Professional Education

  • 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

  • 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. 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

  • 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

  • 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

  • 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

  • Loeys-Dietz syndrome: Intermediate-term outcomes of medically and surgically managed patients. The Journal of thoracic and cardiovascular surgery Aftab, M. n., Cikach, F. S., Zhu, Y. n., Idrees, J. J., Rigelsky, C. M., Kalahasti, V. n., Roselli, E. E., Svensson, L. G. 2019; 157 (2): 439–50.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

  • 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

  • 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. n., Carnes, T. A., Lowry, A. M., Collier, P. H., Griffin, B. n., Ehrlinger, J. n., Blackstone, E. H., Svensson, L. G., Lytle, B. W. 2018; 155 (2): 461–69.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

  • Cardiac Surgery Outcomes in Patients With Chronic Lymphocytic Leukemia. The Annals of thoracic surgery Zhu, Y. n., Toth, A. J., Lowry, A. M., Blackstone, E. H., Hill, B. T., Mick, S. L. 2018; 105 (4): 1182–91


    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

  • Outcomes After Operations for Unicuspid Aortic Valve With or Without Ascending Repair in Adults. The Annals of thoracic surgery Zhu, Y. n., Roselli, E. E., Idrees, J. J., Wojnarski, C. M., Griffin, B. n., Kalahasti, V. n., Pettersson, G. n., Svensson, L. G. 2016; 101 (2): 613–19


    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

  • Combined Transapical Transcatheter Aortic Valve Replacement and Thoracic Endovascular Aortic Repair for Severe Aortic Stenosis and Arch Aneurysm. Aorta (Stamford, Conn.) Zhu, Y. n., Roselli, E. E., Idrees, J. J., Kapadia, S. n., Svensson, L. G. 2016; 4 (5): 175–77


    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

  • Atypical Findings in Massive Bupropion Overdose: A Case Report and Discussion of Psychopharmacologic Issues. Journal of psychiatric practice Zhu, Y. n., Kolawole, T. n., 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

  • Reoperative transapical transcatheter aortic valve replacement for central aortic regurgitation. Journal of cardiac surgery Zhu, Y. n., Kapadia, S. n., Krishnaswamy, A. n., Svensson, L. G., Mick, S. n. 2016; 31 (9): 572–74


    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

  • Nanocytology of rectal colonocytes to assess risk of colon cancer based on field cancerization. Cancer research Damania, D. n., Roy, H. K., Subramanian, H. n., Weinberg, D. S., Rex, D. K., Goldberg, M. J., Muldoon, J. n., Cherkezyan, L. n., Zhu, Y. n., Bianchi, L. K., Shah, D. n., Pradhan, P. n., Borkar, M. n., Lynch, H. n., Backman, V. n. 2012; 72 (11): 2720–27


    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