microspheres for Substantially Improved 3D Bioprinting Capabilities. Tissue engineering. Part C, Methods Wu, C. A., Zhu, Y., Venkatesh, A., Stark, C. J., Lee, S. H., Woo, Y. J. 2023


    Three-dimensional (3D) bioprinting demonstrates technology capable of producing structures comparable to native tissues in the human body. The Freeform Reversible Embedding of Suspended Hydrogels (FRESH) technique involves hydrogel-based bio-inks printed within a thermo-reversible support bath to provide mechanical strength to the printed construct. Smaller and more uniform microsphere sizes of FRESH were reported to aid in enhancing printing resolution and construct accuracy. Therefore, we sought to optimize the FRESH generation protocol, particularly by varying stir speed and stir duration, in hopes to further improve microsphere size and uniformity. We observed optimal conditions at a stir speed of 600 rpm and stir duration for 20 hours that generated the smallest microspheres with the best uniformity. Comparison of using the optimized FRESH to the commercial FRESH LifeSupport to bioprint single filament and geometrical constructs revealed reduced single filament diameters and higher angular precision in the optimized FRESH bio-printed constructs compared to those printed in the commercial FRESH. Overall, our refinement of the FRESH manufacturing protocol represents an important step toward enhancing 3D bioprinting resolution and construct fidelity. Improving such technologies allows for the fabrication of highly accurate constructs with anatomical properties similar to native counterparts. Such work has significant implications in the field of tissue engineering for producing accurate human organ model systems.

    View details for DOI 10.1089/ten.TEC.2022.0214

    View details for PubMedID 36719778

  • Surgical management of severe mitral annular calcification. Asian cardiovascular & thoracic annals Elde, S., Zhu, Y., MacArthur, J. W., Woo, Y. J. 2022: 2184923221136935


    BACKGROUND: Surgical management of severe mitral annular calcification (MAC) presents a challenging problem for even the most experienced surgeons. Preoperative planning is the most effective strategy to mitigate risk in these scenarios. MAC alone should not disqualify a patient from consideration for mitral valve repair, although the presence of concurrent greater than moderate stenosis warrants consideration of mitral valve replacement.METHODS: While repair and replacement techniques for mitral regurgitation in the setting of MAC overlap with those used to repair a non-calcified mitral apparatus, there are unique considerations to the surgical conduct of these procedures. Specifically, this article describes techniques that may be employed when the severity of MAC precludes typical repair or replacement strategies.RESULTS: Between 2014 and 2021, 77 patients were operated on by a single surgeon for mitral valve disease complicated by severe MAC. Using the systematic approach described herein, 1-year mortality was 7.8% and overall mortality over a follow-up period extending 1 to 8 years was 9.1%.CONCLUSIONS: Despite the inherent challenges of mitral valve repair or replacement in the setting of severe MAC, a systematic approach beginning with preoperative planning, modification of annular suture placement, and techniques to mitigate severe complications have, in our experience, resulting in a reliable methodology for managing severe MAC with excellent outcomes.

    View details for DOI 10.1177/02184923221136935

    View details for PubMedID 36537728

  • Three-Dimensional Bioprinting with Alginate by Freeform Reversible Embedding of Suspended Hydrogels with Tunable Physical Properties and Cell Proliferation. Bioengineering (Basel, Switzerland) Zhu, Y., Stark, C. J., Madira, S., Ethiraj, S., Venkatesh, A., Anilkumar, S., Jung, J., Lee, S., Wu, C. A., Walsh, S. K., Stankovich, G. A., Woo, Y. J. 2022; 9 (12)


    Extrusion-based three-dimensional (3D) bioprinting is an emerging technology that allows for rapid bio-fabrication of scaffolds with live cells. Alginate is a soft biomaterial that has been studied extensively as a bio-ink to support cell growth in 3D constructs. However, native alginate is a bio-inert material that requires modifications to allow for cell adhesion and cell growth. Cells grown in modified alginates with the RGD (arginine-glycine-aspartate) motif, a naturally existing tripeptide sequence that is crucial to cell adhesion and proliferation, demonstrate enhanced cell adhesion, spreading, and differentiation. Recently, the bioprinting technique using freeform reversible embedding of suspended hydrogels (FRESH) has revolutionized 3D bioprinting, enabling the use of soft bio-inks that would otherwise collapse in air. However, the printability of RGD-modified alginates using the FRESH technique has not been evaluated. The associated physical properties and bioactivity of 3D bio-printed alginates after RGD modification remains unclear. In this study, we characterized the physical properties, printability, and cellular proliferation of native and RGD-modified alginate after extrusion-based 3D bioprinting in FRESH. We demonstrated tunable physical properties of native and RGD-modified alginates after FRESH 3D bioprinting. Sodium alginate with RGD modification, especially at a high concentration, was associated with greatly improved cell viability and integrin clustering, which further enhanced cell proliferation.

    View details for DOI 10.3390/bioengineering9120807

    View details for PubMedID 36551013

  • Outcomes of Heart Transplantation Using a Temperature-controlled Hypothermic Storage System. Transplantation Zhu, Y., Shudo, Y., He, H., Kim, J. Y., Elde, S., Williams, K. M., Walsh, S. K., Koyano, T. K., Guenthart, B., Woo, Y. J. 2022


    The SherpaPak Cardiac Transport System is a novel technology that provides stable, optimal hypothermic control during organ transport. The objectives of this study were to describe our experience using the SherpaPak system and to compare outcomes after heart transplantation after using SherpaPak versus the conventional static cold storage method (non-SherpaPak).From 2018 to June 2021, 62 SherpaPak and 186 non-SherpaPak patients underwent primary heart transplantation at Stanford University with follow-up through May 2022. The primary end point was all-cause mortality, and secondary end points were postoperative complications. Optimal variable ratio matching, cox proportional hazards regression model, and Kaplan-Meier survival analyses were performed.Before matching, the SherpaPak versus non-SherpaPak patients were older and received organs with significantly longer total allograft ischemic time. After matching, SherpaPak patients required fewer units of blood product for perioperative transfusion compared with non-SherpaPak patients but otherwise had similar postoperative outcomes such as hospital length of stay, primary graft dysfunction, inotrope score, mechanical circulatory support use, cerebral vascular accident, myocardial infarction, respiratory failure, new renal failure requiring dialysis, postoperative bleeding or tamponade requiring reoperation, infection, and survival.In conclusion, this is one of the first retrospective comparison studies that evaluated the outcomes of heart transplantation using organs preserved and transported via the SherpaPak system. Given the excellent outcomes, despite prolonged total allograft ischemic time, it may be reasonable to adopt the SherpaPak system to accept organs from a remote location to further expand the donor pool.

    View details for DOI 10.1097/TP.0000000000004416

    View details for PubMedID 36510359

  • 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

  • Resection of a synovial cell sarcoma by cardiac autotransplantation: A case report. JTCVS techniques Mullis, D. M., Zhu, Y., Guenthart, B. A., Bonham, S. A., Trope, W. L., Berry, G. J., Woo, Y. J., MacArthur, J. W. 2022; 16: 123-127

    View details for DOI 10.1016/j.xjtc.2022.09.009

    View details for PubMedID 36510550

    View details for PubMedCentralID PMC9735421

  • 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

  • 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

  • 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

  • A novel photosynthetic biologic topical gel for enhanced localized hyperoxygenation augments wound healing in peripheral artery disease. Scientific reports Zhu, Y., Jung, J., Anilkumar, S., Ethiraj, S., Madira, S., Tran, N. A., Mullis, D. M., Casey, K. M., Walsh, S. K., Stark, C. J., Venkatesh, A., Boakye, A., Wang, H., Woo, Y. J. 2022; 12 (1): 10028


    Peripheral artery disease and the associated ischemic wounds are substantial causes of global morbidity and mortality, affecting over 200 million people worldwide. Although advancements have been made in preventive, pharmacologic, and surgical strategies to treat this disease, ischemic wounds, a consequence of end-stage peripheral artery disease, remain a significant clinical and economic challenge. Synechococcus elongatus is a cyanobacterium that grows photoautotrophically and converts carbon dioxide and water into oxygen. We present a novel topical biologic gel containing S. elongatus that provides oxygen via photosynthesis to augment wound healing by rescuing ischemic tissues caused by peripheral artery disease. By using light rather than blood as a source of energy, our novel topical therapy significantly accelerated wound healing in two rodent ischemic wound models. This novel topical gel can be directly translated to clinical practice by using a localized, portable light source without interfering with patients' daily activities, demonstrating potential to generate a paradigm shift in treating ischemic wounds from peripheral artery disease. Its novelty, low production cost, and ease of clinical translatability can potentially impact the clinical care for millions of patients suffering from peripheral arterial disease.

    View details for DOI 10.1038/s41598-022-14085-1

    View details for PubMedID 35705660

  • FDA Emergency Use Authorization-Approved Novel Coronavirus Disease 2019, Pressure-Regulated, Mechanical Ventilator Splitter That Enables Differential Compliance Multiplexing. ASAIO journal (American Society for Artificial Internal Organs : 1992) Paulsen, M. J., Zhu, Y., Park, M. H., Imbrie-Moore, A. M., Baker, S., Walter Edmonston, D., Dawson, T., Ly, E., Martin Bell, S., Tran, N. A., Jung, J., Cedarleaf-Pavy, J., Sridhar, K. R., Venkataraman, V., Woo, Y. J. 2022


    Infection with the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may cause viral pneumonia and acute respiratory distress syndrome (ARDS). Treatment of ARDS often requires mechanical ventilation and may take weeks for resolution. In areas with a large outbreaks, there may be shortages of ventilators available. While rudimentary methods for ventilator splitting have been described, given the range of independent ventilatory settings required for each patient, this solution is suboptimal. Here, we describe a device that can split a ventilator among up to four patients while allowing for individualized settings. The device has been validated in vitro and in vivo.

    View details for DOI 10.1097/MAT.0000000000001756

    View details for PubMedID 35667305

  • 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

  • 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

  • A Novel Device for Intraoperative Direct Visualization of a Pressurized Root in Aortic Valve Repair. The Annals of thoracic surgery Zhu, Y., Imbrie-Moore, A. M., Paulsen, M. J., Park, M. H., Tran, N. A., Woo, Y. J. 2022


    PURPOSE: One major challenge in generating reproducible aortic valve (AV) repair results is the inability to assess AV morphology under physiologic pressure. A transparent intraoperative aortic valve visualization device was designed and manufactured.DESCRIPTION: This device is comprised of an open proximal end, a cantilevered edge to allow attachment of the device to the aorta or graft, a distal viewing surface, and two side ports for fluid delivery and air removal.EVALUATION: The performance of the device was evaluated ex vivo using normal porcine AV in situ (n=3), AV after valve-sparing aortic root replacement (VSARR, n=3), and porcine pulmonary valve in Ross procedure (n=3), and in 3 patients who underwent VSARR. AV morphology was clearly visualized using the device in all experiments. In human, the use of this device successfully illustrated cusp prolapse after the initial VSARR and effectively guided additional cusp repair.CONCLUSIONS: This device successfully allows for direct visual assessment of the AV apparatus under physiologic pressure. The use of this device can potentially increase the adoptability of AV repair in clinical practice.

    View details for DOI 10.1016/j.athoracsur.2022.02.013

    View details for PubMedID 35216987

  • 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

  • Natural cardiac regeneration conserves native biaxial left ventricular biomechanics after myocardial infarction in neonatal rats. Journal of the mechanical behavior of biomedical materials Wang, H., Wisneski, A., Imbrie-Moore, A. M., Paulsen, M. J., Wang, Z., Xuan, Y., Lopez Hernandez, H., Hironaka, C. E., Lucian, H. J., Shin, H. S., Anilkumar, S., Thakore, A. D., Farry, J. M., Eskandari, A., Williams, K. M., Grady, F., Wu, M. A., Jung, J., Stapleton, L. M., Steele, A. N., Zhu, Y., Woo, Y. J. 1800; 126: 105074


    After myocardial infarction (MI), adult mammals exhibit scar formation, adverse left ventricular (LV) remodeling, LV stiffening, and impaired contractility, ultimately resulting in heart failure. Neonatal mammals, however, are capable of natural heart regeneration after MI. We hypothesized that neonatal cardiac regeneration conserves native biaxial LV mechanics after MI. Wistar rat neonates (1 day old, n=46) and adults (8-10 weeks old, n=20) underwent sham surgery or permanent left anterior descending coronary artery ligation. At 6 weeks after neonatal MI, Masson's trichrome staining revealed negligible fibrosis. Echocardiography for the neonatal MI (n=15) and sham rats (n=14) revealed no differences in LV wall thickness or chamber diameter, and both groups had normal ejection fraction (72.7% vs 77.5%, respectively, p=0.1946). Biaxial tensile testing revealed similar stress-strain curves along both the circumferential and longitudinal axes across a full range of physiologic stresses and strains. The circumferential modulus (267.9kPa vs 274.2kPa, p=0.7847), longitudinal modulus (269.3kPa vs 277.1kPa, p=0.7435), and maximum shear stress (3.30kPa vs 3.95kPa, p=0.5418) did not differ significantly between the neonatal MI and sham groups, respectively. In contrast, transmural scars were observed at 4 weeks after adult MI. Adult MI hearts (n=7) exhibited profound LV wall thinning (p<0.0001), chamber dilation (p=0.0246), and LV dysfunction (ejection fraction 45.4% vs 79.7%, p<0.0001) compared to adult sham hearts (n=7). Adult MI hearts were significantly stiffer than adult sham hearts in both the circumferential (321.5kPa vs 180.0kPa, p=0.0111) and longitudinal axes (315.4kPa vs 172.3kPa, p=0.0173), and also exhibited greater maximum shear stress (14.87kPa vs 3.23kPa, p=0.0162). Our study is the first to show that native biaxial LV mechanics are conserved after neonatal heart regeneration following MI, thus adding biomechanical support for the therapeutic potential of cardiac regeneration in the treatment of ischemic heart disease.

    View details for DOI 10.1016/j.jmbbm.2022.105074

    View details for PubMedID 35030471

  • Electrophysiologic Conservation of Epicardial Conduction Dynamics After Myocardial Infarction and Natural Heart Regeneration in Newborn Piglets. Frontiers in cardiovascular medicine Wang, H., Pong, T., Obafemi, O. O., Lucian, H. J., Aparicio-Valenzuela, J., Tran, N. A., Mullis, D. M., Elde, S., Tada, Y., Baker, S. W., Wang, C. Y., Cyr, K. J., Paulsen, M. J., Zhu, Y., Lee, A. M., Woo, Y. J. 2022; 9: 829546


    Newborn mammals, including piglets, exhibit natural heart regeneration after myocardial infarction (MI) on postnatal day 1 (P1), but this ability is lost by postnatal day 7 (P7). The electrophysiologic properties of this naturally regenerated myocardium have not been examined. We hypothesized that epicardial conduction is preserved after P1 MI in piglets. Yorkshire-Landrace piglets underwent left anterior descending coronary artery ligation at age P1 (n = 6) or P7 (n = 7), After 7 weeks, cardiac magnetic resonance imaging was performed with late gadolinium enhancement for analysis of fibrosis. Epicardial conduction mapping was performed using custom 3D-printed high-resolution mapping arrays. Age- and weight-matched healthy pigs served as controls (n = 6). At the study endpoint, left ventricular (LV) ejection fraction was similar for controls and P1 pigs (46.4 ± 3.0% vs. 40.3 ± 4.9%, p = 0.132), but significantly depressed for P7 pigs (30.2 ± 6.6%, p < 0.001 vs. control). The percentage of LV myocardial volume consisting of fibrotic scar was 1.0 ± 0.4% in controls, 9.9 ± 4.4% in P1 pigs (p = 0.002 vs. control), and 17.3 ± 4.6% in P7 pigs (p < 0.001 vs. control, p = 0.007 vs. P1). Isochrone activation maps and apex activation time were similar between controls and P1 pigs (9.4 ± 1.6 vs. 7.8 ± 0.9 ms, p = 0.649), but significantly prolonged in P7 pigs (21.3 ± 5.1 ms, p < 0.001 vs. control, p < 0.001 vs. P1). Conduction velocity was similar between controls and P1 pigs (1.0 ± 0.2 vs. 1.1 ± 0.4 mm/ms, p = 0.852), but slower in P7 pigs (0.7 ± 0.2 mm/ms, p = 0.129 vs. control, p = 0.052 vs. P1). Overall, our data suggest that epicardial conduction dynamics are conserved in the setting of natural heart regeneration in piglets after P1 MI.

    View details for DOI 10.3389/fcvm.2022.829546

    View details for PubMedID 35355973

  • Post-Transplant Extracorporeal Membrane Oxygenation for Severe Primary Graft Dysfunction to Support the Use of Marginal Donor Hearts. Transplant international : official journal of the European Society for Organ Transplantation Shudo, Y., Alassar, A., Wang, H., Lingala, B., He, H., Zhu, Y., Hiesinger, W., MacArthur, J. W., Boyd, J. H., Lee, A. M., Currie, M., Woo, Y. J. 2022; 35: 10176


    Severe primary graft dysfunction (PGD) is the leading cause of early postoperative mortality following orthotopic heart transplantation (OHT). Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been used as salvage therapy. This study aimed to evaluate the outcomes in adult OHT recipients who underwent VA-ECMO for severe PGD. We retrospectively reviewed 899 adult (≥18years) patients who underwent primary OHT at our institution between 1997 and 2017. Recipients treated with VA-ECMO (19, 2.1%) exhibited a higher incidence of previous cardiac surgery (p = .0220), chronic obstructive pulmonary disease (p = .0352), and treatment with a calcium channel blocker (p = .0018) and amiodarone (p = .0148). Cardiopulmonary bypass (p = .0410) and aortic cross-clamp times (p = .0477) were longer in the VA-ECMO cohort and they were more likely to have received postoperative transfusion (p = .0013); intra-aortic balloon pump (IABP, p < .0001), and reoperation for bleeding or tamponade (p < .0001). The 30-day, 1-year, and overall survival after transplantation of non-ECMO patients were 95.9, 88.8, and 67.4%, respectively, compared to 73.7, 57.9, and 47.4%, respectively in the ECMO cohort. Fourteen (73.7%) of the ECMO patients were weaned after a median of 7days following OHT (range: 1-12days). Following OHT, VA-ECMO may be a useful salvage therapy for severe PGD and can potentially support the usage of marginal donor hearts.

    View details for DOI 10.3389/ti.2022.10176

    View details for PubMedID 35340846

  • 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

  • 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., Imbrie-Moore, A., Wang, H., Wilkerson, R., Farry, J., Zhu, Y., Ma, M., MacArthur, J. W., Woo, Y. 2021; 10: 244-251
  • 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

  • Videographic conceptual dynamic representation of bicuspid aortic valve anatomic configurations and structural inter-relationships. JTCVS techniques Woo, Y. J., Paulsen, M. J., de Kerchove, L., Zhu, Y. 2021; 9: 44-45

    View details for DOI 10.1016/j.xjtc.2021.06.019

    View details for PubMedID 34647056

  • 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

  • Graft Type and Routing for Repair of Aortoesophageal Fistula ANNALS OF THORACIC SURGERY Zhu, Y., Lee, A. M. 2021; 112 (3): 1033-1034
  • A neonatal leporine model of age-dependent natural heart regeneration after myocardial infarction. The Journal of thoracic and cardiovascular surgery Wang, H., Hironaka, C. E., Mullis, D. M., Lucian, H. J., Shin, H. S., Tran, N. A., Thakore, A. D., Anilkumar, S., Wu, M. A., Paulsen, M. J., Zhu, Y., Baker, S. W., Woo, Y. J. 2021


    OBJECTIVES: Neonatal rodents and piglets naturally regenerate the injured heart after myocardial infarction. We hypothesized that neonatal rabbits also exhibit natural heart regeneration after myocardial infarction.METHODS: New Zealand white rabbit kits underwent sham surgery or left coronary ligation on postnatal day 1 (n=94), postnatal day 4 (n=11), or postnatal day 7 (n=52). Hearts were explanted 1day postsurgery to confirm ischemic injury, at 1week postsurgery to assess cardiomyocyte proliferation, and at 3weeks postsurgery to assess left ventricular ejection fraction and scar size. Data are presented as mean±standard deviation.RESULTS: Size of ischemic injury as a percentage of left ventricular area was similar after myocardial infarction on postnatal day 1 versus on postnatal day 7 (42.3%±5.4% vs 42.3%±4.7%, P=.9984). Echocardiography confirmed severely reduced ejection fraction at 1day after postnatal day 1 myocardial infarction (33.7%±5.3% vs 65.2%±5.5% for postnatal day 1 sham, P=.0001), but no difference at 3weeks after postnatal day 1 myocardial infarction (56.0%±4.0% vs 58.0%±3.3% for postnatal day 1 sham, P=.2198). Ejection fraction failed to recover after postnatal day 4 myocardial infarction (49.2%±1.8% vs 58.5%±5.8% for postnatal day 4 sham, P=.0109) and postnatal day 7 myocardial infarction (39.0%±7.8% vs 60.2%±5.0% for postnatal day 7 sham, P<.0001). At 3weeks after infarction, fibrotic scar represented 5.3%±1.9%, 14.3%±4.9%, and 25.4%±13.3% of the left ventricle area in the postnatal day 1, postnatal day 4, and postnatal day 7 groups, respectively. An increased proportion of peri-infarct cardiomyocytes expressed Ki67 (15.9%±1.8% vs 10.2%±0.8%, P=.0039) and aurora B kinase (4.0%±0.9% vs 1.5%±0.6%, P=.0088) after postnatal day 1 myocardial infarction compared with sham, but no increase was observed after postnatal day 7 myocardial infarction.CONCLUSIONS: A neonatal leporine myocardial infarction model reveals that newborn rabbits are capable of age-dependent natural heart regeneration.

    View details for DOI 10.1016/j.jtcvs.2021.08.013

    View details for PubMedID 34649718

  • The Stanford experience of heart transplantation over five decades. European heart journal Zhu, Y., Lingala, B., Baiocchi, M., Toro Arana, V., Williams, K. M., Shudo, Y., Oyer, P. E., Woo, Y. J. 2021


    AIMS: Since 1968, heart transplantation has become the definitive treatment for patients with end-stage heart failure. We aimed to summarize our experience in heart transplantation at Stanford University since the first transplantation performed over 50years ago.METHODS AND RESULTS: From 6 January 1968 to 30 November 2020, 2671 patients presented to Stanford University for heart transplantation, of which 1958 were adult heart transplantations. Descriptive analyses were performed for patients in 1968-95 (n=639). Stabilized inverse probability weighting was applied to compare patients in 1996-2006 (n=356) vs. 2007-19 (n=515). Follow-up data were updated through 2020. The primary endpoint was all-cause mortality. Prior to weighting, recipients in 2007-19 vs. those in 1996-2006 were older and had heavier burden of chronic diseases. After the application of stabilized inverse probability weighting, the distance organ travelled increased from 84.2±111.1 miles to 159.3±169.9 miles from 1996-2006 to 2007-19. Total allograft ischaemia time also increased over time (199.6±52.7 vs. 225.3±50.0min). Patients in 2007-19 showed superior survival than those in 1996-2006 with a median survival of 12.1 vs. 11.1years.CONCLUSION: In this half-century retrospective descriptive study from one of the largest heart transplant programmes in the USA, long-term survival after heart transplantation has improved over time despite increased recipient and donor age, worsening comorbidities, increased technical complexity, and prolonged total allograft ischaemia time. Further investigation is warranted to delineate factors associated with the excellent outcomes observed in this study.

    View details for DOI 10.1093/eurheartj/ehab416

    View details for PubMedID 34333595

  • Cusp repair techniques in bicuspid and tricuspid aortic valves. JTCVS techniques Zhu, Y., Woo, Y. J. 2021; 7: 109-116

    View details for DOI 10.1016/j.xjtc.2021.01.029

    View details for PubMedID 34318219

    View details for PubMedCentralID PMC8311607

  • Cusp repair techniques in bicuspid and tricuspid aortic valves JTCVS TECHNIQUES Zhu, Y., Woo, Y. 2021; 7: 109-116
  • Extracorporeal Membrane Oxygenation Bridge to Heart-Lung Transplantation. ASAIO journal (American Society for Artificial Internal Organs : 1992) Shudo, Y., Elde, S., Lingala, B., He, H., Casselman, K. G., Zhu, Y., Kasinpila, P., Woo, Y. J. 2021

    View details for DOI 10.1097/MAT.0000000000001457

    View details for PubMedID 34843181

  • The impact of donor sex on heart transplantation outcomes-a study of over 60,000 patients in the United States. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Zhu, Y., Shudo, Y., Lingala, B., Joseph Woo, Y. 2021


    BACKGROUND: The impact of donor sex on heart transplantation outcomes irrespective of recipient sex remains unclear. The objective of this study was to evaluate the impact of donor sex on heart transplantation outcomes in the United States.METHODS: From 1987 to March 2019, 63,775 adult patients who underwent heart transplantation were matched to 27,509 male and 11,474 female donors in the United States. Data were prospectively collected by the United Network for Organ Sharing (UNOS). Patients without missing data were stratified by donor sex and donor menopause status. The groups were matched 1:1 using the propensity score of each patient. Kaplan-Meier survival and cox proportional hazards regression analyses were performed. The primary endpoint was all-cause mortality. Secondary endpoints were postoperative complications.RESULTS: Propensity matching generated 15,506 and 1,094 patients based on donor sex and menopause status, respectively. Recipients who received female donor allografts were more likely to have acute rejection episodes requiring anti-rejection medical treatment (11.9% vs 10.1%, p=.007) and require post-transplant dialysis (10.9% vs 9.3%, p = .001) than those who received male donor allografts. Overall survival using female vs male donor allografts was similar (p=.34). Recipients who received pre- vs post-menopausal female donor hearts had similar postoperative outcomes and overall survival (p=.23).CONCLUSIONS: Analysis of the UNOS database showed similar median survival using female vs male donor hearts in adult heart transplantation, irrespective of donor menopause status. Female donor allografts are used far less frequently, thus these results represent an opportunity to maximize usage by better utilization of suitable female donor organs.

    View details for DOI 10.1016/j.healun.2021.04.016

    View details for PubMedID 34083118

  • Graft Type and Routing for Repair of Aortoesophageal Fistula. The Annals of thoracic surgery Zhu, Y., Lee, A. M. 2021

    View details for DOI 10.1016/j.athoracsur.2021.01.062

    View details for PubMedID 33631152

  • Heart Valve Biomechanics: The Frontiers of Modeling Modalities and the Expansive Capabilities of Ex Vivo Heart Simulation. Frontiers in cardiovascular medicine Park, M. H., Zhu, Y., Imbrie-Moore, A. M., Wang, H., Marin-Cuartas, M., Paulsen, M. J., Woo, Y. J. 2021; 8: 673689


    The field of heart valve biomechanics is a rapidly expanding, highly clinically relevant area of research. While most valvular pathologies are rooted in biomechanical changes, the technologies for studying these pathologies and identifying treatments have largely been limited. Nonetheless, significant advancements are underway to better understand the biomechanics of heart valves, pathologies, and interventional therapeutics, and these advancements have largely been driven by crucial in silico, ex vivo, and in vivo modeling technologies. These modalities represent cutting-edge abilities for generating novel insights regarding native, disease, and repair physiologies, and each has unique advantages and limitations for advancing study in this field. In particular, novel ex vivo modeling technologies represent an especially promising class of translatable research that leverages the advantages from both in silico and in vivo modeling to provide deep quantitative and qualitative insights on valvular biomechanics. The frontiers of this work are being discovered by innovative research groups that have used creative, interdisciplinary approaches toward recapitulating in vivo physiology, changing the landscape of clinical understanding and practice for cardiovascular surgery and medicine.

    View details for DOI 10.3389/fcvm.2021.673689

    View details for PubMedID 34307492

  • Photosynthetic symbiotic therapeutics - An innovative, effective treatment for ischemic cardiovascular diseases. Journal of molecular and cellular cardiology Zhu, Y., Woo, Y. J. 2021


    Ischemic heart disease is a major cause of global morbidity and mortality, affecting over 15 million patients in the United States. Recent advances in research and innovation have greatly broadened clinicians' ability to treatment ischemic heart disease and associated heart failure using various preventive, pharmacologic, and surgical strategies. Specifically, innovative photosynthetic symbiotic systems using Synechococcus elongatus has gained significant attention. S. elongatus is a unicellular cyanobacterium that can carry out oxygenic photosynthesis. Photosynthetic therapies have been developed to rescue ischemic tissue by taking up tissue-derived carbon dioxide and in turn releasing oxygen for sustained aerobic metabolism during ischemia. In this article, we review the application of cyanobacteria, specifically S. elongatus, in the field of biotechnology, ischemic heart disease, and other clinical applications in ischemic diseases. We also address the motivation for innovation and current limitations in the field of S. elongatus photosynthetic therapeutics for ischemic cardiovascular disease interventions.

    View details for DOI 10.1016/j.yjmcc.2021.11.007

    View details for PubMedID 34813842

  • Electrophysiologic Conservation of Epicardial Conduction Dynamics After Myocardial Infarction in Newborn Piglets Wang, H., Pong, T., Lucian, H., Aparicio-Valenzuela, J., Tada, Y., Sakhamuri, S., Baker, S. W., Tran, N. A., Paulsen, M. J., Zhu, Y., Lee, A. M., Woo, Y. LIPPINCOTT WILLIAMS & WILKINS. 2020
  • Collagen-Supplemented Incubation Rapidly Augments Mechanical Property of Fibroblast Cell Sheets. Tissue engineering. Part A Zhu, Y., Thakore, A. D., Farry, J. M., Jung, J., Anilkumar, S., Wang, H., Imbrie-Moore, A. M., Park, M. H., Tran, N. A., Woo, Y. J. 2020


    Cell sheet technology using UpCell plates is a modern tool that enables the rapid creation of a single-layered cells without using extracellular matrix enzymatic digestion. Although this technique has the advantage of maintaining a sheet of cells without needing artificial scaffolds, these cell sheets remain extremely fragile. Collagen, the most abundant extracellular matrix component, is an attractive candidate for modulating tissue mechanical properties given its tunable property. In this study, we demonstrated rapid mechanical property augmentation of human dermal fibroblast cell sheets after incubation with bovine type I collagen for 24 hours on UpCell plates. We showed that treatment with collagen resulted in increased collagen I incorporation within the cell sheet without affecting cell morphology, cell type, or cell sheet quality. Atomic force microscopy measurements for controls, and cell sheets that received 50g/mL and 100g/mL collagen I treatments revealed an average Young's modulus of their respective intercellular regions: 6.6±1.0, 14.4±6.6, and 19.8±3.8 kPa during the loading condition, and 10.3±4.7, 11.7±2.2, and 18.1±3.4 kPa during the unloading condition. This methodology of rapid mechanical property augmentation of a cell sheet has a potential impact on cell sheet technology by improving the ease of construct manipulation, enabling new translational tissue engineering applications.

    View details for DOI 10.1089/ten.TEA.2020.0128

    View details for PubMedID 32703108

  • Ex Vivo Analysis of a Porcine Bicuspid Aortic Valve and Aneurysm Disease Model. The Annals of thoracic surgery Zhu, Y., Imbrie-Moore, A. M., Park, M. H., Paulsen, M. J., Wang, H., MacArthur, J. W., Woo, Y. J. 2020


    We identified an extremely rare congenital porcine type 0 lateral bicuspid aortic valve (BAV) from a fresh porcine heart. Using a 3D-printed ex vivo left heart simulator, we analyzed valvular hemodynamics at baseline, in an aortic aneurysm disease model, and after valve-sparing root replacement (VSRR). We showed that BAV regurgitation due to aortic aneurysm can be successfully repaired without significant hemodynamic impairment with the VSRR technique in an individualized approach. Our results provide direct hemodynamic evidence supporting the use of VSRR for patients with BAV regurgitation.

    View details for DOI 10.1016/j.athoracsur.2020.05.086

    View details for PubMedID 32663472

  • Novel bicuspid aortic valve model with aortic regurgitation for hemodynamic status analysis using an exvivo simulator. The Journal of thoracic and cardiovascular surgery Zhu, Y., Imbrie-Moore, A. M., Paulsen, M. J., Priromprintr, B., Wang, H., Lucian, H. J., Farry, J. M., Woo, Y. J. 2020


    OBJECTIVE: The objective was to design and evaluate a clinically relevant, novel exvivo bicuspid aortic valve model that mimics the most common human phenotype with associated aortic regurgitation.METHODS: Three bovine aortic valves were mounted asymmetrically in a previously validated 3-dimensional-printed left heart simulator. The non-right commissure and the non-left commissure were both shifted slightly toward the left-right commissure, and the left and right coronary cusps were sewn together. The left-right commissure was then detached and reimplanted 10mm lower than its native height. Free margin shortening was used for valve repair. Hemodynamic status, high-speed videography, and echocardiography data were collected before and after the repair.RESULTS: The bicuspid aortic valve model was successfully produced and repaired. High-speed videography confirmed prolapse of the fused cusp of the baseline bicuspid aortic valve models in diastole. Hemodynamic and pressure data confirmed accurate simulation of diseased conditions with aortic regurgitation and the subsequent repair. Regurgitant fraction postrepair was significantly reduced compared with that at baseline (14.5 ± 4.4% vs 28.6%±3.4%; P=.037). There was no change in peak velocity, peak gradient, or mean gradient across the valve pre- versus postrepair: 293.3±18.3cm/sec versus 325.3±58.2cm/sec (P=.29), 34.3±4.2mm Hg versus 43.3±15.4mm Hg (P=.30), and 11±1mm Hg versus 9.3±2.5mm Hg (P=.34), respectively.CONCLUSIONS: An exvivo bicuspid aortic valve model was designed that recapitulated the most common human phenotype with aortic regurgitation. These valves were successfully repaired, validating its potential for evaluating valve hemodynamics and optimizing surgical repair for bicuspid aortic valves.

    View details for DOI 10.1016/j.jtcvs.2020.06.028

    View details for PubMedID 32747120

  • Bilateral vs. Single Internal Mammary Artery Grafts for Coronary Artery Bypass in the United States. The Annals of thoracic surgery Zhu, Y., Lingala, B., Wang, H., Woo, Y. J. 2020


    BACKGROUND: The use of bilateral internal mammary arteries (BIMA) in coronary artery bypass grafting remains controversial. The objective of this study was to investigate the long-term outcomes using BIMA versus single internal mammary artery (SIMA) in the United States.METHODS: Medicare beneficiaries who underwent primary isolated coronary artery bypass surgery using SIMA or BIMA from 1999 to 2010 were included in this retrospective study, with follow up through 2014. Greedy matching algorithms were used for 1:4 matching on propensity score based on age, gender, year of surgery, and comorbidities. Kaplan-Meier survival analyses were performed. The primary outcome was death from any cause.RESULTS: A total of 1,156,339 and 25,005 patients aged 72±7.6 and 70.3±7.9 years-old underwent primary isolated coronary artery bypass surgery using SIMA and BIMA, respectively. Matching created comparable groups with 95,780 SIMA and 24,160 BIMA patients. Matched median survival using SIMA was 11.8 versus 12.4 years using BIMA (p<.0001). At ten years of follow up, the respective survival rates of using SIMA versus BIMA were 58.3% versus 61.1%, respectively. The stratified matched median survival using SIMA versus BIMA with one, two, three, and four or more aortocoronary bypasses were 11.8 versus 12.3 years (p=.005), 11.7 versus 12.5 years (p<.0001), 11.9 versus 12.3 years (p=.01), and 11.4 versus 12 years (p=.02), respectively.CONCLUSIONS: Primary isolated coronary artery bypass surgery using BIMA rather than SIMA was associated with improved long-term survival. This survival advantage was independent of aortocoronary bypass grafts or patient diabetes status.

    View details for DOI 10.1016/j.athoracsur.2020.05.049

    View details for PubMedID 32599051

  • Multiaxial Lenticular Stress-Strain Relationship of Native Myocardium is Preserved by Infarct-Induced Natural Heart Regeneration in Neonatal Mice. Scientific reports Wang, H., Bennett-Kennett, R., Paulsen, M. J., Hironaka, C. E., Thakore, A. D., Farry, J. M., Eskandari, A., Lucian, H. J., Shin, H. S., Wu, M. A., Imbrie-Moore, A. M., Steele, A. N., Stapleton, L. M., Zhu, Y., Dauskardt, R. H., Woo, Y. J. 2020; 10 (1): 7319


    Neonatal mice exhibit natural heart regeneration after myocardial infarction (MI) on postnatal day 1 (P1), but this ability is lost by postnatal day 7 (P7). Cardiac biomechanics intricately affect long-term heart function, but whether regenerated cardiac muscle is biomechanically similar to native myocardium remains unknown. We hypothesized that neonatal heart regeneration preserves native left ventricular (LV) biomechanical properties after MI. C57BL/6J mice underwent sham surgery or left anterior descending coronary artery ligation at age P1 or P7. Echocardiography performed 4 weeks post-MI showed that P1 MI and sham mice (n=22, each) had similar LV wall thickness, diameter, and ejection fraction (59.6% vs 60.7%, p=0.6514). Compared to P7 shams (n=20), P7 MI mice (n=20) had significant LV wall thinning, chamber enlargement, and depressed ejection fraction (32.6% vs 61.8%, p<0.0001). Afterward, the LV was explanted and pressurized ex vivo, and the multiaxial lenticular stress-strain relationship was tracked. While LV tissue modulus for P1 MI and sham mice were similar (341.9 kPa vs 363.4 kPa, p=0.6140), the modulus for P7 MI mice was significantly greater than that for P7 shams (691.6 kPa vs 429.2 kPa, p=0.0194). We conclude that, in neonatal mice, regenerated LV muscle has similar biomechanical properties as native LV myocardium.

    View details for DOI 10.1038/s41598-020-63324-w

    View details for PubMedID 32355240

  • A novel cross-species model of Barlow's disease to biomechanically analyze repair techniques in an exvivo left heart simulator. The Journal of thoracic and cardiovascular surgery Imbrie-Moore, A. M., Paulsen, M. J., Zhu, Y., Wang, H., Lucian, H. J., Farry, J. M., MacArthur, J. W., Ma, M., Woo, Y. J. 2020


    OBJECTIVE: Barlow's disease remains challenging to repair, given the complex valvular morphology and lack of quantitative data to compare techniques. Although there have been recent strides in exvivo evaluation of cardiac mechanics, to our knowledge, there is no disease model that accurately simulates the morphology and pathophysiology of Barlow's disease. The purpose of this study was to design such a model.METHODS: To simulate Barlow's disease, a cross-species exvivo model was developed. Bovine mitral valves (n=4) were sewn into a porcine annulus mount to create excess leaflet tissue and elongated chordae. A heart simulator generated physiologic conditions while hemodynamic data, high-speed videography, and chordal force measurements were collected. The regurgitant valves were repaired using nonresectional repair techniques such as neochord placement.RESULTS: The model successfully imitated the complexities of Barlow's disease, including redundant, billowing bileaflet tissues with notable regurgitation. After repair, hemodynamic data confirmed reduction of mitral leakage volume (25.9±2.9 vs 2.1±1.8mL, P<.001) and strain gauge analysis revealed lower primary chordae forces (0.51±0.17 vs 0.10±0.05N, P<.001). In addition, the maximum rate of change of force was significantly lower postrepair for both primary (30.80±11.38 vs 8.59±4.83N/s, P<.001) and secondary chordae (33.52±10.59 vs 19.07±7.00N/s, P=.006).CONCLUSIONS: This study provides insight into the biomechanics of Barlow's disease, including sharply fluctuating force profiles experienced by elongated chordae prerepair, as well as restoration of primary chordae forces postrepair. Our disease model facilitates further in-depth analyses to optimize the repair of Barlow's disease.

    View details for DOI 10.1016/j.jtcvs.2020.01.086

    View details for PubMedID 32249088

  • Natural Heart Regeneration in a Neonatal Rat Myocardial Infarction Model. Cells Wang, H., Paulsen, M. J., Hironaka, C. E., Shin, H. S., Farry, J. M., Thakore, A. D., Jung, J., Lucian, H. J., Eskandari, A., Anilkumar, S., Wu, M. A., Cabatu, M. C., Steele, A. N., Stapleton, L. M., Zhu, Y., Woo, Y. J. 2020; 9 (1)


    Newborn mice and piglets exhibit natural heart regeneration after myocardial infarction (MI). Discovering other mammals with this ability would provide evidence that neonatal cardiac regeneration after MI may be a conserved phenotype, which if activated in adults could open new options for treating ischemic cardiomyopathy in humans. Here, we hypothesized that newborn rats undergo natural heart regeneration after MI. Using a neonatal rat MI model, we performed left anterior descending coronary artery ligation or sham surgery in one-day-old rats under hypothermic circulatory arrest (n = 74). Operative survival was 97.3%. At 1 day post-surgery, rats in the MI group exhibited significantly reduced ejection fraction (EF) compared to shams (87.1% vs. 53.0%, p < 0.0001). At 3 weeks post-surgery, rats in the sham and MI groups demonstrated no difference in EF (71.1% vs. 69.2%, respectively, p = 0.2511), left ventricular wall thickness (p = 0.9458), or chamber diameter (p = 0.7801). Masson's trichome and picrosirius red staining revealed minimal collagen scar after MI. Increased numbers of cardiomyocytes positive for 5-ethynyl-2'-deoxyuridine (p = 0.0072), Ki-67 (p = 0.0340), and aurora B kinase (p = 0.0430) were observed within the peri-infarct region after MI, indicating ischemia-induced cardiomyocyte proliferation. Overall, we present a neonatal rat MI model and demonstrate that newborn rats are capable of endogenous neocardiomyogenesis after MI.

    View details for DOI 10.3390/cells9010229

    View details for PubMedID 31963369

  • Type A Aortic Dissection-Experience Over 5 Decades: JACC Historical Breakthroughs in Perspective. Journal of the American College of Cardiology Zhu, Y. n., Lingala, B. n., Baiocchi, M. n., Tao, J. J., Toro Arana, V. n., Khoo, J. W., Williams, K. M., Traboulsi, A. A., Hammond, H. C., Lee, A. M., Hiesinger, W. n., Boyd, J. n., Oyer, P. E., Stinson, E. B., Reitz, B. A., Mitchell, R. S., Miller, D. C., Fischbein, M. P., Woo, Y. J. 2020; 76 (14): 1703–13


    The Stanford classification of aortic dissection was described in 1970. The classification proposed that type A aortic dissection should be surgically repaired immediately, whereas type B aortic dissection can be treated medically. Since then, diagnostic tools and management of acute type A aortic dissection (ATAAD) have undergone substantial evolution. This paper evaluated historical changes of ATAAD repair at Stanford University since the establishment of the aortic dissection classification 50 years ago. The surgical approaches to the proximal and distal extent of the aorta, cerebral perfusion methods, and cannulation strategies were reviewed. Additional analyses using patients who underwent ATAAD repair at Stanford University from 1967 through December 2019 were performed to further illustrate the Stanford experience in the management of ATAAD. While technical complexity increased over time, post-operative survival continued to improve. Further investigation is warranted to delineate factors associated with the improved outcomes observed in this study.

    View details for DOI 10.1016/j.jacc.2020.07.061

    View details for PubMedID 33004136

  • Biomimetic six-axis robots replicate human cardiac papillary muscle motion: pioneering the next generation of biomechanical heart simulator technology. Journal of the Royal Society, Interface Imbrie-Moore, A. M., Park, M. H., Paulsen, M. J., Sellke, M. n., Kulkami, R. n., Wang, H. n., Zhu, Y. n., Farry, J. M., Bourdillon, A. T., Callinan, C. n., Lucian, H. J., Hironaka, C. E., Deschamps, D. n., Joseph Woo, Y. n. 2020; 17 (173): 20200614


    Papillary muscles serve as attachment points for chordae tendineae which anchor and position mitral valve leaflets for proper coaptation. As the ventricle contracts, the papillary muscles translate and rotate, impacting chordae and leaflet kinematics; this motion can be significantly affected in a diseased heart. In ex vivo heart simulation, an explanted valve is subjected to physiologic conditions and can be adapted to mimic a disease state, thus providing a valuable tool to quantitatively analyse biomechanics and optimize surgical valve repair. However, without the inclusion of papillary muscle motion, current simulators are limited in their ability to accurately replicate cardiac biomechanics. We developed and implemented image-guided papillary muscle (IPM) robots to mimic the precise motion of papillary muscles. The IPM robotic system was designed with six degrees of freedom to fully capture the native motion. Mathematical analysis was used to avoid singularity conditions, and a supercomputing cluster enabled the calculation of the system's reachable workspace. The IPM robots were implemented in our heart simulator with motion prescribed by high-resolution human computed tomography images, revealing that papillary muscle motion significantly impacts the chordae force profile. Our IPM robotic system represents a significant advancement for ex vivo simulation, enabling more reliable cardiac simulations and repair optimizations.

    View details for DOI 10.1098/rsif.2020.0614

    View details for PubMedID 33259750

  • Outcomes after heart retransplantation: A 50-year single-center experience. The Journal of thoracic and cardiovascular surgery Zhu, Y. n., Shudo, Y. n., Lingala, B. n., Baiocchi, M. n., Oyer, P. E., Woo, Y. J. 2020


    To evaluate outcomes after heart retransplantation.From January 6, 1968, to June 2019, 123 patients (112 adult and 11 pediatric patients) underwent heart retransplantation, and 2092 received primary transplantation at our institution. Propensity-score matching was used to account for baseline differences between the retransplantation and the primary transplantation-only groups. Kaplan-Meier survival analyses were performed. The primary end point was all-cause mortality, and secondary end points were postoperative complications.Retransplantation recipient age was 39.6 ± 16.4 years, and donor age was 26.4 ± 11.2 years. Ninety-two recipients (74.8%) were male. Compared with recipients who only underwent primary heart transplantation, retransplantation recipients were more likely to have hypertension (44/73.3% vs 774/53.3%, P = .0022), hyperlipidemia (40/66.7% vs 447/30.7%, P < .0001), and require dialysis (7/11.7% vs 42/2.9%, P = .0025). The indications for heart retransplantation were cardiac allograft vasculopathy (32/80%), primary graft dysfunction (6/15%), and refractory acute rejection (2/5%). After matching, postoperative outcomes such as hospital length of stay, severe primary graft dysfunction requiring intra-aortic balloon pump or extracorporeal membrane oxygenation, cerebral vascular accident, respiratory failure, renal failure requiring dialysis, and infection were similar between the 2 groups. Matched median survival after retransplantation was 4.6 years compared with 6.5 years after primary heart transplantation (log-rank P = .36, stratified log-rank P = .0063).In this single-center cohort, the unadjusted long-term survival after heart retransplantation was inferior to that after primary heart transplantation, and short-term survival difference persisted after propensity-score matching. Heart retransplantation should be considered for select patients for optimal donor organ usage.

    View details for DOI 10.1016/j.jtcvs.2020.06.121

    View details for PubMedID 32798029

  • A Novel Aortic Regurgitation Model from Cusp Prolapse with Hemodynamic Validation Using an Ex Vivo Left Heart Simulator. Journal of cardiovascular translational research Zhu, Y. n., Imbrie-Moore, A. M., Paulsen, M. J., Priromprintr, B. n., Park, M. H., Wang, H. n., Lucian, H. J., Farry, J. M., Woo, Y. J. 2020


    Although ex vivo simulation is a valuable tool for surgical optimization, a disease model that mimics human aortic regurgitation (AR) from cusp prolapse is needed to accurately examine valve biomechanics. To simulate AR, four porcine aortic valves were explanted, and the commissure between the two largest leaflets was detached and re-implanted 5 mm lower to induce cusp prolapse. Four additional valves were tested in their native state as controls. All valves were tested in a heart simulator while hemodynamics, high-speed videography, and echocardiography data were collected. Our AR model successfully reproduced cusp prolapse with significant increase in regurgitant volume compared with that of the controls (23.2 ± 8.9 versus 2.8 ± 1.6 ml, p = 0.017). Hemodynamics data confirmed the simulation of physiologic disease conditions. Echocardiography and color flow mapping demonstrated the presence of mild to moderate eccentric regurgitation in our AR model. This novel AR model has enormous potential in the evaluation of valve biomechanics and surgical repair techniques. Graphical Abstract.

    View details for DOI 10.1007/s12265-020-10038-z

    View details for PubMedID 32495264

  • Heart Transplant Using Hepatitis C-Seropositive and Viremic Organs in Seronegative Recipients. Annals of transplantation Zhu, Y. n., Shudo, Y. n., Lee, R. n., Woo, Y. J. 2020; 25: e922723


    BACKGROUND Hepatitis C virus (HCV)-seropositive donor hearts are underutilized for orthotopic heart transplantation (OHT). The advancement of direct-acting antiviral agent (DAA) treatment for HCV makes utilizing HCV-seropositive and viremic donor organs in HCV-seronegative recipients a possibility. MATERIAL AND METHODS From 1997 to 2019, adult patients who underwent OHT at our institution were retrospectively reviewed. Ten HCV-seronegative patients received HCV-seropositive donor hearts, 3 of which tested nucleic acid-positive. Kaplan-Meier curves were performed for survival analyses. This study was approved by the Institutional Review Board. RESULTS Recipient median age was 57.5 years old, and 2 (20%) were female. Donor median age was 42 years old, and 3 (30%) were female. One donor was cured from HCV with DAA prior to OHT. Four recipients developed hepatitis C viremia immediately after OHT. DAA treatment was completed in 3 recipients who demonstrated cure. Thirty-day and 1-year survival rates were both 80%. CONCLUSIONS We describe 10 HCV-seronegative patients who received HCV-seropositive donor hearts at our institution, with excellent short-term outcomes, even in those who received nucleic acid testing positive organs. DAA can be effective in treating hepatitis C viremia before and after OHT, with excellent recipient survival. Large clinical studies are needed to further evaluate the long-term outcomes of DAA therapy in patients after heart transplantation.

    View details for DOI 10.12659/AOT.922723

    View details for PubMedID 32527989

  • Quadrupling the N95 Supply during the COVID-19 Crisis with an Innovative 3D-Printed Mask Adaptor. Healthcare (Basel, Switzerland) Imbrie-Moore, A. M., Park, M. H., Zhu, Y. n., Paulsen, M. J., Wang, H. n., Woo, Y. J. 2020; 8 (3)


    The need for personal protective equipment during the COVID-19 pandemic is far outstripping our ability to manufacture and distribute these supplies to hospitals. In particular, the medical N95 mask shortage is resulting in healthcare providers reusing masks or utilizing masks with filtration properties that do not meet medical N95 standards. We developed a solution for immediate use: a mask adaptor, outfitted with a quarter section of an N95 respirator that maintains the N95 seal standard, thereby quadrupling the N95 supply. A variety of designs were 3D-printed and optimized based on the following criteria: seal efficacy, filter surface area and N95 respirator multiplicity. The final design is reusable and features a 3D-printed soft silicone base as well as a rigid 3D-printed cartridge to seal one-quarter of a 3M 1860 N95 mask. Our mask passed the computerized N95 fit test for six individuals. All files are publicly available with this publication. Our design can provide immediate support for healthcare professionals in dire need of medical N95 masks by extending the current supply by a factor of four.

    View details for DOI 10.3390/healthcare8030225

    View details for PubMedID 32717841

  • Artificial papillary muscle device for off-pump transapical mitral valve repair. The Journal of thoracic and cardiovascular surgery Imbrie-Moore, A. M., Zhu, Y. n., Park, M. H., Paulsen, M. J., Wang, H. n., Woo, Y. J. 2020


    New transapical minimally invasive artificial chordae implantation devices are a promising alternative to traditional open-heart repair, with the potential for decreased postoperative morbidity and reduced recovery time. However, these devices can place increased stress on the artificial chordae. We designed an artificial papillary muscle to alleviate artificial chordae stresses and thus increase repair durability.The artificial papillary muscle device is a narrow elastic column with an inner core that can be implanted during the minimally invasive transapical procedure via the same ventricular incision site. The device was 3-dimensionally printed in biocompatible silicone for this study. To test efficacy, porcine mitral valves (n = 6) were mounted in a heart simulator, and isolated regurgitation was induced. Each valve was repaired with a polytetrafluoroethylene suture with apical anchoring followed by artificial papillary muscle anchoring. In each case, a high-resolution Fiber Bragg Grating sensor recorded forces on the suture.Hemodynamic data confirmed that both repairs-with and without the artificial papillary muscle device-were successful in eliminating mitral regurgitation. Both the peak artificial chordae force and the rate of change of force at the onset of systole were significantly lower with the device compared with apical anchoring without the device (P < .001 and P < .001, respectively).Our novel artificial papillary muscle could integrate with minimally invasive repairs to shorten the artificial chordae and behave as an elastic damper, thus reducing sharp increases in force. With our device, we have the potential to improve the durability of off-pump transapical mitral valve repair procedures.

    View details for DOI 10.1016/j.jtcvs.2020.11.105

    View details for PubMedID 33451843

  • Engineered biomaterials for heart disease. Current opinion in biotechnology Stapleton, L. n., Zhu, Y. n., Woo, Y. J., Appel, E. n. 2020; 66: 246–54


    Ischemic heart disease is the most common type of heart disease, responsible for roughly 10 million deaths worldwide annually. While standard clinical interventions have resulted in improved patient outcomes, access to small diameter vessels required for cardiovascular interventions, and long-term patient mortality rates associated with eventual heart failure, remain critical challenges. In this current opinion piece we discuss novel methodologies for the advancement of vascular grafts, cardiac patches, and injectable drug delivery depot technologies as they relate to treatment of ischemic heart disease, including bilayered conduits, acellular bioactive extracellular matrix (ECM) scaffolds, and protease-responsive hydrogel delivery platforms. We address the motivation for innovation and current limitations in the field of engineered biomaterials for myocardial ischemia therapeutics and interventions.

    View details for DOI 10.1016/j.copbio.2020.08.008

    View details for PubMedID 33011453

  • Comprehensive Ex Vivo Comparison of 5 Clinically Used Conduit Configurations for Valve-Sparing Aortic Root Replacement Using a 3-Dimensional-Printed Heart Simulator. Circulation Paulsen, M. J., Imbrie-Moore, A. M., Baiocchi, M. n., Wang, H. n., Hironaka, C. E., Lucian, H. J., Farry, J. M., Thakore, A. D., Zhu, Y. n., Ma, M. n., MacArthur, J. W., Woo, Y. J. 2020; 142 (14): 1361–73


    Many graft configurations are clinically used for valve-sparing aortic root replacement, some specifically focused on recapitulating neosinus geometry. However, the specific impact of such neosinuses on valvular and root biomechanics and the potential influence on long-term durability are unknown.Using a custom 3-dimenstional-printed heart simulator with porcine aortic roots (n=5), the anticommissural plication, Stanford modification, straight graft (SG), Uni-Graft, and Valsalva graft configurations were tested in series using an incomplete counterbalanced measures design, with the native root as a control, to mitigate ordering effects. Hemodynamic and videometric data were analyzed using linear models with conduit as the fixed effect of interest and valve as a fixed nuisance effect with post hoc pairwise testing using Tukey's correction.Hemodynamics were clinically similar between grafts and control aortic roots. Regurgitant fraction varied between grafts, with SG and Uni-Graft groups having the lowest regurgitant fractions and anticommissural plication having the highest. Root distensibility was significantly lower in SG versus both control roots and all other grafts aside from the Stanford modification (P≤0.01 for each). All grafts except SG had significantly higher cusp opening velocities versus native roots (P<0.01 for each). Relative cusp opening forces were similar between SG, Uni-Graft, and control groups, whereas anticommissural plication, Stanford modification, and Valsalva grafts had significantly higher opening forces versus controls (P<0.01). Cusp closing velocities were similar between native roots and the SG group, and were significantly lower than observed in the other conduits (P≤0.01 for each). Only SG and Uni-Graft groups experienced relative cusp closing forces approaching that of the native root, whereas relative forces were >5-fold higher in the anticommissural plication, Stanford modification, and Valsalva graft groups.In this ex vivo modeling system, clinically used valve-sparing aortic root replacement conduit configurations have comparable hemodynamics but differ in biomechanical performance, with the straight graft most closely recapitulating native aortic root biomechanics.

    View details for DOI 10.1161/CIRCULATIONAHA.120.046612

    View details for PubMedID 33017215

  • Redo Valve-Sparing Root Replacement for Delayed Cusp Derangement From Ventricular Septal Defect ANNALS OF THORACIC SURGERY Zhu, Y., Cohen, J. E., Ma, M., Woo, Y. 2019; 108 (5): E295–E296
  • Multidisciplinary approach utilizing early, intensive physical rehabilitation to accelerate recovery from veno-venous extracorporeal membrane oxygenation EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Zhu, Y., Bankar, D., Shudo, Y., Woo, Y. 2019; 56 (4): 811–12
  • Integrated Thoracic Surgery Residency: Current Status and Future Evolution SEMINARS IN THORACIC AND CARDIOVASCULAR SURGERY Zhu, Y., Goldstone, A. B., Woo, Y. 2019; 31 (3): 345–49
  • Redo Valve-Sparing Root Replacement for Delayed Cusp Derangement from Ventricular Septal Defect. The Annals of thoracic surgery Zhu, Y., Cohen, J. E., Ma, M., Woo, Y. J. 2019


    A 28-year-old gentleman with ventricular septal defect (VSD), double-chambered right ventricle (DCRV) with associated right ventricular outflow tract obstruction, and anomalous right coronary artery (RCA) underwent resection of the DCRV, trans-aortic VSD repair, and unroofing of anomalous RCA. Two years later, he returned with delayed presentation of VSD flow funnel related aortic cusp prolapse and symptomatic severe aortic regurgitation. He underwent reoperative valve-sparing aortic root replacement and aortic cusp repair with an excellent outcome.

    View details for PubMedID 30986415

  • Multidisciplinary approach utilizing early, intensive physical rehabilitation to accelerate recovery from veno-venous extracorporeal membrane oxygenation. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Zhu, Y., Bankar, D., Shudo, Y., Woo, Y. J. 2019


    This case demonstrates the benefits of our early, intensive physical rehabilitation intervention to prevent the natural sequelae occurring from prolonged bed rest. This minimizes neuromuscular weakness and optimizes strength, endurance and cardiorespiratory function, thus accelerating recovery from a long duration of femorally cannulated veno-venous extracorporeal membrane oxygenation.

    View details for PubMedID 30796438

  • Impact of "increased-risk" donor hearts on transplant outcomes: A propensity-matched analysis. The Journal of thoracic and cardiovascular surgery Shudo, Y., Cohen, J. E., Lingala, B., He, H., Zhu, Y., Woo, Y. J. 2019; 157 (2): 603–10


    OBJECTIVES: Orthotopic heart transplantation (OHT) remains the gold standard for advanced heart failure. Increased risk (IR) donors were categorized by the United Network for Organ Sharing Database (UNOS) according to the Centers for Disease Control and Prevention (CDC) criteria. However, the impact of CDC IR donor hearts on the outcome of adult OHT recipients remains unclear. The aim of this study was to compare the outcome of adult OHT recipients between CDC IR and non-CDC IR donor grafts.METHODS: Data were obtained from the United Network for Organ Sharing Databas. All adult patients (age ≥18years) undergoing OHT from 2004 through 2016 were included (n=24,751). Propensity scores for CDC IR donors were calculated by estimating probabilities of CDC IR donor graft use using a nonparsimonious multivariable logistic regression model. Patients were matched 1:1 using a greedy matching algorithm based on the propensity score of each patient. The impact of CDC IR donors on the post-transplant outcomes, such as 30-day and overall mortalities, was investigated using Cox-proportional hazards. Overall survival probability analyses were performed.RESULTS: Of 24,751 primary heart transplants from 2004 to 2016 with 3584 (14.5%) as IR donors, 6304 transplants were successfully matched (n=3152 in CDC IR group and non-IR group). There were no significant differences in baseline characteristics in recipients and donors. In the Cox-proportional hazards model for matched subjects, the use of CDC IR grafts was not associated with 30-day (hazard ratio of IR group vs non-IR group 0.97; 95% confidence interval, 0.87-1.08; P=.57) and overall mortalities (hazard ratio, 0.94; 95% confidence interval, 0.73-1.21; P=.62). Interestingly, post-transplant acute myocardial rejection episodes during hospital stays were found more often in the CDC-IR group, compared with the non-CDC IR group (CDC IR, n=358 [11.4%]; non-CDC IR, n=304 [9.6%] P = .03), whereas post-transplant pacemaker placements were performed less frequently in the CDC IR group (CDC IR, n=80 [2.6%]; non-CDC IR, n=111 [3.5%] P = .020). Importantly, there was no significant difference in the overall survival probability between CDC IR and non-IR groups in both unadjusted and adjusted survival analyses.CONCLUSIONS: CDC IR status does not have a significant impact on adult OHT recipient survival probability. Increased use of CDC IR donor grafts can potentially alleviate the persistent and worsening shortage of available donor organs and shorten the waitlist time for heart transplantation.

    View details for PubMedID 30669225

  • Loeys-Dietz syndrome: Intermediate-term outcomes of medically and surgically managed patients. The Journal of thoracic and cardiovascular surgery Aftab, M., Cikach, F. S., Zhu, Y., Idrees, J. J., Rigelsky, C. M., Kalahasti, V., Roselli, E. E., Svensson, L. G. 2019; 157 (2): 439-450.e5


    Loeys-Dietz syndrome (LDS) is an aggressive connective tissue disorder associated with increased risk of aortic dissection and aneurysm rupture at an early age and smaller aortic diameters. We report our experience with LDS to better understand its natural history and treatment outcomes and help establish treatment guidelines.We retrospectively reviewed all patients with LDS who underwent medical or surgical treatment at Cleveland Clinic before April 27, 2017. Primary endpoints were postoperative in-hospital morbidity and mortality. Secondary endpoints were aorta-related reoperations and short- and long-term mortality.We identified 53 patients with LDS. Of these, 33 (62%) underwent aortic surgery. Mean age was 39 ± 14 years, and mean maximum aortic diameter was 4.3 cm. There were 2 (6%) deaths after urgent or emergency surgery. Twenty-two patients (67%) required no aortic reoperation; 20 of these had prophylactic surgery. Multiple aortic operations were performed on 11 (33%) patients, 9 of whom experienced aortic dissections. Six patients (18%) required total aortic replacement. Among 19 patients with modified root reimplantation, no aorta- or valve-related complications occurred. Overall, 33 patients underwent 58 aortic and 81 cardiovascular operations, with 1 late death. Kaplan-Meier survival of the aortic-surgery cohort was 89% at 10 years (median follow-up 5.2 years). There were no late deaths in the non-aortic surgery group (20/53; 38%).Prophylactic aortic surgical outcomes in LDS are excellent. Surgical reintervention remains high, particularly after aortic dissections. Close surveillance of medically managed and postoperative patients and early prophylactic surgery are crucial to avoid aortic catastrophe and achieve a good long-term prognosis.

    View details for DOI 10.1016/j.jtcvs.2018.03.172

    View details for PubMedID 30669217

  • Surgical Management for Aortoesophageal Fistula After Endovascular Aortic Repair. The Annals of thoracic surgery Zhu, Y. n., MacArthur, J. W., Lui, N. n., Lee, A. M. 2019


    This case demonstrates successful surgical management of a 6 cm-long aortoesophageal fistula from an infected stent graft. A 69-year-old woman with a penetrating descending thoracic aortic ulcer underwent endovascular aortic repair. Two weeks later, she presented with nausea and melena, and was found to have an infected stent graft on imaging. She underwent a two-stage procedure encompassing aortic arch debranching and extra-anatomic aortic bypass in stage one, and stent graft resection, primary esophageal repair, intercostal and omental flap and jejunostomy tube placement in stage two. She was discharged one month later and is doing well 1.5 years after the operation.

    View details for DOI 10.1016/j.athoracsur.2019.08.076

    View details for PubMedID 31586613

  • 50 Year Heart Transplantation Ultra Long-Term Outcomes - The Stanford Experience Zhu Yuanjia, Shudo, Y., Lingala, B., Yasukawa, L., Loh, E., Oyer, P. E., Woo, Y. J. LIPPINCOTT WILLIAMS & WILKINS. 2018
  • Successful heart-lung-kidney and domino heart transplantation following veno-venous extracorporeal membrane oxygenation support. Interactive cardiovascular and thoracic surgery Zhu, Y., Shudo, Y., Lee, A. M., Woo, Y. J. 2018


    A 60-year-old man with cystic fibrosis, mediastinal shift and end-stage kidney disease underwent a heart-lung-kidney transplantation. His explanted heart was used for a domino heart transplantation. This case showed an excellent outcome, even with high preoperative acuity requiring veno-venous extracorporeal membrane oxygenation and continuous veno-venous haemodialysis.

    View details for PubMedID 30113636

  • Cardiac Surgery Outcomes in Patients With Chronic Lymphocytic Leukemia. The Annals of thoracic surgery Zhu, Y., Toth, A. J., Lowry, A. M., Blackstone, E. H., Hill, B. T., Mick, S. L. 2018; 105 (4): 1182-1191


    Surgical outcomes of patients with chronic lymphocytic leukemia (CLL) undergoing cardiac surgery are limited. Our objectives were to investigate hospital morbidity and mortality after open cardiac surgery in CLL versus non-CLL patients.From May 1995 to May 2015, 157 patients with CLL and 55,917 without and older than 47 years underwent elective cardiac surgery at Cleveland Clinic. By Rai criteria, 79 CLL patients (56%) were low risk (class 0), 13 (9.1%) intermediate risk (classes I and II), and 38 (27%) high risk (classes III and IV); 12 (8.5%) were in remission. Mean age of CLL patients was 72 ± 9.0 years, and 18% were women. CLL patients were propensity-score matched to 3 non-CLL patients to compare surgical outcomes.High-risk CLL patients received more blood products than matched non-CLL patients (33/38 [87%] versus 74/114 [65%], p = 0.01), but were less likely to receive cryoprecipitate (0% versus 15/114 [13%], p = .02). Intermediate-risk CLL patients received more platelet units, mean 12 versus 4.6 (p = 0.008). Occurrence of deep sternal wound infection (0% versus 5/471 [1.1%]), septicemia (5/157 [3.2%] versus 14/471 [3.0%]), and hospital mortality (4/157 [2.5%] versus 14/471 [3.0%]) were similar (p > 0.3), independent of prior chemotherapy treatment for CLL.Although CLL patients did not have higher hospital mortality than non-CLL patients, high-risk CLL patients were more likely to receive blood products. Risks associated with transfusion should be considered when evaluating CLL patients for elective cardiac surgery. Appropriate preoperative management, such as blood product transfusions, and alternative treatment options that decrease blood loss, should be considered for high-risk patients.

    View details for DOI 10.1016/j.athoracsur.2017.11.014

    View details for PubMedID 29455840

  • Machine-learning phenotypic classification of bicuspid aortopathy. The Journal of thoracic and cardiovascular surgery Wojnarski, C. M., Roselli, E. E., Idrees, J. J., Zhu, Y., Carnes, T. A., Lowry, A. M., Collier, P. H., Griffin, B., Ehrlinger, J., Blackstone, E. H., Svensson, L. G., Lytle, B. W. 2018; 155 (2): 461-469.e4


    Bicuspid aortic valves (BAV) are associated with incompletely characterized aortopathy. Our objectives were to identify distinct patterns of aortopathy using machine-learning methods and characterize their association with valve morphology and patient characteristics.We analyzed preoperative 3-dimensional computed tomography reconstructions for 656 patients with BAV undergoing ascending aorta surgery between January 2002 and January 2014. Unsupervised partitioning around medoids was used to cluster aortic dimensions. Group differences were identified using polytomous random forest analysis.Three distinct aneurysm phenotypes were identified: root (n = 83; 13%), with predominant dilatation at sinuses of Valsalva; ascending (n = 364; 55%), with supracoronary enlargement rarely extending past the brachiocephalic artery; and arch (n = 209; 32%), with aortic arch dilatation. The arch phenotype had the greatest association with right-noncoronary cusp fusion: 29%, versus 13% for ascending and 15% for root phenotypes (P < .0001). Severe valve regurgitation was most prevalent in root phenotype (57%), followed by ascending (34%) and arch phenotypes (25%; P < .0001). Aortic stenosis was most prevalent in arch phenotype (62%), followed by ascending (50%) and root phenotypes (28%; P < .0001). Patient age increased as the extent of aneurysm became more distal (root, 49 years; ascending, 53 years; arch, 57 years; P < .0001), and root phenotype was associated with greater male predominance compared with ascending and arch phenotypes (94%, 76%, and 70%, respectively; P < .0001). Phenotypes were visually recognizable with 94% accuracy.Three distinct phenotypes of bicuspid valve-associated aortopathy were identified using machine-learning methodology. Patient characteristics and valvular dysfunction vary by phenotype, suggesting that the location of aortic pathology may be related to the underlying pathophysiology of this disease.

    View details for DOI 10.1016/j.jtcvs.2017.08.123

    View details for PubMedID 29042101

  • Combined Transapical Transcatheter Aortic Valve Replacement and Thoracic Endovascular Aortic Repair for Severe Aortic Stenosis and Arch Aneurysm. Aorta (Stamford, Conn.) Zhu, Y., Roselli, E. E., Idrees, J. J., Kapadia, S., Svensson, L. G. 2016; 4 (5): 175-177


    An 83-year-old male with multiple comorbidities presented with critical aortic stenosis and a saccular aortic arch aneurysm. Through a mini thoracotomy, a balloon expandable transcatheter aortic valve was delivered transapically. A thoracic stent graft was then delivered through the prosthetic valve and deployed in the arch, while a covered stent was deployed in the left common carotid artery. Three-year postoperative computed tomography showed a thrombosed arch aneurysm with decreased size. This case demonstrates the feasibility of using combined transapical transcatheter technologies to treat multicomponent disease in a high-risk patient during a single operation.

    View details for DOI 10.12945/j.aorta.2016.16.030

    View details for PubMedID 28516094

    View details for PubMedCentralID PMC5425272

  • Reoperative transapical transcatheter aortic valve replacement for central aortic regurgitation. Journal of cardiac surgery Zhu, Y., Kapadia, S., Krishnaswamy, A., Svensson, L. G., Mick, S. 2016; 31 (9): 572-4


    Paravalvular leak-related aortic regurgitation after transcatheter aortic valve replacement (TAVR) is a common complication and is associated with increased short- and long-term mortality. However, the impact of isolated central aortic regurgitation is unknown. We report a case of transapical (TA) TAVR with postprocedural central aortic regurgitation, who returned after two years with progression of regurgitation. A reoperative valve-in-valve TA-TAVR was performed.

    View details for DOI 10.1111/jocs.12798

    View details for PubMedID 27405799

  • Atypical Findings in Massive Bupropion Overdose: A Case Report and Discussion of Psychopharmacologic Issues. Journal of psychiatric practice Zhu, Y., Kolawole, T., Jimenez, X. F. 2016; 22 (5): 405-9


    Bupropion is an atypical antidepressant that is structurally similar to amphetamines. Its primary toxic effects include seizure, sinus tachycardia, hypertension, and agitation; however, at higher amounts of ingestion, paradoxical cardiac effects are seen. We report the case of a 21-year-old woman who ingested 13.5 g of bupropion, a dose higher than any other previously reported. The patient presented with seizure, sinus tachycardia with prolonged QTc and QRS intervals, dilated pupils, and agitation. Four days after overdose, the patient's sinus tachycardia and prolonged QTc and QRS intervals resolved with symptomatic management, but she soon developed sinus bradycardia, hypotension, and mild transaminitis. With continued conservative management and close monitoring, her sinus bradycardia resolved 8 days after the overdose. The transaminitis resolved 12 days after the overdose. Our findings are consistent with previously reported toxic effects associated with common overdose amounts of bupropion. In addition, we have observed transient cardiotoxicity manifesting as sinus bradycardia associated with massive bupropion overdose. These findings are less frequently reported and must be considered when managing patients with massive bupropion overdose. We review the psychopharmacologic implications of this and comment on previous literature.

    View details for DOI 10.1097/PRA.0000000000000179

    View details for PubMedID 27648505

  • Outcomes After Operations for Unicuspid Aortic Valve With or Without Ascending Repair in Adults. The Annals of thoracic surgery Zhu, Y., Roselli, E. E., Idrees, J. J., Wojnarski, C. M., Griffin, B., Kalahasti, V., Pettersson, G., Svensson, L. G. 2016; 101 (2): 613-9


    Unicuspid aortic valve is an important subset of bicuspid aortic valve, and knowledge regarding its aortopathy pattern and surgical outcomes is limited. Our objectives were to characterize unicuspid aortic valve patients, associated aortopathy, and surgical outcomes.From January 1990 to May 2013, 149 adult unicuspid aortic valve patients underwent aortic valve replacement or repair for aortic stenosis (n = 13), regurgitation (n = 13), or both (n = 123), and in 91 (61%) the aortic valve operation was combined with aortic repair. Data were obtained from the Cardiovascular Information Registry and medical record review. Three-dimensional imaging analysis was performed from preoperative computed tomography and magnetic resonance imaging scans. The Kaplan-Meier method was used for survival analysis.Patients had a mean maximum aortic diameter of 44 ± 8 mm and variably involved the aortic root, ascending, or arch, or both. Patients with valve operations alone were more likely to be hypertensive (p = 0.01) and to have severe aortic stenosis (p = 0.07) than those who underwent concurrent aortic operations. There were no operative deaths, strokes, or myocardial infarctions. Patients undergoing aortic repair had better long-term survival. Estimated survival at 1, 5, and 10 years was 100%, 100%, and 100% after combined operations and was 100%, 88%, and 88% after valve operations alone (p = 0.01).Patients with a dysfunctional unicuspid aortic valve frequently present with an ascending aneurysm that requires repair. Combined aortic valve operations and aortic repair was associated with significantly better long-term survival than a valve operation alone. Further study of this association may direct decisions about timing of surgical intervention.

    View details for DOI 10.1016/j.athoracsur.2015.07.058

    View details for PubMedID 26453423

    View details for PubMedCentralID PMC5152623

  • Nanocytology of rectal colonocytes to assess risk of colon cancer based on field cancerization. Cancer research Damania, D., Roy, H. K., Subramanian, H., Weinberg, D. S., Rex, D. K., Goldberg, M. J., Muldoon, J., Cherkezyan, L., Zhu, Y., Bianchi, L. K., Shah, D., Pradhan, P., Borkar, M., Lynch, H., Backman, V. 2012; 72 (11): 2720-7


    Developing a minimally invasive and cost-effective prescreening strategy for colon cancer is critical because of the impossibility of conducting colonoscopy on the entire at-risk population. The concept of field carcinogenesis, in which normal-appearing tissue away from a tumor has molecular and, consequently, nano-architectural abnormalities, offers one attractive approach to identify high-risk patients. In this study, we investigated whether the novel imaging technique partial wave spectroscopic (PWS) microscopy could risk-stratify patients harboring precancerous lesions of the colon, using an optically measured biomarker (L(d)) obtained from microscopically normal but nanoscopically altered cells. Rectal epithelial cells were examined from 146 patients, including 72 control patients, 14 patients with diminutive adenomas, 20 patients with nondiminutive/nonadvanced adenomas, 15 patients with advanced adenomas/high-grade dysplasia, 12 patients with genetic mutation leading to Lynch syndrome, and 13 patients with cancer. We found that the L(d) obtained from rectal colonocytes was well correlated with colon tumorigenicity in our patient cohort and in an independent validation set of 39 additional patients. Therefore, our findings suggest that PWS-measured L(d) is an accurate marker of field carcinogenesis. This approach provides a potential prescreening strategy for risk stratification before colonoscopy.

    View details for DOI 10.1158/0008-5472.CAN-11-3807

    View details for PubMedID 22491589

    View details for PubMedCentralID PMC3557939