Academic Appointments

Professional Education

  • MD, Columbia University, College of Physicians and Surgeons, Medicine (2015)
  • BA, Harvard University, Molecular and Cellular Biology, Music (2011)

Current Research and Scholarly Interests

Precision surgery: patient-specific bypass grafting and valve repair strategies
Autonomous robotic surgery
Photosynthetic therapies to circumvent myocardial ischemia
Collateral artery formation as protection against myocardial infarction
Angiogenesis and myocardial regeneration to prevent heart failure
Tissue engineering to limit ventricular remodeling
Understanding the biomechanics of injured and failing hearts

Current Clinical Interests

  • Coronary Revascularization
  • Heart Transplantation
  • Mitral Valve Repair
  • Minimally Invasive Surgery
  • Robotics
  • Thoracic Aortic Aneurysm
  • Aortic Valve Repair
  • Ventricular Assist Devices

All Publications

  • Biodegradable external wrapping promotes favorable adaptation in an ovine vein graft model. Acta biomaterialia Ramachandra, A. B., Wang, H., Wnorowski, A., Schwarz, E. L., Pickering, J., Heiler, J. C., Lucian, H. J., Hironaka, C. E., Tran, N. A., Liu, Y., Khan, M. O., Obafemi, O., Tada, Y., Kahn, A. M., Sayed, N., Wu, J. C., Humphrey, J. D., Boyd, J., Marsden, A. L. 2022


    Vein grafts, the most commonly used conduits in multi-vessel coronary artery bypass grafting surgery, have high intermediate- and long-term failure rates. The abrupt and marked increase in hemodynamic loads on the vein graft is a known contributor to failure. Recent computational modeling suggests that veins can more successfully adapt to an increase in mechanical load if the rate of loading is gradual. Applying an external wrap or support at the time of surgery is one way to reduce the transmural load, and this approach has improved performance relative to an unsupported vein graft in several animal studies. Yet, a clinical trial in humans has shown benefits and drawbacks, and mechanisms by which an external wrap affects vein graft adaptation remain unknown. This study aims to elucidate such mechanisms using a multimodal experimental and computational data collection pipeline. We quantify morphometry using magnetic resonance imaging, mechanics using biaxial testing, hemodynamics using computational fluid dynamics, structure using histology, and transcriptional changes using bulk RNA-sequencing in an ovine carotid-jugular interposition vein graft model, without and with an external biodegradable wrap that allows loads to increase gradually. We show that a biodegradable external wrap promotes luminal uniformity, physiological wall shear stress, and a consistent vein graft phenotype, namely, it prevents over-distension, over-thickening, intimal hyperplasia, and inflammation, and it preserves mechanotransduction. These mechanobiological insights into vein graft adaptation in the presence of an external support can inform computational growth and remodeling models of external support and facilitate design and manufacturing of next-generation external wrapping devices. STATEMENT OF SIGNIFICANCE: External mechanical support is emerging as a promising technology to prevent vein graft failure following coronary bypass graft surgery. While variants of this technology are currently under investigation in clinical trials, the fundamental mechanisms of adaptation remain poorly understood. We employ an ovine carotid-jugular interposition vein graft model, with and without an external biodegradable wrap to provide mechanical support, and probe vein graft adaptation using a multimodal experimental and computational data collection pipeline. We quantify morphometry using magnetic resonance imaging, mechanics using biaxial testing, fluid flow using computational fluid dynamics, vascular composition and structure using histology, and transcriptional changes using bulk RNA sequencing. We show that the wrap mitigates vein graft failure by promoting multiple adaptive mechanisms (across biological scales).

    View details for DOI 10.1016/j.actbio.2022.08.029

    View details for PubMedID 35995404

  • Diminishing Basic Science Research Experience Among United States Cardiothoracic Surgery Trainees. The Journal of surgical research Wang, H., Bajaj, S. S., Manjunatha, K., Yu, M. M., Obafemi, O. O., Williams, K. M., Boyd, J. H. 2022; 279: 312-322


    INTRODUCTION: There is growing concern regarding the attrition of surgeon-scientists. To understand the decline of basic science research (BSR), it is essential to examine trends in research conducted by trainees. We hypothesized that, over recent decades, cardiothoracic (CT) surgery trainees have published fewer BSR articles.MATERIALS AND METHODS: CT surgeons at United States training institutions in 2020 who completed training in the past threedecades, excluding international trainees, were analyzed (1991-2000: n=148; 2001-2010: n=228; 2011-2020: n=247). Publication records were obtained from Scopus. Articles with medical subject heading terms involving molecular/cellular or animal research were classified as BSR using the National Institutes of Health iCite Translation module. Data were analyzed using Fisher's exact test or the Wilcoxon rank-sum test.RESULTS: While the proportion of surgeons who published a first-author paper during training remained stable over the past twodecades (178/228 [78.1%] versus 189/247 [76.5%], P=0.7427), the proportion who published a first-author BSR paper decreased significantly (135/228 [59.2%] versus 96/247 [38.9%], P<0.0001). Among surgeons who published a first-author paper in training, the total papers published by each trainee did not change over the past twodecades (3.5 versus 3.3 first-author papers per 10y of training, P=0.8819). However, the number of BSR papers published during training decreased significantly (1.7 versus 0.8 first-author papers per 10y of training, P<0.0001).CONCLUSIONS: CT surgery trainees are publishing fewer BSR papers. Additional efforts are needed to increase exposure of trainees to BSR and reaffirm that BSR is a valuable and worthwhile pursuit for academic surgeons.

    View details for DOI 10.1016/j.jss.2022.06.020

    View details for PubMedID 35809356

  • Quantitative goals for research output and scholarly impact to enhance basic science R01 grant renewal for cardiothoracic surgeons. JTCVS open Wang, H., Bajaj, S. S., Heiler, J. C., Krishnan, A., Williams, K. M., Woo, Y. J., Boyd, J. H. 2022; 9: 162-175


    Objectives: Cardiothoracic (CT) surgeons with National Institutes of Health (NIH) R01 funding face a highly competitive renewal process. The factors that contribute to successful grant renewal for CT surgeons remain poorly defined. We hypothesized that renewed basic science grants are associated with high research output and scholarly impact during the preceding award cycle.Methods: Using a database of academic CT surgeons (n=992) at accredited training institutions in 2018, we identified basic science R01 grants awarded to CT surgeon principal investigators since 1985. Data for each award were obtained from publicly available online sources. Scholarly impact was evaluated using the NIH-validated relative citation ratio (RCR), defined as an article's citation rate divided by that of R01-funded publications in the same field. Continuous data are presented as medians and analyzed using the Mann-Whitney test.Results: We identified 102 basic science R01 award cycles, including 33 that were renewed (32.4%). Renewed and nonrenewed awards had a similar start year and funding period. Principal investigators of renewed versus nonrenewed awards were similar in surgical subspecialty, research training, attending experience, academic rank, and previous NIH funding. Renewed awards produced more publications per year over the funding cycle (3.4 vs 1.5; P=.0010) and exhibited a greater median RCR during the funding cycle (0.84 vs 0.66; P=.0183).Conclusions: CT surgery basic science R01 grants are associated with high research output and scholarly impact. At the 50th percentile among renewed grants, CT surgeons published 3.4 funded manuscripts per year with a median RCR of 0.84 during the previous award cycle.

    View details for DOI 10.1016/j.xjon.2021.10.063

    View details for PubMedID 36003453

  • 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

  • The impact of the American Association for Thoracic Surgery on National Institutes of Health grant funding for cardiothoracic surgeons. The Journal of thoracic and cardiovascular surgery Mehaffey, J. H., Wang, H., Narahari, A. K., Bajaj, S. S., Chandrabhatla, A. S., Krupnick, A. S., Sellke, F. W., Rosengart, T. K., Woo, Y. J. 2021


    OBJECTIVES: The American Association for Thoracic Surgery, through its annual meeting, pilot grant funding, Scientific Affairs and Government Relations Committee activity, and academic development programs (Grant Writing Workshop, Clinical Trials Course, Innovation Summit), has aimed to develop the research careers of cardiothoracic surgeons. We hypothesized that American Association for Thoracic Surgery activities have helped increase National Institutes of Health grants awarded to cardiothoracic surgeons.METHODS: A database of 1869 academic cardiothoracic surgeons in the United States was created in December 2020. National Institutes of Health grant records from 1985 to 2020 were obtained for each surgeon using National Institutes of Health Research Portfolio Online Reporting Tools Expenditures and Results. Analyses were normalized to the number of active surgeons per year, based on the year of each surgeon's earliest research publication on Scopus.RESULTS: A total of 346 cardiothoracic surgeons have received 696 National Institutes of Health grants totaling more than $1.5 billion in funding, with 48 surgeons actively serving as principal investigator of 66 R01 grants in 2020. The prevalence of research grants (7.4 vs 5.6 grants per 100 active surgeons, P<.0001), percentage of surgeons with a research grant (5.3% vs 4.7%, P=.0342), and number of research grants per funded surgeon (1.4 vs 1.2 grants, P<.0001) were significantly greater during the Scientific Affairs and Government Relations era (2003-2020) than the pre-Scientific Affairs and Government Relations era (1985-2002). The incidence of new research grants after surgeon participation in an American Association for Thoracic Surgery academic development program was significantly greater than that in the absence of participation (3.5 vs 1.1 new grants per 100 surgeons per year, P<.0001).CONCLUSIONS: Through dedicated efforts and programs, the American Association for Thoracic Surgery has provided effective support to help increase National Institutes of Health grant funding awarded to cardiothoracic surgeons.

    View details for DOI 10.1016/j.jtcvs.2021.10.031

    View details for PubMedID 34809972

  • 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

  • Characterization of Cardiothoracic Surgeons Actively Leading Basic Science Research. The Journal of surgical research Wang, H., Bajaj, S. S., Krishnan, A., Heiler, J. C., Williams, K. M., Pickering, J. M., Manjunatha, K., Sanchez, M., O'Donnell, C. T., Boyd, J. H. 2021; 268: 371-380


    There is increasing concern regarding the attrition of surgeon-scientists in cardiothoracic (CT) surgery. However, the characteristics of CT surgeons who are actively leading basic science research (BSR) have not been examined. We hypothesized that early exposure to BSR during training and active grant funding are important factors that facilitate the pursuit of BSR among practicing CT surgeons.We created a database of 992 CT surgeons listed as faculty at accredited United States CT surgery teaching hospitals in 2018. Data regarding each surgeon's training/professional history, publication record, and National Institutes of Health funding were acquired from publicly available online sources. Surgeons who published at least one first- or last-author paper in 2017-2018 were considered to be active, lead researchers.Of the 992 CT surgeons, 73 (7.4%) were actively leading BSR, and 599 (60.4%) were actively leading only non-BSR. Only 2 women were actively leading BSR. Surgeons actively leading BSR were more likely to have earned a PhD degree (20.5% versus 9.7%, P = 0.0049), and more likely to have published a first-author BSR paper during training (76.7% versus 40.9%, P< 0.0001). Surgeons actively leading BSR were also more likely to have an active National Institutes of Health grant (34.2% versus 5.8%, P< 0.0001), especially an R01 grant (21.9% versus 2.5%, P< 0.0001).A small minority of CT surgeons at academic training hospitals are actively leading BSR. In order to facilitate the development of surgeon-scientists, additional support must be given to trainees and junior faculty, especially women, to enable early engagement in BSR.

    View details for DOI 10.1016/j.jss.2021.06.065

    View details for PubMedID 34399359

  • Early Engagement in Cardiothoracic Surgery Research Enhances Future Academic Productivity. The Annals of thoracic surgery Wang, H., Bajaj, S. S., Williams, K. M., Heiler, J. C., Pickering, J. M., Manjunatha, K., O'Donnell, C. T., Sanchez, M., Boyd, J. H. 2020


    BACKGROUND: Early engagement in cardiothoracic (CT) surgery research may help attract trainees to academic CT surgery, but whether this early exposure boosts career-long academic achievement remains unknown.METHODS: A database of all CT surgery faculty at accredited, academic CT surgery training programs in the United States during the year 2018 was established. Excluding international medical graduates, surgeons who started general surgery residency in the United States prior to 2004 and who published at least one manuscript prior to traditional CT fellowship training were included (n=472). Each surgeon's educational background, work history, and research publications were recorded from publicly-available online sources.RESULTS: In total, 370 surgeons (78.4%) co-authored a CT surgery manuscript before fellowship training, while 102 (21.6%) published only on subjects unrelated to CT surgery. Regardless of whether surgeons pursued dedicated research training or not, those who co-authored a CT surgery manuscript prior to fellowship training published more papers per year as an attending (p<0.01), resulting in more total publications (p<0.01) and a higher H-index (p<0.01) over comparably long careers. Among CT surgeons who did not publish CT surgery research prior to fellowship training, those who co-authored a CT surgery manuscript during fellowship also exhibited enhanced future academic productivity.CONCLUSIONS: Academic CT surgeons who published CT surgery research prior to fellowship training ultimately exhibit more prolific and impactful research profiles compared to those who published only on subjects unrelated to CT surgery during training. Efforts to increase early engagement in CT surgery research among trainees should be fully endorsed.

    View details for DOI 10.1016/j.athoracsur.2020.10.013

    View details for PubMedID 33159869

  • 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

  • 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

  • Endoscopic Radial Artery Harvesting During Anesthesia Line Placement Reduces the Time and Cost of Multivessel Coronary Artery Bypass Grafting. Innovations (Philadelphia, Pa.) Wang, H., Bilbao, M. S., Miller, S. L., O'Donnell, C. T., Boyd, J. H. 2020: 1556984519882014


    OBJECTIVE: Endoscopic radial artery (RA) harvesting performed concurrently with internal mammary artery (IMA) takedown and endoscopic saphenous vein (SV) harvesting creates a crowded and inefficient operating room environment. We assessed the effect of a presternotomy RA harvest strategy on surgery time and costs.METHODS: A total of 41 patients underwent elective, first-time, isolated multivessel on-pump coronary artery bypass grafting including an IMA, RA, and SV graft. The first 20 patients (Phase I) underwent endoscopic RA harvesting concurrently with IMA takedown and endoscopic SV harvesting after sternotomy, requiring two sets of endoscopic harvesting equipment per case, each used by a separate individual. The final 21 patients (Phase II) underwent endoscopic RA harvesting during anesthesia line placement, completing the procedure before sternotomy, thus requiring only one set of endoscopic harvesting equipment reused by a single individual.RESULTS: There were no differences in baseline patient characteristics, number of bypasses, duration of SV or RA harvest time, or duration of cardiopulmonary bypass or cross-clamp time between the two groups. Total surgery time was reduced by 32 minutes in Phase II (P = 0.044). Relative to a total hospital direct cost of 100.00 units, total surgery costs were reduced from 29.33 units in Phase I to 25.62 units in Phase II (P = 0.001). No anesthesia- or RA harvest-related complications occurred in either group.CONCLUSIONS: Endoscopic RA harvesting can be safely performed during anesthesia line placement prior to sternotomy. Our simple but innovative strategy improves intraoperative workflow, reduces the time and cost of surgery, and advances the delivery of high-quality patient care.

    View details for DOI 10.1177/1556984519882014

    View details for PubMedID 31903868

  • In Vivo Validation of Restored Chordal Biomechanics After Mitral Ring Annuloplasty in a Rare Ovine Case of Natural Chronic Functional Mitral Regurgitation. Journal of cardiovascular development and disease Wang, H. n., Paulsen, M. J., Imbrie-Moore, A. M., Tada, Y. n., Bergamasco, H. n., Baker, S. W., Shudo, Y. n., Ma, M. n., Woo, J. Y. 2020; 7 (2)


    Mitral valve chordae tendineae forces are elevated in the setting of mitral regurgitation (MR). Ring annuloplasty is an essential component of surgical repair for MR, but whether chordal forces are reduced after mitral annuloplasty has never been validated in vivo. Here, we present an extremely rare ovine case of natural, severe chronic functional MR, in which we used force-sensing fiber Bragg grating neochordae to directly measure chordal forces in the baseline setting of severe MR, as well as after successful mitral ring annuloplasty repair. Overall, our report is the first to confirm in vivo that mitral ring annuloplasty reduces elevated chordae tendineae forces associated with chronic functional MR.

    View details for DOI 10.3390/jcdd7020017

    View details for PubMedID 32429298

  • Off-Pump Mini Thoracotomy Versus Sternotomy for Left Anterior Descending Myocardial Bridge Unroofing. The Annals of thoracic surgery Wang, H. n., Pargaonkar, V. S., Hironaka, C. E., Bajaj, S. S., Abbot, C. J., O'Donnell, C. T., Miller, S. L., Honda, Y. n., Rogers, I. S., Tremmel, J. A., Fischbein, M. P., Mitchell, R. S., Schnittger, I. n., Boyd, J. H. 2020


    Myocardial bridge (MB) of the left anterior descending (LAD) coronary artery occurs in approximately 25% of the population. For patients with a symptomatic, hemodynamically significant MB who fail medical therapy, MB unroofing represents the optimal surgical management. Here, we evaluated minimally invasive MB unroofing in selected patients compared with sternotomy.MB unroofing was performed in 141 adult patients via sternotomy on-pump (ST-on, n=40), sternotomy off-pump (ST-off, n=62), or mini thoracotomy off-pump (MT, n=39). Angina symptoms were assessed preoperatively and 6-months postoperatively using the Seattle Angina Questionnaire. Matching included all MT patients and 31 ST-off patients with similar MB characteristics, no previous cardiac surgery or coronary interventions, and no concomitant procedures.MT patients tended to have a shorter MB length than ST-on and ST-off patients (2.57 vs 2.93 vs 3.09 cm, p=0.166). ST-on patients had a longer hospital stay than ST-off and MT patients (5.0 vs 4.0 vs 3.0 days, p<0.001), and more blood transfusions (15.2% vs 0.0% vs 2.6%, p=0.002). After matching, MT patients had a shorter hospital stay than ST-off patients (3.0 vs 4.0 days, p=0.005). No deaths or major complications occurred in any group. In all groups, MB unroofing yielded significant symptomatic improvement regarding physical limitation, angina stability, angina frequency, treatment satisfaction, and quality of life.We report the largest experience of off-pump minimally invasive MB unroofing, which may be safely performed in carefully selected patients, yielding dramatic improvements in angina symptomatology at 6 months after surgery.

    View details for DOI 10.1016/j.athoracsur.2020.11.023

    View details for PubMedID 33333083

  • Photosynthetic symbiotic therapy. Aging Wang, H., Wu, M. A., Woo, Y. J. 2019

    View details for PubMedID 30683833

  • A Unique Collateral Artery Development Program Promotes Neonatal Heart Regeneration. Cell Das, S., Goldstone, A. B., Wang, H., Farry, J., D'Amato, G., Paulsen, M. J., Eskandari, A., Hironaka, C. E., Phansalkar, R., Sharma, B., Rhee, S., Shamskhou, E. A., Agalliu, D., de Jesus Perez, V., Woo, Y. J., Red-Horse, K. 2019


    Collateral arteries are an uncommon vessel subtype that can provide alternate blood flow to preserve tissue following vascular occlusion. Some patients with heart disease develop collateral coronary arteries, and this correlates with increased survival. However, it is not known how these collaterals develop or how to stimulate them. We demonstrate that neonatal mouse hearts use a novel mechanism to build collateral arteries in response to injury. Arterial endothelial cells (ECs) migrated away from arteries along existing capillaries and reassembled into collateral arteries, which we termed "artery reassembly". Artery ECs expressed CXCR4, and following injury, capillary ECs induced its ligand, CXCL12. CXCL12 or CXCR4 deletion impaired collateral artery formation and neonatal heart regeneration. Artery reassembly was nearly absent in adults but was induced by exogenous CXCL12. Thus, understanding neonatal regenerative mechanisms can identify pathways that restore these processes in adults and identify potentially translatable therapeutic strategies for ischemic heart disease.

    View details for PubMedID 30686582

  • Bioengineered analog of stromal cell-derived factor 1α preserves the biaxial mechanical properties of native myocardium after infarction. Journal of the mechanical behavior of biomedical materials Wang, H. n., Wisneski, A. n., Paulsen, M. J., Imbrie-Moore, A. n., Wang, Z. n., Xuan, Y. n., Hernandez, H. L., Lucian, H. J., Eskandari, A. n., Thakore, A. D., Farry, J. M., Hironaka, C. E., von Bornstaedt, D. n., Steele, A. N., Stapleton, L. M., Williams, K. M., Wu, M. A., MacArthur, J. W., Woo, Y. J. 2019; 96: 165–71


    Adverse remodeling of the left ventricle (LV) after myocardial infarction (MI) results in abnormal tissue biomechanics and impaired cardiac function, often leading to heart failure. We hypothesized that intramyocardial delivery of engineered stromal cell-derived factor 1α analog (ESA), our previously-developed supra-efficient pro-angiogenic chemokine, preserves biaxial LV mechanical properties after MI. Male Wistar rats (n = 45) underwent sham surgery (n = 15) or permanent left anterior descending coronary artery ligation. Rats sustaining MI were randomized for intramyocardial injections of either saline (100 μL, n = 15) or ESA (6 μg/kg, n = 15), delivered at four standardized borderzone sites. After 4 weeks, echocardiography was performed, and the hearts were explanted. Tensile testing of the anterolateral LV wall was performed using a displacement-controlled biaxial load frame, and modulus was determined after constitutive modeling. At 4 weeks post-MI, compared to saline controls, ESA-treated hearts had greater wall thickness (1.68 ± 0.05 mm vs 1.42 ± 0.08 mm, p = 0.008), smaller end-diastolic LV internal dimension (6.88 ± 0.29 mm vs 7.69 ± 0.22 mm, p = 0.044), and improved ejection fraction (62.8 ± 3.0% vs 49.4 ± 4.5%, p = 0.014). Histologic analysis revealed significantly reduced infarct size for ESA-treated hearts compared to saline controls (29.4 ± 2.9% vs 41.6 ± 3.1%, p = 0.021). Infarcted hearts treated with ESA exhibited decreased modulus compared to those treated with saline in both the circumferential (211.5 ± 6.9 kPa vs 264.3 ± 12.5 kPa, p = 0.001) and longitudinal axes (194.5 ± 6.5 kPa vs 258.1 ± 14.4 kPa, p < 0.001). In both principal directions, ESA-treated infarcted hearts possessed similar tissue compliance as sham non-infarcted hearts. Overall, intramyocardial ESA therapy improves post-MI ventricular remodeling and function, reduces infarct size, and preserves native LV biaxial mechanical properties.

    View details for PubMedID 31035067

  • Use of a supramolecular polymeric hydrogel as an effective post-operative pericardial adhesion barrier. Nature biomedical engineering Stapleton, L. M., Steele, A. N., Wang, H. n., Lopez Hernandez, H. n., Yu, A. C., Paulsen, M. J., Smith, A. A., Roth, G. A., Thakore, A. D., Lucian, H. J., Totherow, K. P., Baker, S. W., Tada, Y. n., Farry, J. M., Eskandari, A. n., Hironaka, C. E., Jaatinen, K. J., Williams, K. M., Bergamasco, H. n., Marschel, C. n., Chadwick, B. n., Grady, F. n., Ma, M. n., Appel, E. A., Woo, Y. J. 2019; 3 (8): 611–20


    Post-operative adhesions form as a result of normal wound healing processes following any type of surgery. In cardiac surgery, pericardial adhesions are particularly problematic during reoperations, as surgeons must release the adhesions from the surface of the heart before the intended procedure can begin, thereby substantially lengthening operation times and introducing risks of haemorrhage and injury to the heart and lungs during sternal re-entry and cardiac dissection. Here we show that a dynamically crosslinked supramolecular polymer-nanoparticle hydrogel, with viscoelastic and flow properties that enable spraying onto tissue as well as robust tissue adherence and local retention in vivo for two weeks, reduces the formation of pericardial adhesions. In a rat model of severe pericardial adhesions, the hydrogel markedly reduced the severity of the adhesions, whereas commercial adhesion barriers (including Seprafilm and Interceed) did not. The hydrogels also reduced the severity of cardiac adhesions (relative to untreated animals) in a clinically relevant cardiopulmonary-bypass model in sheep. This viscoelastic supramolecular polymeric hydrogel represents a promising clinical solution for the prevention of post-operative pericardial adhesions.

    View details for DOI 10.1038/s41551-019-0442-z

    View details for PubMedID 31391596

  • Scimitar Syndrome in Children and Adults: Natural History, Outcomes, and Risk Analysis. The Annals of thoracic surgery Wang, H., Kalfa, D., Rosenbaum, M. S., Ginns, J. N., Lewis, M. J., Glickstein, J. S., Bacha, E. A., Chai, P. J. 2018; 105 (2): 592-598


    Scimitar syndrome involves congenital anomalous pulmonary venous return to the inferior vena cava. Optimal management remains controversial. We describe the natural history of disease, nonsurgical and surgical outcomes, and risk factors for poor outcomes at our institution.Patients with anomalous pulmonary venous return to the inferior vena cava documented on echocardiography at our institution between January 1994 and January 2015 were reviewed retrospectively. The study protocol IRB-AAAO1805 was approved.Forty-seven patients were identified, including 20 infants with significant associated congenital heart defects (42.6%, including 7 with single ventricle physiology), and 10 infants (21.3%) and 16 noninfants (34.0%) with isolated scimitar syndrome. Median follow-up was 3.55 years. Noninfants exhibited lower incidences of right pulmonary artery hypoplasia (p < 0.001), aortopulmonary collaterals (p = 0.004), and scimitar vein obstruction at the caval confluence (p = 0.032). Eighteen patients (38.3%) underwent surgical repair for scimitar syndrome. Overall mortality after baffle repair or scimitar vein reimplantation was 37.5% (3 of 8) for infants and 0% (0 of 6) for noninfants (p = 0.209). Overall mortality for medically managed infants was 46.7% (7 of 15) compared with 0% (0 of 8) for noninfants (p = 0.052). Multivariable analyses identified infantile onset as an independent risk factor for stenosis or obstruction after repair (hazard ratio 9.34, p = 0.048), and single ventricle physiology as an independent risk factor for mortality among unrepaired patients (hazard ratio 29.8, p = 0.004).The severity of scimitar syndrome depends on presenting age and associated congenital heart disease. Nonsurgical and surgical outcomes are suboptimal for infantile disease, which is a risk factor for stenosis after repair. Single ventricle physiology is associated with poor prognosis.

    View details for DOI 10.1016/j.athoracsur.2017.06.061

    View details for PubMedID 29054305

  • Structural, angiogenic, and immune responses influencing myocardial regeneration: a glimpse into the crucible. NPJ Regenerative medicine Baccouche, B. M., Elde, S., Wang, H., Woo, Y. J. 2024; 9 (1): 18


    Complete cardiac regeneration remains an elusive therapeutic goal. Although much attention has been focused on cardiomyocyte proliferation, especially in neonatal mammals, recent investigations have unearthed mechanisms by which non-cardiomyocytes, such as endothelial cells, fibroblasts, macrophages, and other immune cells, play critical roles in modulating the regenerative capacity of the injured heart. The degree to which each of these cell types influence cardiac regeneration, however, remains incompletely understood. This review highlights the roles of these non-cardiomyocytes and their respective contributions to cardiac regeneration, with emphasis on natural heart regeneration after cardiac injury during the neonatal period.

    View details for DOI 10.1038/s41536-024-00357-z

    View details for PubMedID 38688935

    View details for PubMedCentralID 4243683

  • Large Animal Translational Validation of 3 Mitral Valve Repair Operations for Mitral Regurgitation Using a Mitral Valve Prolapse Model: A Comprehensive In Vivo Biomechanical Engineering Analysis. Circulation. Cardiovascular interventions Zhu, Y., Yajima, S., Park, M. H., Venkatesh, A., Stark, C. J., Tran, N. A., Walsh, S. K., Ethiraj, S., Wilkerson, R. J., Lin, L. E., Lee, S. H., Gates, K. Y., Arthur, J. D., Baker, S. W., Mullis, D. M., Wu, C. A., Harima, S., Pokhrel, B., Resuello, D., Bergamasco, H., Wu, M. A., Baccouche, B. M., Pandya, P. K., Elde, S., Wang, H., Woo, Y. J. 2024; 17 (4): e013196


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

    View details for DOI 10.1161/CIRCINTERVENTIONS.123.013196

    View details for PubMedID 38626077

  • Stromal cell-derived factor-1 alpha improves cardiac function in a novel diet-induced coronary atherosclerosis model, the SR-B1ΔCT/LDLR KO mouse. Atherosclerosis Mullis, D. M., Padilla-Lopez, A., Wang, H., Zhu, Y., Elde, S., Bonham, S. A., Yajima, S., Kocher, O. N., Krieger, M., Woo, Y. J. 2024: 117518


    There are a limited number of pharmacologic therapies for coronary artery disease, and few rodent models of occlusive coronary atherosclerosis and consequent myocardial infarction with which one can rapidly test new therapeutic approaches. Here, we characterize a novel, fertile, and easy-to-use HDL receptor (SR-B1)-based model of atherogenic diet-inducible, fatal coronary atherosclerosis, the SR-B1ΔCT/LDLR KO mouse. Additionally, we test intramyocardial injection of Stromal Cell-Derived Factor-1 alpha (SDF-1α), a potent angiogenic cytokine, as a possible therapy to rescue cardiac function in this mouse.SR-B1ΔCT/LDLR KO mice were fed the Paigen diet or standard chow diet, and we determined the effects of the diets on cardiac function, histology, and survival. After two weeks of feeding either the Paigen diet (n = 24) or standard chow diet (n = 20), the mice received an intramyocardial injection of either SDF-1α or phosphate buffered saline (PBS). Cardiac function and angiogenesis were assessed two weeks later.When six-week-old mice were fed the Paigen diet, they began to die as early as 19 days later and 50% had died by 38 days. None of the mice maintained on the standard chow diet died by day 72. Hearts from mice on the Paigen diet showed evidence of cardiomegaly, myocardial infarction, and occlusive coronary artery disease. For the five mice that survived until day 28 that underwent an intramyocardial injection of PBS on day 15, the average ejection fraction (EF) decreased significantly from day 14 (the day before injection, 52.1 ± 4.3%) to day 28 (13 days after the injection, 30.6 ± 6.8%) (paired t-test, n = 5, p = 0.0008). Of the 11 mice fed the Paigen diet and injected with SDF-1α on day 15, 8 (72.7%) survived to day 28. The average EF for these 8 mice increased significantly from 48.2 ± 7.2% on day 14 to63.6 ± 6.9% on day 28 (Paired t-test, n = 8, p = 0.003).This new mouse model and treatment with the promising angiogenic cytokine SDF-1α may lead to new therapeutic approaches for ischemic heart disease.

    View details for DOI 10.1016/j.atherosclerosis.2024.117518

    View details for PubMedID 38627162

  • Beating Heart Transplant Procedures Using Organs From Donors With Circulatory Death. JAMA network open Krishnan, A., Ruaengsri, C., Guenthart, B. A., Shudo, Y., Wang, H., Ma, M. R., MacArthur, J. W., Hiesinger, W., Woo, Y. J. 2024; 7 (3): e241828


    The use of ex vivo normothermic organ perfusion has enabled the use of deceased after circulatory death (DCD) donors for heart transplants. However, compared with conventional brain death donation, DCD heart transplantation performed with ex vivo organ perfusion involves an additional period of warm and cold ischemia, exposing the allograft to multiple bouts of ischemia reperfusion injury and may contribute to the high rates of extracorporeal membrane oxygenation usage after DCD heart transplantation.To assess whether the beating heart method of DCD heart transplantation is safe and whether it has an acceptable rate of extracorporeal membrane oxygenation use postoperatively.This case series includes 10 patients with end-stage heart failure undergoing DCD heart transplantation at a single academic medical center from October 1, 2022, to August 3, 2023. Data were analyzed from October 2022 to August 2023.Using a beating heart method of implantation of the donor allograft.The main outcome was primary graft dysfunction necessitating postoperative initiation of mechanical circulatory support. Survival and initiation of mechanical circulatory support were secondary outcomes.In this case series, 10 consecutive patients underwent DCD heart transplantation via the beating heart method. Ten of 10 recipients were male (100%), the mean (SD) age was 51.2 (13.8) years, and 7 (70%) had idiopathic dilated cardiomyopathy. Ten patients (100%) survived, and 0 patients had initiation of extracorporeal membrane oxygenation postoperatively. No other mechanical circulatory support, including intra-aortic balloon pump, was initiated postoperatively. Graft survival was 100% (10 of 10 patients), and, at the time of publication, no patients have been listed for retransplantation.In this study of 10 patients undergoing heart transplantation, the beating heart implantation method for DCD heart transplantation was safe and may mitigate ischemia reperfusion injury, which may lead to lower rates of primary graft dysfunction necessitating extracorporeal membrane oxygenation. These results are relevant to institutions using DCD donors for heart transplantation.

    View details for DOI 10.1001/jamanetworkopen.2024.1828

    View details for PubMedID 38466306

  • Four Decades of Progress in Heart-Lung Transplantation: 271 Cases at a Single Institution. The Journal of thoracic and cardiovascular surgery Elde, S., Baccouche, B. M., Mullis, D. M., Leipzig, M. M., Deuse, T., Krishnan, A., Fawad, M., Dale, R., Walsh, S., Padilla-Lopez, A., Wesley, B., He, H., Yajima, S., Zhu, Y., Wang, H., Guenthart, B. A., Shudo, Y., Reitz, B. A., Woo, Y. J. 2024


    OBJECTIVE: The objective of this study is to evaluate survival for combined heart-lung transplant (HLTx) recipients across four decades at a single institution. We aim to summarize our contemporary practice based upon more than 271 HLTx over 40 years.METHODS: Data were collected from a departmental database and the United Network for Organ Sharing (UNOS). Recipients <18y, those undergoing redo HLTx , or triple-organ system transplantation were excluded, leaving 271 patients for analysis. The Pioneering Era was defined by date of transplant between 1981-2000 (N=155), and the Modern Era between 2001-2022 (N=116). Survival analysis was performed using cardinality matching of populations based on donor and recipient age, donor and recipient sex, ischemic time, and sex-matching.RESULTS: Between 1981-2022, 271 HLTx were performed at a single institution. Recipients in the Modern Era were older (42 vs 34y, P<0.001) and had shorter waitlist times (78 vs 234d, P<0.001). Allografts from female donors were more common in the Modern Era (59% vs 39%, P=0.002). In the matched survival analysis, 30-day survival (97% vs 84%, P=0.005), 1-year survival (89% vs 77%, P=0.041), and 10-year survival (53% vs 26%, P=0.012) significantly improved in the Modern Era relative to the Pioneering Era, respectively.CONCLUSIONS: Long-term survival in HLTx is achievable with institutional experience and may continue to improve in the coming decades. Advances in mechanical circulatory support, improved maintenance immunosuppression, and early recognition and management of acute complications such as primary graft dysfunction and acute rejection have dramatically improved the prognosis for HLTx recipients in our contemporary institutional experience.

    View details for DOI 10.1016/j.jtcvs.2024.01.042

    View details for PubMedID 38320627

  • Redo aortic valve replacement for an incorrectly sized rapid deployment valve. JTCVS techniques Zhu, Y., Wang, H., Kim, J. B., Woo, Y. J. 2024; 23: 18-20

    View details for DOI 10.1016/j.xjtc.2023.10.029

    View details for PubMedID 38352018

    View details for PubMedCentralID PMC10859641

  • Electrophysiological mapping of the epicardium via 3D-printed flexible arrays. Bioengineering & translational medicine Pong, T., Cyr, K. J., Carlton, C., Aparicio-Valenzuela, J., Wang, H., Babakhanian, M., Maiuolo, A., Lucian, H., Wang, P. J., Woo, Y. J., Lee, A. M. 2023; 8 (6): e10575


    Cardiac electrophysiology mapping and ablation are widely used to treat heart rhythm disorders such as atrial fibrillation (AF) and ventricular tachycardia (VT). Here, we describe an approach for rapid production of three dimensional (3D)-printed mapping devices derived from magnetic resonance imaging. The mapping devices are equipped with flexible electronic arrays that are shaped to match the epicardial contours of the atria and ventricle and allow for epicardial electrical mapping procedures. We validate that these flexible arrays provide high-resolution mapping of epicardial signals in vivo using porcine models of AF and myocardial infarction. Specifically, global coverage of the epicardial surface allows for mapping and ablation of myocardial substrate and the capture of premature ventricular complexes with precise spatial-temporal resolution. We further show, as proof-of-concept, the localization of sites of VT by means of beat-to-beat whole-chamber ventricular mapping of ex vivo Langendorff-perfused human hearts.

    View details for DOI 10.1002/btm2.10575

    View details for PubMedID 38023702

    View details for PubMedCentralID PMC10658567

  • Dedifferentiation and Proliferation of Artery Endothelial Cells Drive Coronary Collateral Development in Mice. Arteriosclerosis, thrombosis, and vascular biology Arolkar, G., Krishna Kumar, S., Wang, H., Gonzalez, K. M., Kumar, S., Bishnoi, B., Rios Coronado, P. E., Woo, Y. J., Red-Horse, K., Das, S. 2023


    BACKGROUND: Collateral arteries act as natural bypasses which reroute blood flow to ischemic regions and facilitate tissue regeneration. In an injured heart, neonatal artery endothelial cells orchestrate a systematic series of cellular events, which includes their outward migration, proliferation, and coalescence into fully functional collateral arteries. This process, called artery reassembly, aids complete cardiac regeneration in neonatal hearts but is absent in adults. The reason for this age-dependent disparity in artery cell response is completely unknown. In this study, we investigated if regenerative potential of coronary arteries is dictated by their ability to dedifferentiate.METHODS: Single-cell RNA sequencing of coronary endothelial cells was performed to identify differences in molecular profiles of neonatal and adult endothelial cells in mice. Findings from this in silico analyses were confirmed with in vivo experiments using genetic lineage tracing, whole organ immunostaining, confocal imaging, and cardiac functional assays in mice.RESULTS: Upon coronary occlusion, neonates showed a significant increase in actively cycling artery cells and expressed prominent dedifferentiation markers. Data from in silico pathway analyses and in vivo experiments suggested that upon myocardial infarction, cell cycle reentry of preexisting neonatal artery cells, the subsequent collateral artery formation, and recovery of cardiac function are dependent on arterial VegfR2 (vascular endothelial growth factor receptor-2). This subpopulation of dedifferentiated and proliferating artery cells was absent in nonregenerative postnatal day 7 or adult hearts.CONCLUSIONS: These data indicate that adult artery endothelial cells fail to drive collateral artery development due to their limited ability to dedifferentiate and proliferate.

    View details for DOI 10.1161/ATVBAHA.123.319319

    View details for PubMedID 37345524

  • First-in-human beating-heart transplant. JTCVS techniques Krishnan, A., Kasinpila, P., Wang, H., Ruaengsri, C., Shudo, Y., Jackson, E., Woo, Y. J. 2023; 19: 80-85

    View details for DOI 10.1016/j.xjtc.2023.02.015

    View details for PubMedID 37324334

    View details for PubMedCentralID PMC10267812

  • 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

  • Strategies for Transcatheter Aortic Valve Replacement in Patients With a Right Aortic Arch. Structural heart : the journal of the Heart Team Wang, H., Akanbi, O., MacArthur, J. W., Sharma, R. P. 2023; 7 (2): 100099

    View details for DOI 10.1016/j.shj.2022.100099

    View details for PubMedID 37275589

    View details for PubMedCentralID PMC10236863

  • 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

  • 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

  • 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

  • Impact of PhD Degree Versus Non-PhD Research Fellowship on Future Research Productivity Among Academic Cardiothoracic Surgeons. World journal of surgery Bajaj, S. S., Wang, H., Williams, K. M., Heiler, J. C., Pickering, J. M., Manjunatha, K., O'Donnell, C. T., Sanchez, M., Boyd, J. H. 2022


    BACKGROUND: A PhD degree can offer significant research experience, but previous studies yielded conflicting conclusions on the relationship between a PhD degree and future research output. We compared the impact of a PhD degree versus research fellowship(RF) training on research productivity in cardiothoracic surgeons, hypothesizing that training pathways may influence potential associations.METHODS: CT surgeons practicing at all accredited United States CT surgery training programs in 2018 who pursued dedicated time for research (n=597), including earning a PhD degree (n=92) or completing a non-PhD RF (n=505), were included. To control for training pathways, we performed subanalyses of U.S. medical school graduates (n=466) and international medical school graduates (IMGs) (n=131). Surgeon-specific data were obtained from publicly available sources (e.g., institutional webpages, Scopus).RESULTS: PhD surgeons published greater total papers (68.5 vs. 52.0, p=0.0179) and total papers per year as an attending (4.6 vs. 3.0, p=0.0150). For U.S. medical school graduates, there were 40 PhD surgeons and 426 non-PhD RF surgeons; both groups published a similar number of total papers (64.5 vs. 54.0, p=0.3738) and total papers per year (3.2 vs. 3.0, p=0.7909). For IMGs, there were 52 PhD surgeons and 79 non-PhD RF surgeons; the PhD surgeons published greater total papers (80.5 vs. 45.0, p=0.0101) and total papers per year (5.7 vs. 2.7, p=0.0037).CONCLUSION: CT surgeons with dedicated research training are highly academically productive. Although a PhD degree may be associated with enhanced career-long research productivity for IMGs, this association was not observed for U.S. medical school graduates.

    View details for DOI 10.1007/s00268-022-06661-3

    View details for PubMedID 35871657

  • 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

  • An automated line-clearing chest tube system after cardiac surgery. JTCVS open Obafemi, O. O., Wang, H., Bajaj, S. S., O'Donnell, C. T., Elde, S., Boyd, J. H. 2022; 10: 246-253


    To complete the first in-human study of the automated line clearance Thoraguard chest tube system. The study focuses on the viability and efficacy of the device in comparison with conventional models as well as secondary matters such as patient experience and ease of use.This was a single-center, prospective, open-label study involving adult patients (n = 27) who underwent nonemergent, first-time, cardiac surgery. Patients received automated clearance chest tubes for surgical drainage in both the mediastinal and pleural spaces. The control group was retrospective (n = 80); individuals received conventional chest tubes placed and secured in locations determined at the surgeon's discretion.The automated-clearance tubes exhibited a similar drainage profile at 1, 3, 6, 12, and 24 hours compared with the conventional chest tubes. The final output at the time of tube removal was also similar (1150 [750-1590] vs 1289 [766.3-1890] mL, respectively, P = .76). The number of patients readmitted for drainage of an effusion was similar in both groups (1/27 [3.7%] vs 3/80 [3.75%], P > .99).This study has shown that the Centese Thoraguard chest tube system is a viable option for surgical chest drainage and effective when used in routine cardiac surgery operations.

    View details for DOI 10.1016/j.xjon.2022.02.020

    View details for PubMedID 36004272

    View details for PubMedCentralID PMC9390781

  • Career Progression and Research Productivity of Women in Academic Cardiothoracic Surgery. The Annals of thoracic surgery Williams, K. M., Wang, H., Bajaj, S. S., Hironaka, C. E., Kasinpila, P., O'Donnell, C. T., Sanchez, M., Watkins, A. C., Lui, N. S., Backhus, L. M., Boyd, J. 2022


    The objective of this work was to delineate career progression and research productivity of women practicing cardiothoracic surgery in the academic setting.Cardiothoracic surgeons at the 79 accredited U.S. cardiothoracic surgery training programs in 2020 were included in this cross-sectional analysis. Data regarding sub-specialization, training, practice history, and publications were gathered from public sources including department websites, CTSNet, and Scopus.A total of 1065 surgeons (51.3% cardiac, 32.1% thoracic, 16.6% congenital) were identified. Women accounted for 10.6% (113) of the population (7.9% of cardiac, 15.5% of thoracic, 9.6% of congenital surgeons). The median number of cardiothoracic surgeons per institution was 12 [IQR 10-17], with a median of one woman [IQR 0-2]. Fifteen of 79 (19%) programs had zero women. Among women faculty, 5.3% were clinical instructors, 51.3% were assistant professors, 23.0% were associate professors, 16.8% were full professors, and 3.5% had unspecified titles (vs. 2.0%, 32.9%, 23.0%, 37.5%, and 4.6% among men, respectively, p<0.001). Women and men authored a comparable number of first-author (0.4 [0.0-1.3] vs. 0.5 [0.0-1.1], p=0.56) publications per year, but fewer last-author (0.1 [0.0-0.7] vs. 0.4 [0.0-1.3], p<0.0001) and total publications per year (2.7 [1.0-6.2] vs. 3.7 [1.3-7.8], p=0.05) than men. H-index was lower for women than for men overall (8.0 [3.0-15.0] vs. 15.0 [7.0-28.0], p<0.001), but was similar between men and women who had been practicing for 10-20 years.Gender disparities persist in academic cardiothoracic surgery. Efforts should be made to support women in achieving senior roles and academic productivity.

    View details for DOI 10.1016/j.athoracsur.2022.04.057

    View details for PubMedID 35643331

  • Integration of Reinforcement Learning in a Virtual Robotic Surgical Simulation. Surgical innovation Bourdillon, A. T., Garg, A., Wang, H., Woo, Y. J., Pavone, M., Boyd, J. 2022: 15533506221095298


    Background. The revolutions in AI hold tremendous capacity to augment human achievements in surgery, but robust integration of deep learning algorithms with high-fidelity surgical simulation remains a challenge. We present a novel application of reinforcement learning (RL) for automating surgical maneuvers in a graphical simulation.Methods. In the Unity3D game engine, the Machine Learning-Agents package was integrated with the NVIDIA FleX particle simulator for developing autonomously behaving RL-trained scissors. Proximal Policy Optimization (PPO) was used to reward movements and desired behavior such as movement along desired trajectory and optimized cutting maneuvers along the deformable tissue-like object. Constant and proportional reward functions were tested, and TensorFlow analytics was used to informed hyperparameter tuning and evaluate performance.Results. RL-trained scissors reliably manipulated the rendered tissue that was simulated with soft-tissue properties. A desirable trajectory of the autonomously behaving scissors was achieved along 1 axis. Proportional rewards performed better compared to constant rewards. Cumulative reward and PPO metrics did not consistently improve across RL-trained scissors in the setting for movement across 2 axes (horizontal and depth).Conclusion. Game engines hold promising potential for the design and implementation of RL-based solutions to simulated surgical subtasks. Task completion was sufficiently achieved in one-dimensional movement in simulations with and without tissue-rendering. Further work is needed to optimize network architecture and parameter tuning for increasing complexity.

    View details for DOI 10.1177/15533506221095298

    View details for PubMedID 35503302

  • 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

  • Analyzing the Scholarly Impact of Cardiothoracic Surgery Research Using the Relative Citation Ratio. The Journal of surgical research Wang, H., Bajaj, S. S., Williams, K. M., O'Donnell, C. T., Heiler, J. C., Krishnan, A., Pickering, J. M., Sanchez, M., Manjunatha, K., Kumar, S. S., Yu, M. M., Boyd, J. H. 2022; 275: 265-272


    INTRODUCTION: The National Institutes of Health (NIH) recently developed the relative citation ratio (RCR), calculated as article citations benchmarked to NIH-funded publications in the same field. Here, we characterized the scholarly impact of academic cardiothoracic (CT) surgeons and their research using the RCR.MATERIALS AND METHODS: Using a database of 992 CT surgeons, we calculated the RCR for all articles published by each surgeon since 1980 using the NIH iCite database. All data were collected from publicly available online sources. Data are presented as median (interquartile range) or as odds ratios (ORs) for multivariable logistic regression analysis.RESULTS: Where RCR 1.00 indicates equal impact as an NIH-funded publication, the RCR among all 37,402 CT surgery articles was 0.84 (0.33-1.83) and the RCR among NIH-funded CT surgery articles was 1.07 (0.53-2.17). CT surgeons exhibited a career median RCR of 0.82 (0.54-1.13) and maximum RCR of 6.20 (3.04-13.57). Predictors of career median RCR >1.00 included female gender (OR 2.23, P=0.001), thoracic subspecialization (OR 2.50, P<0.001), full professor rank (OR 1.89, P=0.001), and NIH funding (OR 1.75, P=0.001). Predictors of career maximum RCR >50th percentile among CT surgeons included male gender (OR 1.87, P=0.030), thoracic subspecialization (OR 2.05, P<0.001), full professor rank (OR 4.89, P<0.001), NIH funding (OR 3.17, P<0.001), and career duration (OR 1.03, P=0.002).CONCLUSIONS: We present the first assessment of the NIH-validated RCR for academic CT surgery. CT surgery research is highly impactful, although gender disparities persist with respect to the highest-impact research of our specialty.

    View details for DOI 10.1016/j.jss.2022.02.007

    View details for PubMedID 35306262

  • Colocalization of Coronary Plaque with Wall Shear Stress in Myocardial Bridge Patients. Cardiovascular engineering and technology Khan, M. O., Nishi, T., Imura, S., Seo, J., Wang, H., Honda, Y., Nieman, K., Rogers, I. S., Tremmel, J. A., Boyd, J., Schnittger, I., Marsden, A. 2022


    PURPOSE: Patients with myocardial bridges (MBs) have a higher prevalence of atherosclerosis. Wall shear stress (WSS) has previously been correlated with plaque in coronary artery disease patients, but such correlations have not been investigated in symptomatic MB patients. The aim of this paper was to use a multi-scale computational fluid dynamics (CFD) framework to simulate hemodynamics in MB patient, and investigate the co-localization of WSS and plaque.METHODS: We identified N = 10 patients from a previously reported cohort of 50 symptomatic MB patients, all of whom had plaque in the proximal vessel. Dynamic 3D models were reconstructed from coronary computed tomography angiography (CCTA), intravascular ultrasound (IVUS) and catheter angiograms. CFD simulations were performed to compute WSS proximal to, within and distal to the MB. Plaque was quantified from IVUS images in 2 mm segments and registered to CFD model. Plaque area was compared to absolute and patient-normalized WSS.RESULTS: WSS was lower in the proximal segment compared to the bridge segment (6.1 ± 2.9 vs. 16.0 ± 7.1 dynes/cm2, p value < 0.01). Plaque area and plaque burden measured from IVUS peaked at 1-3 cm proximal to the MB entrance, coinciding with the first diagonal branch. Normalized WSS showed a statistically significant moderate correlation with plaque area (r = 0.41, p < 0.01).CONCLUSION: WSS may be obtained non-invasively in MB patients and provides a surrogate marker of plaque area. Using CFD, it may be possible to non-invasively assess the extent of plaque area, and identify patients who could benefit from frequent monitoring or medical management.

    View details for DOI 10.1007/s13239-022-00616-4

    View details for PubMedID 35296987

  • Biomechanical Analysis of the Ross Procedure in an Ex Vivo Left Heart Simulator. World journal for pediatric & congenital heart surgery Bryan, A. Y., Brandon Strong, E., Kidambi, S., Gilligan-Steinberg, S., Bennett-Kennett, R., Lee, J. Y., Imbrie-Moore, A., Moye, S. C., Hendrickx-Rodriguez, S., Wang, H., Dauskardt, R. H., Joseph Woo, Y., Ma, M. R. 2022; 13 (2): 166-174


    BACKGROUND: Neo-aortic pulmonary autografts often experience root dilation and valve regurgitation over time. This study seeks to understand the biomechanical differences between aortic and neo-aortic pulmonary roots using a heart simulator.METHODS: Porcine aortic, neo-aortic pulmonary, and pulmonary roots (n=6) were mounted in a heart simulator (parameters: 100 mm Hg, 37 °C, 70 cycles per minute, 5.0 L/min cardiac output). Echocardiography was used to study root distensibility (percentage change in luminal diameter between systole and diastole) and valve function. Leaflet motion was tracked with high-speed videography. After 30 min in the simulator, leaflet thickness (via cryosectioning), and multiaxial modulus (via lenticular hydrostatic deformation testing) were obtained.RESULTS: There were no significant differences between aortic and neo-aortic pulmonary leaflet motion, including mean opening velocity (218 vs 248 mm/s, P=.27) or mean closing velocity (116 vs 157 mm/s, P=.12). Distensibility was similar between aortic (8.5%, 1.56 mm) and neo-aortic pulmonary (7.8%, 1.12 mm) roots (P=.59). Compared to virgin controls, native pulmonic roots exposed to systemic pressure for 30 min had reduced leaflet thickness (630 vs 385 m, P=.049) and a reduced Young's modulus (3,125 vs 1,089 kPa, P=.077). In contrast, the aortic roots exposed to pressure displayed no significant difference in aortic leaflet thickness (1,317 vs 1,256 m, P=.27) or modulus (5,931 vs 3,631 kPa, P=.56).CONCLUSIONS: Neo-aortic pulmonary roots demonstrated equivalence in valve function and distensibility but did experience changes in biomechanical properties and morphology. These changes may contribute to long-term complications associated with the Ross procedure.

    View details for DOI 10.1177/21501351211070288

    View details for PubMedID 35238706

  • 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

  • Applications of Tissue Decellularization Techniques in Ventricular Myocardial Biofabrication. Frontiers in bioengineering and biotechnology Krishnan, A., Wang, H., MacArthur, J. W. 2022; 10: 802283


    Ischemic heart disease is the leading cause of death around the world, and though the advent of coronary revascularization has revolutionized its treatment, many patients who sustain ischemic injury to the heart will go on to develop heart failure. Biofabrication of ventricular myocardium for replacement of irreversibly damaged ischemic myocardium is sought after as a potential therapy for ischemic heart failure, though challenges in reliably producing this biomaterial have limited its clinical application. One method that shows promise for generation of functional myocardium is the use of tissue decellularization to serve as a scaffold for biofabrication. This review outlines the methods, materials, challenges, and prospects of tissue decellularization techniques for ventricular myocardium biofabrication. Decellularization aims to preserve the architecture and composition of the extracellular matrix of the tissue it is applied to, allowing for the subsequent implantation of stem cells of the desired cell type. Decellularization can be achieved with multiple reagents, most of which have detergent properties. A variety of cell types can be implanted in the resulting scaffold, including cardiac progenitor cells, and embryonic or induced pluripotent stem cells to generate a range of tissue, from patches to beating myocardium. The future of this biofabrication method will likely emphasize patient specific tissue engineering to generate complex 3-dimensional constructs that can replace dysfunctional cardiac structures.

    View details for DOI 10.3389/fbioe.2022.802283

    View details for PubMedID 35265593

  • Analysis of the revised heart allocation policy and the influence of increased mechanical circulatory support on survival. The Journal of thoracic and cardiovascular surgery Elde, S., He, H., Lingala, B., Baiocchi, M., Wang, H., Hiesinger, W., MacArthur, J. W., Shudo, Y., Woo, Y. J. 1800


    OBJECTIVES: In 2018, the new United Network for Organ Sharing heart allocation policy took effect. This study evaluated waitlist mortality, mechanical circulatory support utilization, and its influence on posttransplant survival.METHODS: Two 12-month cohorts matched for time of year before and after the policy change were defined by inclusion criteria of first-time transplant recipients aged 18years or older who were listed and underwent transplant during the same era. Student t test and Wilcoxon rank-sum test were used for mean and median differences, respectively. Categorical variables were compared using chi2 or Fisher exact test. Kaplan-Meier curves were used to characterize survival, including time-to-event analysis with the log-rank test. Fine-Gray modeling was used to characterize waitlist mortality. Cox proportional-hazard models were used for multivariate analysis.RESULTS: Waitlist mortality in the new era is significantly improved based on a competing-risks model (Gray test P=.0064). Unadjusted 180-day posttransplant mortality increased from 5.8% during the old era to 8.0% during the new (P=.0134). However, time-to-event analysis showed similar 180-day survival in both eras. After risk adjustment, the hazard ratio for posttransplant 180-day mortality during the new era was 1.18 (95% CI, 0.85-1.64; P=.333). The posttransplant 180-day mortality of the extracorporeal membrane oxygenation bridge-to-transplant subgroup improved from 28.6% in the old era to 8.4% in the new era (P=.0103; log-rank P=.0021). Patients with an intra-aortic balloon pump at the time of transplant had similar 180-day posttransplant mortality between eras (5.4% vs 7.0%; P=.4831).CONCLUSIONS: The United Network for Organ Sharing policy change is associated with reduced waitlist mortality and similar risk adjusted posttransplant 180-day mortality. The new era is also associated with improved 180-day survival in patientsundergoing bridge to transplant with extracorporeal membrane oxygenation.

    View details for DOI 10.1016/j.jtcvs.2021.11.076

    View details for PubMedID 35027214

  • 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

  • The Academic Impact of Advanced Clinical Fellowship Training among General Thoracic Surgeons. Journal of surgical education Patel, D. C., Wang, H., Bajaj, S. S., Williams, K. M., Pickering, J. M., Heiler, J. C., Manjunatha, K., O'Donnell, C. T., Sanchez, M., Boyd, J. H., Backhus, L. M. 2021


    OBJECTIVE: Advanced clinical fellowship training has become a popular option for surgical trainees seeking to bolster their clinical training and expertise. However, the long-term academic impact of this additional training following a traditional thoracic surgery fellowship is unknown. This study aimed to delineate the impact of an advanced clinical fellowship on subsequent research productivity and advancement in academic career among general thoracic surgeons.METHODS: Using an internally constructed database of active, academic general thoracic surgeons who are current faculty at accredited cardiothoracic surgery training programs within the United States, surgeons were dichotomized according to whether an advanced clinical fellowship was completed or not. Academic career metrics measured by research productivity, scholarly impact (H-index), funding by the National Institutes of Health, and academic rank were compared.RESULTS: Among 285 general thoracic surgeons, 89 (31.2%) underwent an advanced fellowship, whereas 196 (68.8%) did not complete an advanced fellowship. The most commonly pursued advanced fellowship was minimally invasive thoracic surgery (32.0%). There were no differences between the two groups in terms of gender, international medical training, or postgraduate education. Those who completed an advanced clinical fellowship were less likely to have completed a dedicated research fellowship compared to those who had not completed any additional clinical training (58.4% vs. 74.0%, p = 0.0124). Surgeons completing an advanced clinical fellowship demonstrated similar cumulative first-author publications (p = 0.4572), last-author publications (p = 0.7855), H-index (p = 0.9651), National Institutes of Health funding (p = 0.7540), and years needed to advance to associate professor (p = 0.3410) or full rank professor (p = 0.1545) compared to surgeons who did not complete an advanced fellowship. These findings persisted in sub-analyses controlling for surgeons completing a dedicated research fellowship.CONCLUSIONS: Academic general thoracic surgeons completing an advanced clinical fellowship demonstrate similar research output and ascend the academic ladder at a similar pace as those not pursuing additional training.

    View details for DOI 10.1016/j.jsurg.2021.09.003

    View details for PubMedID 34674980

  • Impact of Diastolic Vessel Restriction on Quality of Life in Symptomatic Myocardial Bridging Patients Treated With Surgical Unroofing: Preoperative Assessments With Intravascular Ultrasound and Coronary Computed Tomography Angiography. Circulation. Cardiovascular interventions Hashikata, T., Honda, Y., Wang, H., Pargaonkar, V. S., Nishi, T., Hollak, M. B., Rogers, I. S., Nieman, K., Yock, P. G., Fitzgerald, P. J., Schnittger, I., Boyd, J. H., Tremmel, J. A. 2021; 14 (10): e011062


    [Figure: see text].

    View details for DOI 10.1161/CIRCINTERVENTIONS.121.011062

    View details for PubMedID 34665656

  • 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

  • Characterization of academic cardiothoracic surgeons who started as attendings in private or community practice. Surgery Bajaj, S. S., Wang, H., Williams, K. M., Krishnan, A., Heiler, J. C., Pickering, J. M., Manjunatha, K., O'Donnell, C. T., Sanchez, M., Boyd, J. H. 2021


    BACKGROUND: Surgeons are traditionally categorized as working either in academic or private/community practice, but some transition between the two environments. Here, we profile current academic cardiothoracic surgeons who began their attending careers in private or community practice. We hypothesized that research activity may distinguish cardiothoracic surgeons who started in non-academic versus academic practice.METHODS: Publicly available data regarding professional history and research productivity were collected for 992 academic cardiothoracic surgeons on faculty at the 77 cardiothoracic surgery training programs in the United States in 2018. Data are presented as medians analyzed with the Mann-Whitney test or proportions analyzed with Fisher exact test or the chi2 test.RESULTS: A total of 80 (8.1%) academic cardiothoracic surgery faculty started their careers in non-academic practice, and 912 (91.9%) started directly in academia. Those who started in non-academic practice spent a median 7.0 y in private/community practice and were more likely to be cardiac surgeons (68.8% vs 51.6%, P= .0132). They were equally likely to pursue a protected research fellowship (56.3% vs 57.0%, P= .9067) and publish research during training (92.5% vs 91.1%, P= .8374), but they published fewer total papers by the end of cardiothoracic surgery fellowship (3.0 vs 7.0, P= .0001) and fewer papers per year as an academic attending (0.8 vs 2.9, P < .0001). Nevertheless, the majority of cardiothoracic surgery faculty who started in non-academic practice are currently active in research (68.8%), and 2 such surgeons received National Institutes of Health R01 funding.CONCLUSION: Transitioning from non-academic to academic practice is an uncommon but feasible pathway for interested cardiothoracic surgeons.

    View details for DOI 10.1016/j.surg.2021.06.012

    View details for PubMedID 34294448

  • The Use of Factor Eight Inhibitor Bypass Activity (FEIBA) for the Treatment of Perioperative Hemorrhage in Left Ventricular Assist Device Implantation. Journal of cardiothoracic and vascular anesthesia O'Donnell, C., Rodriguez, A. J., Madhok, J., Sharifi, H., Wang, H., O'Brien, C. G., Boyd, J., Hiesinger, W., Hsu, J., Hill, C. C. 2021


    OBJECTIVE: To test the hypothesis that factor eight inhibitor bypassing activity (FEIBA) can be used to control bleeding following left ventricular assist device (LVAD) implantation without increasing the 14-day composite thrombotic outcome of pump thrombus, ischemic cerebrovascular accidents, pulmonary embolism, and deep venous thrombosis.DESIGN: Retrospective cohort study.SETTING: Academic hospital.PARTICIPANTS: Three hundred nineteen consecutive patients who underwent LVAD implantation (December 1, 2009 to December 30, 2018).INTERVENTION: FEIBA administered to control perioperative hemorrhage.MEASUREMENTS AND MAIN RESULTS: The 82 patients (25.7%) in the FEIBA cohort had more risk factors for perioperative hemorrhage, such as lower preoperative platelet count (169 ± 66 v 194 ± 68 * 103/mL, p = 0.004), prior cardiac surgery (36.6% v 21.9%, p = 0.008), and longer cardiopulmonary bypass (CPB) time (100.3 v 75.2 minutes, p = 0.001) than the 237 controls. After 16.6 units (95% CI: 14.3-18.9) of blood products were given, 992 units (95% CI: 821-1163) of FEIBA were required to control bleeding in the FEIBA cohort. Compared to the controls, there were no differences in the 14-day composite thrombotic outcome (11.0% v 7.6%, p = 0.343) or mortality rate (3.7% v 1.3%, p = 0.179). Multivariate logistical regression identified preoperative international normalized ratio (odds ratio [OR]: 1.30, 95% CI: 1.04-1.62) and CPB time (OR: 1.11, 95% CI: 1.02-1.20) as risk factors for 14-day thrombotic events, but FEIBA usage was not associated with an increased risk.CONCLUSIONS: In this retrospective cohort study, the use of FEIBA (1,000 units, 13 units/kg) to control perioperative hemorrhage following LVAD implantation was not associated with increases in mortality or composite thrombotic outcome.

    View details for DOI 10.1053/j.jvca.2021.04.030

    View details for PubMedID 34034934

  • Career Research Productivity Correlates With Medical School Ranking Among Cardiothoracic Surgeons. The Journal of surgical research Bajaj, S. S., Wang, H., Williams, K. M., Pickering, J. M., Heiler, J. C., Manjunatha, K., Sanchez, M., O'Donnell, C. T., Boyd, J. H. 2021; 264: 99–106


    BACKGROUND: The foundation for a successful academic surgical career begins in medical school. We examined whether attending a top-ranked medical school is correlated with enhanced research productivity and faster career advancement among academic cardiothoracic (CT) surgeons.MATERIALS AND METHODS: Research profiles and professional histories were obtained from publicly available sources for all CT surgery faculty at accredited US CT surgery teaching hospitals in 2018 (n=992). We focused on surgeons who completed medical school in the United States during or after 1990, the first-year US News & World Report released its annual medical school research rankings (n=451). Subanalyses focused on surgeons who completed a research fellowship (n=299) and those who did not (n=152).RESULTS: A total of 124 surgeons (27.5%) attended a US News & World Report top 10 medical school, whereas 327 (72.5%) did not. Surgeons who studied at a top 10 medical school published more articles per year as an attending surgeon (3.2 versus 1.9; P<0.0001), leading to more total publications (51.5 versus 27.0; P<0.0001) and a higher H-index (16.0 versus 11.0; P<0.0001) over a similar career duration (11.0 versus 10.0y; P=0.1294). These differences in career-long research productivity were statistically significant regardless of whether the surgeons completed a research fellowship or not. The surgeons in both groups, however, required a similar number of years to reach associate professor rank (P=0.6993) and full professor rank (P=0.7811) after starting their first attending job.CONCLUSIONS: Attending a top-ranked medical school is associated with enhanced future research productivity but not with faster career advancement in academic CT surgery.

    View details for DOI 10.1016/j.jss.2021.01.008

    View details for PubMedID 33794390

  • Successful beating-heart repair of pulmonary artery dissection using a composite valve-tube graft. Journal of cardiac surgery de Biasi, A. R., Wang, H., Medina, M. G., Burton, E., Ogden, W. D. 2021


    Pulmonary artery dissection is rare but highly lethal. Recent reports suggest that surgical repair of pulmonary artery dissection may yield good outcomes in selected patients, although postoperative right ventricular failure and death have been described. Currently, only one patient over age 60 years old has been reported to survive open surgical repair of pulmonary artery dissection. Here, we present the case of a sexagenarian with pulmonary artery hypertension complicated by a dissected pulmonary artery aneurysm which was successfully repaired using a composite valve-tube graft under a beating-heart strategy.

    View details for DOI 10.1111/jocs.15459

    View details for PubMedID 33651429

  • The Expanding Armamentarium of Innovative Bioengineered Strategies to Augment Cardiovascular Repair and Regeneration Frontiers in Bioengineering and Biotechnology Elde, S., Wang, H., Woo, Y. 2021: 674172


    Cardiovascular disease remains the leading cause of death worldwide. While clinical trials of cell therapy have demonstrated largely neutral results, recent investigations into the mechanisms of natural myocardial regeneration have demonstrated promising new intersections between molecular, cellular, tissue, biomaterial, and biomechanical engineering solutions. New insight into the crucial role of inflammation in natural regenerative processes may explain why previous efforts have yielded only modest degrees of regeneration. Furthermore, the new understanding of the interdependent relationship of inflammation and myocardial regeneration have catalyzed the emergence of promising new areas of investigation at the intersection of many fields.

    View details for DOI 10.3389/fbioe.2021.674172

    View details for PubMedCentralID PMC8205517

  • 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

  • National Institutes of Health R01 Grant Funding Is Associated with Enhanced Research Productivity and Career Advancement Among Academic Cardiothoracic Surgeons. Seminars in thoracic and cardiovascular surgery Bajaj, S. S., Wang, H., Williams, K. M., Pickering, J. M., Heiler, J. C., Manjunatha, K., O'Donnell, C. T., Sanchez, M., Boyd, J. H. 2020


    National Institutes of Health (NIH) funding has declined among cardiothoracic surgeons. R01 grants are a well-known mechanism to support high-impact research, and we sought to clarify the association between NIH funding and academic achievement. We hypothesized that cardiothoracic surgeons who acquired R01 funding exhibit greater research output and faster career advancement. All cardiothoracic surgeons (n=992) working at accredited United States cardiothoracic surgery training hospitals in 2018 were included. Institutional webpages, Scopus, and Grantome were utilized to collect publicly-available data regarding each surgeon's training and career history, research publications, and NIH funding. 78 (7.9%) surgeons obtained R01 funding as a principal investigator, while 914 (92.1%) did not. R01-funded surgeons started their attending careers earlier (1998 vs 2005, p<0.0001) and were more likely to have pursued dedicated research training (p<0.0001). R01-funded surgeons authored 5.3 publications/year before their first R01 grant, 9.3 during the grant period, and 8.6 after the grant expired, all of which were greater than the publication rate of non-R01-funded surgeons at comparable career timepoints (2.0-3.0 publications/year, p<0.0001). Among time-matched surgeons who completed medical school in 1998 or earlier (n=73 R01-funded vs n=602 non-funded), R01-funded surgeons have published more total publications (178.0 vs 56.5 papers, p<0.0001) and exhibit a greater H-index (41.0 vs 19.0, p<0.0001). R01-funded surgeons have also advanced to higher academic ranks (p<0.0001) and are more likely to be chiefs of their departments or divisions (42.5% vs 25.7%, p=0.0035). Cardiothoracic surgeons who obtain R01 funding exhibit greater research productivity and faster career advancement.

    View details for DOI 10.1053/j.semtcvs.2020.12.002

    View details for PubMedID 33359763

  • New Attending Surgeons Hired by Their Training Institution Exhibit Greater Research Productivity. The Annals of thoracic surgery Bajaj, S. S., Wang, H., Williams, K. M., Pickering, J. M., Heiler, J. C., Manjunatha, K., O'Donnell, C. T., Sanchez, M., Boyd, J. H. 2020


    BACKGROUND: A first attending job often sets the tone for academic surgeons' future careers, and many graduating trainees are faced with the decision to begin their career at their training institution or another institution. We hypothesized that surgeons hired as first-time faculty at their cardiothoracic surgery fellowship (CSF) institution exhibit greater research productivity and career advancement than those hired as first-time faculty at a different institution.METHODS: Cardiothoracic surgeons who were listed as clinical faculty at all 77 accredited U.S. cardiothoracic surgery training programs and who trained via the general surgery residency and CSF pathway in 2018 were included (n=904). Surgeon-specific data regarding professional history, publications, and grant funding were obtained from publicly available sources.RESULTS: 294/904 (32.5%) surgeons were hired as first-time faculty at their CSF institution while 610/904 (67.5%) surgeons were hired at a different institution (start year 2005 vs 2006, p=0.3424). Both groups exhibited similar research productivity upon starting their first job (total papers: 7.0 vs 7.0, p=0.5913). Following them to the present, surgeons hired at their CSF institution produced more total papers (64.5 vs 39.0, p<0.0001) and exhibited a higher H-index (20.0 vs 14.0, p<0.0001). Surgeons in both groups required a similar amount of time to achieve associate (p=0.2079) and full professor (p=0.5925) ranks.CONCLUSIONS: Surgeons hired as first-time faculty at their CSF institution may experience benefits to research productivity but not career advancement. Trainees may find it advantageous to begin their careers in a familiar environment where they have already formed a robust specialty-specific network.

    View details for DOI 10.1016/j.athoracsur.2020.09.026

    View details for PubMedID 33152331

  • Impact of advanced clinical fellowship training on future research productivity and career advancement in adult cardiac surgery. Surgery Wang, H., Bajaj, S. S., Williams, K. M., Pickering, J. M., Heiler, J. C., Manjunatha, K., O'Donnell, C. T., Sanchez, M., Boyd, J. H. 2020


    BACKGROUND: Advanced clinical fellowships are important for training surgeons with a niche expertise. Whether this additional training impacts future academic achievement, however, remains unknown. Here, we investigated the impact of advanced fellowship training on research productivity and career advancement among active, academic cardiac surgeons. We hypothesized that advanced fellowships do not significantly boost future academic achievement.METHODS: Using online sources (eg, department webpages, CTSNet, Scopus, Grantome), we studied adult cardiac surgeons who are current faculty at accredited United States cardiothoracic surgery training programs, and who have practiced only at United States academic centers since 1986 (n= 227). Publicly available data regarding career advancement, research productivity, and grant funding were collected. Data are expressed as counts or medians.RESULTS: In our study, 78 (34.4%) surgeons completed an advanced clinical fellowship, and 149 (65.6%) did not. Surgeons who pursued an advanced fellowship spent more time focused on surgical training (P < .0001), and those who did not were more likely to have completed a dedicated research fellowship (P= .0482). Both groups exhibited similar cumulative total publications (P= .6862), H-index (P= .6232), frequency of National Institutes of Health grant funding (P= .8708), and time to achieve full professor rank (P= .7099). After stratification by current academic rank, or by whether surgeons pursued a dedicated research fellowship, completion of an advanced clinical fellowship was not associated with increased research productivity or accelerated career advancement.CONCLUSION: Academic adult cardiac surgeons who pursue advanced clinical fellowships exhibit similar research productivity and similar career advancement as those who do not pursue additional clinical training.

    View details for DOI 10.1016/j.surg.2020.06.016

    View details for PubMedID 32747139

  • 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

  • Transcriptional Profiling of Normal, Stenotic, and Regurgitant Human Aortic Valves. Genes Greene, C. L., Jaatinen, K. J., Wang, H., Koyano, T. K., Bilbao, M. S., Woo, Y. J. 2020; 11 (7)


    The genetic mechanisms underlying aortic stenosis (AS) and aortic insufficiency (AI) disease progression remain unclear. We hypothesized that normal aortic valves and those with AS or AI all exhibit unique transcriptional profiles. Normal control (NC) aortic valves were collected from non-matched donor hearts that were otherwise acceptable for transplantation (n = 5). Valves with AS or AI (n = 5, each) were collected from patients undergoing surgical aortic valve replacement. High-throughput sequencing of total RNA revealed 6438 differentially expressed genes (DEGs) for AS vs. NC, 4994 DEGs for AI vs. NC, and 2771 DEGs for AS vs. AI. Among 21 DEGs of interest, APCDD1L, CDH6, COL10A1, HBB, IBSP, KRT14, PLEKHS1, PRSS35, and TDO2 were upregulated in both AS and AI compared to NC, whereas ALDH1L1, EPHB1, GPX3, HIF3A, and KCNT1 were downregulated in both AS and AI (p < 0.05). COL11A1, H19, HIF1A, KCNJ6, PRND, and SPP1 were upregulated only in AS, and NPY was downregulated only in AS (p < 0.05). The functional network for AS clustered around ion regulation, immune regulation, and lipid homeostasis, and that for AI clustered around ERK1/2 regulation. Overall, we report transcriptional profiling data for normal human aortic valves from non-matched donor hearts that were acceptable for transplantation and demonstrated that valves with AS and AI possess unique genetic signatures. These data create a roadmap for the development of novel therapeutics to treat AS and AI.

    View details for DOI 10.3390/genes11070789

    View details for PubMedID 32674273

  • 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

  • Safety of photosynthetic Synechococcus elongatus for in vivo cyanobacteria-mammalian symbiotic therapeutics. Microbial biotechnology Williams, K. M., Wang, H., Paulsen, M. J., Thakore, A. D., Rieck, M., Lucian, H. J., Grady, F., Hironaka, C. E., Chien, A. J., Farry, J. M., Shin, H. S., Jaatinen, K. J., Eskandari, A., Stapleton, L. M., Steele, A. N., Cohen, J. E., Woo, Y. J. 2020


    The cyanobacterium Synechococcus elongatus (SE) has been shown to rescue ischaemic heart muscle after myocardial infarction by photosynthetic oxygen production. Here, we investigated SE toxicity and hypothesized that systemic SE exposure does not elicit a significant immune response in rats. Wistar rats intravenously received SE (n=12), sterile saline (n=12) or E. coli lipopolysaccharide (LPS, n=4), and a subset (8 SE, 8 saline) received a repeat injection 4weeks later. At baseline, 4h, 24h, 48h, 8days and 4weeks after injection, clinical assessments, blood cultures, blood counts, lymphocyte phenotypes, liver function tests, proinflammatory cytokines and immunoglobulins were assessed. Across all metrics, SE rats responded comparably to saline controls, displaying no clinically significant immune response. As expected, LPS rats exhibited severe immunological responses. Systemic SE administration does not induce sepsis or toxicity in rats, thereby supporting the safety of cyanobacteria-mammalian symbiotic therapeutics using this organism.

    View details for DOI 10.1111/1751-7915.13596

    View details for PubMedID 32476224

  • 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

  • A novel 3D-Printed preferential posterior mitral annular dilation device delineates regurgitation onset threshold in an ex vivo heart simulator. Medical engineering & physics Imbrie-Moore, A. M., Paullin, C. C., Paulsen, M. J., Grady, F., Wang, H., Hironaka, C. E., Farry, J. M., Lucian, H. J., Woo, Y. J. 2020


    Mitral regurgitation (MR) due to annular dilation occurs in a variety of mitral valve diseases and is observed in many patients with heart failure due to mitral regurgitation. To understand the biomechanics of MR and ultimately design an optimized annuloplasty ring, a representative disease model with asymmetric dilation of the mitral annulus is needed. This work shows the design and implementation of a 3D-printed valve dilation device to preferentially dilate the posterior mitral valve annulus. Porcine mitral valves (n=3) were sewn into the device and mounted within a left heart simulator that generates physiologic pressures and flows through the valves, while chordal forces were measured. The valves were incrementally dilated, inducing MR, while hemodynamic and force data were collected. Flow analysis demonstrated that MR increased linearly with respect to percent annular dilation when dilation was greater than a 25.6% dilation threshold (p<0.01). Pre-threshold, dilation did not cause significant increases in regurgitant fraction. Forces on the chordae tendineae increased as dilation increased prior to the identified threshold (p < 0.01); post-threshold, the MR resulted in highly variable forces. Ultimately, this novel dilation device can be used to more accurately model a wide range of MR disease states and their corresponding repair techniques using ex vivo experimentation. In particular, this annular dilation device provides the means to investigate the design and optimization of novel annuloplasty rings.

    View details for DOI 10.1016/j.medengphy.2020.01.005

    View details for PubMedID 32008935

  • 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

  • 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

  • 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

  • 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

  • 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

  • Multi-phase catheter-injectable hydrogel enables dual-stage protein-engineered cytokine release to mitigate adverse left ventricular remodeling following myocardial infarction in a small animal model and a large animal model. Cytokine Steele, A. N., Paulsen, M. J., Wang, H. n., Stapleton, L. M., Lucian, H. J., Eskandari, A. n., Hironaka, C. E., Farry, J. M., Baker, S. W., Thakore, A. D., Jaatinen, K. J., Tada, Y. n., Hollander, M. J., Williams, K. M., Seymour, A. J., Totherow, K. P., Yu, A. C., Cochran, J. R., Appel, E. A., Woo, Y. J. 2020; 127: 154974


    Although ischemic heart disease is the leading cause of death worldwide, mainstay treatments ultimately fail because they do not adequately address disease pathophysiology. Restoring the microvascular perfusion deficit remains a significant unmet need and may be addressed via delivery of pro-angiogenic cytokines. The therapeutic effect of cytokines can be enhanced by encapsulation within hydrogels, but current hydrogels do not offer sufficient clinical translatability due to unfavorable viscoelastic mechanical behavior which directly impacts the ability for minimally-invasive catheter delivery. In this report, we examine the therapeutic implications of dual-stage cytokine release from a novel, highly shear-thinning biocompatible catheter-deliverable hydrogel. We chose to encapsulate two protein-engineered cytokines, namely dimeric fragment of hepatocyte growth factor (HGFdf) and engineered stromal cell-derived factor 1α (ESA), which target distinct disease pathways. The controlled release of HGFdf and ESA from separate phases of the hyaluronic acid-based hydrogel allows extended and pronounced beneficial effects due to the precise timing of release. We evaluated the therapeutic efficacy of this treatment strategy in a small animal model of myocardial ischemia and observed a significant benefit in biological and functional parameters. Given the encouraging results from the small animal experiment, we translated this treatment to a large animal preclinical model and observed a reduction in scar size, indicating this strategy could serve as a potential adjunct therapy for the millions of people suffering from ischemic heart disease.

    View details for DOI 10.1016/j.cyto.2019.154974

    View details for PubMedID 31978642

  • Long-term outcome of orthotopic heart transplantation in Asians: An analysis of the United Network of Organ Sharing database. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Kohsaka, S. n., Shudo, Y. n., Wang, H. n., Lingala, B. n., Kawana, M. n., Woo, Y. J. 2020

    View details for DOI 10.1016/j.healun.2020.07.016

    View details for PubMedID 32948416

  • A Bioengineered Neuregulin-Hydrogel Therapy Reduces Scar Size and Enhances Post-Infarct Ventricular Contractility in an Ovine Large Animal Model. Journal of cardiovascular development and disease Cohen, J. E., Goldstone, A. B., Wang, H. n., Purcell, B. P., Shudo, Y. n., MacArthur, J. W., Steele, A. N., Paulsen, M. J., Edwards, B. B., Aribeana, C. N., Cheung, N. C., Burdick, J. A., Woo, Y. J. 2020; 7 (4)


    The clinical efficacy of neuregulin (NRG) in the treatment of heart failure is hindered by off-target exposure due to systemic delivery. We previously encapsulated neuregulin in a hydrogel (HG) for targeted and sustained myocardial delivery, demonstrating significant induction of cardiomyocyte proliferation and preservation of post-infarct cardiac function in a murine myocardial infarction (MI) model. Here, we performed a focused evaluation of our hydrogel-encapsulated neuregulin (NRG-HG) therapy's potential to enhance cardiac function in an ovine large animal MI model. Adult male Dorset sheep (n = 21) underwent surgical induction of MI by coronary artery ligation. The sheep were randomized to receive an intramyocardial injection of saline, HG only, NRG only, or NRG-HG circumferentially around the infarct borderzone. Eight weeks after MI, closed-chest intracardiac pressure-volume hemodynamics were assessed, followed by heart explant for infarct size analysis. Compared to each of the control groups, NRG-HG significantly augmented left ventricular ejection fraction (p = 0.006) and contractility based on the slope of the end-systolic pressure-volume relationship (p = 0.006). NRG-HG also significantly reduced infarct scar size (p = 0.002). Overall, using a bioengineered hydrogel delivery system, a one-time dose of NRG delivered intramyocardially to the infarct borderzone at the time of MI in adult sheep significantly reduces scar size and enhances ventricular contractility at 8 weeks after MI.

    View details for DOI 10.3390/jcdd7040053

    View details for PubMedID 33212844

  • Women in Thoracic Surgery Scholarship: Impact on Career Path and Interest in Cardiothoracic Surgery. The Annals of thoracic surgery Williams, K. M., Hironaka, C. E., Wang, H. n., Bajaj, S. S., O'Donnell, C. T., Sanchez, M. n., Boyd, J. n., Kane, L. n., Backhus, L. n. 2020


    Women remain underrepresented in Cardiothoracic Surgery (CTS). In 2005, Women in Thoracic Surgery (WTS) began offering scholarships to promote engagement of women in CTS careers. This study explores the effect of WTS scholarships on CTS career milestones.We assessed career development using the number of awardees matching into CTS residency/fellowship, American Board of Thoracic Surgery (ABTS) certification, and academic CTS appointment. Scholarship awardee data were obtained from our WTS database. Comparison data were gathered from the National Residency Match Program and ABTS. Details of the current roles of ABTS certified women were determined from public resources. Qualitative results were gathered from post-scholarship surveys.106 WTS scholarships have been awarded to 38 medical students (MS, 36%), 41 General Surgery residents (GR, 39%), and 27 CTS residents/fellows (CR, 25%). Among MS, 26% of awardees entered integrated CTS residency (vs. <0.1% for medical students, p<0.0001), while 37% entered general surgery residency (vs. 4.8% for medical students, p<0.0001). Of GR awardees, 59% entered CTS fellowships (vs. 7.7% for general surgery residents, p<0.0001), and of CR awardees, 100% earned ABTS certification (vs. 73% ABTS pass rate, p=.01). Of ABTS certified awardees, 44% are practicing CT surgeons at U.S. academic training institutions (vs. 33% of non-awardee ABTS certified women, p=0.419). All awardees reported that their scholarship was valuable in their development.Receipt of a WTS scholarship is associated with successful pursuit of CTS career milestones at significantly higher rates than contemporaries. These scholarships foster a supportive community for women trainees in CTS.

    View details for DOI 10.1016/j.athoracsur.2020.07.020

    View details for PubMedID 32961134

  • Mitral chordae tendineae force profile characterization using a posterior ventricular anchoring neochordal repair model for mitral regurgitation in a three-dimensional-printed ex vivo left heart simulator. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Paulsen, M. J., Imbrie-Moore, A. M., Wang, H., Bae, J. H., Hironaka, C. E., Farry, J. M., Lucian, H. J., Thakore, A. D., MacArthur, J. W., Cutkosky, M. R., Woo, Y. J. 2019


    OBJECTIVES: Posterior ventricular anchoring neochordal (PVAN) repair is a non-resectional technique for correcting mitral regurgitation (MR) due to posterior leaflet prolapse, utilizing a single suture anchored in the myocardium behind the leaflet. This technique has demonstrated clinical efficacy, although a theoretical limitation is stability of the anchoring suture. We hypothesize that the PVAN suture positions the leaflet for coaptation, after which forces are distributed evenly with low repair suture forces.METHODS: Porcine mitral valves were mounted in a 3-dimensional-printed heart simulator and chordal forces, haemodynamics and echocardiography were collected at baseline, after inducing MR by severing chordae, and after PVAN repair. Repair suture forces were measured with a force-sensing post positioned to mimic in vivo suture placement. Forces required to pull the myocardial suture free were also determined.RESULTS: Relative primary and secondary chordae forces on both leaflets were elevated during prolapse (P<0.05). PVAN repair eliminated MR in all valves and normalized chordae forces to baseline levels on anterior primary (0.37±0.23 to 0.22±0.09 N, P<0.05), posterior primary (0.62±0.37 to 0.14±0.05 N, P=0.001), anterior secondary (1.48±0.52 to 0.85±0.43 N, P<0.001) and posterior secondary chordae (1.42±0.69 to 0.59±0.17 N, P=0.005). Repair suture forces were minimal, even compared to normal primary chordae forces (0.08±0.04 vs 0.19±0.08 N, P=0.002), and were 90 times smaller than maximum forces tolerated by the myocardium (0.08±0.04 vs 6.9±1.3 N, P<0.001).DISCUSSION: PVAN repair eliminates MR by positioning the posterior leaflet for coaptation, distributing forces throughout the valve. Given extremely low measured forces, the strength of the repair suture and the myocardium is not a limitation.

    View details for DOI 10.1093/ejcts/ezz258

    View details for PubMedID 31638697

  • Heart-lung transplantation with concomitant aortic arch reconstruction for Eisenmenger syndrome and type B interrupted aortic arch. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Wang, H., Shudo, Y., MacArthur, J. W., Woo, Y. J. 2019

    View details for DOI 10.1016/j.healun.2019.09.002

    View details for PubMedID 31570290

  • Vascularization of Engineered Spatially Patterned Myocardial Tissue Derived From Human Pluripotent Stem Cells in vivo. Frontiers in bioengineering and biotechnology Wanjare, M., Kawamura, M., Hu, C., Alcazar, C., Wang, H., Woo, Y. J., Huang, N. F. 2019; 7: 208


    Tissue engineering approaches to regenerate myocardial tissue after disease or injury is promising. Integration with the host vasculature is critical to the survival and therapeutic efficacy of engineered myocardial tissues. To create more physiologically oriented engineered myocardial tissue with organized cellular arrangements and endothelial interactions, randomly oriented or parallel-aligned microfibrous polycaprolactone scaffolds were seeded with human pluripotent stem cell-derived cardiomyocytes (iCMs) and/or endothelial cells (iECs). The resultant engineered myocardial tissues were assessed in a subcutaneous transplantation model and in a myocardial injury model to evaluate the effect of scaffold anisotropy and endothelial interactions on vascular integration of the engineered myocardial tissue. Here we demonstrated that engineered myocardial tissue composed of randomly oriented scaffolds seeded with iECs promoted the survival of iECs for up to 14 days. However, engineered myocardial tissue composed of aligned scaffolds preferentially guided the organization of host capillaries along the direction of the microfibers. In a myocardial injury model, epicardially transplanted engineered myocardial tissues composed of randomly oriented scaffolds seeded with iCMs augmented microvessel formation leading to a significantly higher arteriole density after 4 weeks, compared to engineered tissues derived from aligned scaffolds. These findings that the scaffold microtopography imparts differential effect on revascularization, in which randomly oriented scaffolds promote pro-survival and pro-angiogenic effects, and aligned scaffolds direct the formation of anisotropic vessels. These findings suggest a dominant role of scaffold topography over endothelial co-culture in modulating cellular survival, vascularization, and microvessel architecture.

    View details for DOI 10.3389/fbioe.2019.00208

    View details for PubMedID 31552234

    View details for PubMedCentralID PMC6733921

  • Custom Patient-Specific Three-Dimensional Printed Mitral Valve Models for Pre-Operative Patient Education Enhance Patient Satisfaction and Understanding JOURNAL OF MEDICAL DEVICES-TRANSACTIONS OF THE ASME Hung, K. S., Paulsen, M. J., Wang, H., Hironaka, C., Woo, Y. 2019; 13 (3)

    View details for DOI 10.1115/1.4043737

    View details for Web of Science ID 000483046800013

  • Modeling conduit choice for valve-sparing aortic root replacement on biomechanics with a 3-dimensional-printed heart simulator JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Paulsen, M. J., Kasinpila, P., Imbrie-Moore, A. M., Wang, H., Hironaka, C. E., Koyano, T. K., Fong, R., Chiu, P., Goldstone, A. B., Steele, A. N., Stapleton, L. M., Ma, M., Woo, Y. 2019; 158 (2): 392–403
  • Ex vivo biomechanical study of apical versus papillary neochord anchoring for mitral regurgitation. The Annals of thoracic surgery Imbrie-Moore, A. M., Paulsen, M. J., Thakore, A. D., Wang, H., Hironaka, C. E., Lucian, H. J., Farry, J. M., Edwards, B. B., Bae, J. H., Cutkosky, M. R., Woo, Y. J. 2019


    BACKGROUND: Neochordoplasty is an important repair technique, though optimal anchoring position is unknown. While typically anchored at papillary muscles, new percutaneous devices anchor the chordae at or near the ventricular apex, which may have an effect on chordal forces and the long-term durability of the repair.METHODS: Porcine mitral valves (n=6) were mounted in a left heart simulator that generates physiological pressure and flow through the valves while chordal forces were measured using Fiber Bragg Grating strain gauge sensors. Isolated mitral regurgitation was induced by cutting P2 primary chordae and the regurgitant valve was repaired using PTFE neochord with apical anchoring, followed by papillary muscle fixation for comparison. In both cases, the neochord was anchored to a customized force-sensing post positioned to mimic the relevant in vivo placement.RESULTS: Echocardiographic and hemodynamic data confirmed that the repairs restored physiologic hemodynamics. Forces on the chordae and neochord were lower for papillary fixation than the apical (p=0.003). Additionally, the maximum rate of change of force was higher for the chordae and neochord for apical fixation when compared to papillary (p=0.028).CONCLUSIONS: Apical point of anchoring results in higher forces on the chordae and neochord stitch as well as an increased rate of loading on the neochord when compared to the papillary muscle fixation. These results suggest the papillary fixation repair may have superior durability.

    View details for PubMedID 30836099

  • A Biocompatible Therapeutic Catheter-Deliverable Hydrogel for In Situ Tissue Engineering. Advanced healthcare materials Steele, A. N., Stapleton, L. M., Farry, J. M., Lucian, H. J., Paulsen, M. J., Eskandari, A., Hironaka, C. E., Thakore, A. D., Wang, H., Yu, A. C., Chan, D., Appel, E. A., Woo, Y. J. 2019: e1801147


    Hydrogels have emerged as a diverse class of biomaterials offering a broad range of biomedical applications. Specifically, injectable hydrogels are advantageous for minimally invasive delivery of various therapeutics and have great potential to treat a number of diseases. However, most current injectable hydrogels are limited by difficult and time-consuming fabrication techniques and are unable to be delivered through long, narrow catheters, preventing extensive clinical translation. Here, the development of an easily-scaled, catheter-injectable hydrogel utilizing a polymer-nanoparticle crosslinking mechanism is reported, which exhibits notable shear-thinning and self-healing behavior. Gelation of the hydrogel occurs immediately upon mixing the biochemically modified hyaluronic acid polymer with biodegradable nanoparticles and can be easily injected through a high-gauge syringe due to the dynamic nature of the strong, yet reversible crosslinks. Furthermore, the ability to deliver this novel hydrogel through a long, narrow, physiologically-relevant catheter affixed with a 28-G needle is highlighted, with hydrogel mechanics unchanged after delivery. Due to the composition of the gel, it is demonstrated that therapeutics can be differentially released with distinct elution profiles, allowing precise control over drug delivery. Finally, the cell-signaling and biocompatibility properties of this innovative hydrogel are demonstrated, revealing its wide range of therapeutic applications.

    View details for PubMedID 30714355

  • Cardioaortic replacement for a ruptured root pseudoaneurysm with pulsatile subcutaneous extension. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Wang, H., Shudo, Y., Hittinger, S. A., Woo, Y. J. 2019


    Orthotopic heart transplantation with concomitant aortic surgery is rarely performed. Herein, we describe the successful management of a patient with an otherwise inoperable, ruptured aortic root pseudoaneurysm using combined cardioaortic replacement under hypothermic circulatory arrest.

    View details for PubMedID 30608529

  • Development and ex vivo validation of novel force-sensing neochordae for measuring chordae tendineae tension in the mitral valve apparatus using optical fibers with embedded Bragg gratings. Journal of biomechanical engineering Paulsen, M. J., Bae, J. H., Imbrie-Moore, A. n., Wang, H. n., Hironaka, C. n., Farry, J. M., Lucian, H. n., Thakore, A. n., Cutkosky, M. R., Woo, Y. J. 2019


    Few technologies exist that can provide quantitative data on forces within the mitral valve apparatus. Marker-based strain measurements can be performed, but chordal geometry and restricted optical access are limitations. Foil-based strain sensors have been described and work well, but the sensor footprint limits the number of chordae that can be measured. We instead utilized Fiber Bragg Grating (FBG) sensors-optical strain gauges made of 125µm diameter silica fibers- to overcome some limitations of previous methods of measuring chordae tendineae forces. Using FBG sensors, we created a force-sensing neochord that mimics the natural shape and movement of native chordae. FBG sensors reflect a specific wavelength of light depending on the spatial period of gratings. When force is applied, the gratings move relative to one another, shifting the wavelength of reflected light. This shift is directly proportional to force applied. The FBG sensors were housed in a protective sheath fashioned from a 0.025" flat coil, and attached to the chordae using polytetrafluoroethylene suture. The function of the force-sensing neochordae was validated in a 3D-printed left heart simulator, which demonstrated that FBG sensors provide highly sensitive force measurements of mitral valve chordae at a temporal resolution of 1000 Hz. As ventricular pressures increased, such as in hypertension, chordae forces also increased. Overall, FBG sensors are a viable, durable, and high-fidelity sensing technology that can be effectively used to measure mitral valve chordae forces and overcome some limitations of other such technologies.

    View details for DOI 10.1115/1.4044142

    View details for PubMedID 31253992

  • Evaluation of Risk Factors for Heart-Lung Transplant Recipient Outcome: An Analysis of the United Network for Organ Sharing Database. Circulation Shudo, Y. n., Wang, H. n., Lingala, B. n., He, H. n., Kim, F. Y., Hiesinger, W. n., Lee, A. M., Boyd, J. H., Currie, M. n., Woo, Y. J. 2019; 140 (15): 1261–72


    Heart-lung transplantation (HLTx) is an effective treatment for patients with advanced cardiopulmonary failure. However, no large multicenter study has focused on the relationship between donor and recipient risk factors and post-HLTx outcomes. Thus, we investigated this issue using data from the United Network for Organ Sharing database.All adult patients (age ≥18 years) registered in the United Network for Organ Sharing database who underwent HLTx between 1987 and 2017 were included (n=997). We stratified the cohort by patients who were alive without retransplant at 1 year (n=664) and patients who died or underwent retransplant within 1 year of HLTx (n=333). The primary outcome was the influence of donor and recipient characteristics on 1-year post-HLTx recipient death or retransplant. Kaplan-Meier curves were created to assess overall freedom from death or retransplant. To obtain a better effect estimation on hazard and survival time, the parametric Accelerated Failure Time model was chosen to perform time-to-event modeling analyses.Overall graft survival at 1-year post-HLTx was 66.6%. Of donors, 53% were male, and the mean age was 28.2 years. Univariable analysis showed advanced donor age, recipient male sex, recipient creatinine, recipient history of prior cardiac or lung surgery, recipient extracorporeal membrane oxygenation support, transplant year, and transplant center volume were associated with 1-year post-HLTx death or retransplant. On multivariable analysis, advanced donor age (hazard ratio [HR], 1.017; P=0.0007), recipient male sex (HR, 1.701; P=0.0002), recipient extracorporeal membrane oxygenation support (HR, 4.854; P<0.0001), transplant year (HR, 0.962; P<0.0001), and transplantation at low-volume (HR, 1.694) and medium-volume centers (HR, 1.455) in comparison with high-volume centers (P=0.0007) remained as significant predictors of death or retransplant. These predictors were incorporated into an equation capable of estimating the preliminary probability of graft survival at 1-year post-HLTx on the basis of preoperative factors alone.HLTx outcomes may be improved by considering the strong influence of donor age, recipient sex, recipient hemodynamic status, and transplant center volume. Marginal donors and recipients without significant factors contributing to poor post-HLTx outcomes may still be considered for transplantation, potentially with less impact on the risk of early postoperative death or retransplant.

    View details for DOI 10.1161/CIRCULATIONAHA.119.040682

    View details for PubMedID 31589491

  • Utilization of Del Nido Cardioplegia in Adult Coronary Artery Bypass Grafting - A Retrospective Analysis. Circulation journal : official journal of the Japanese Circulation Society O'Donnell, C., Wang, H., Tran, P., Miller, S., Shuttleworth, P., Boyd, J. H. 2018


    BACKGROUND: Studies assessing the safety and effectiveness of Del Nido cardioplegia for adult cardiac surgery remain limited. We investigated early outcomes after coronary artery bypass grafting (CABG) using single-dose Del Nido cardioplegia vs. conventional multi-dose blood cardioplegia. Methods and Results: The 81 consecutive patients underwent isolated CABG performed by a single surgeon. The initial 27 patients received anterograde blood cardioplegia, while the subsequent 54 patients received anterograde Del Nido cardioplegia. There were no differences in the baseline characteristics of each group nor any differences in the 30-day incidences of myocardial infarction, all-cause death, and readmission following surgery. The use of Del Nido cardioplegia was associated with shorter cardiopulmonary bypass time (98 vs. 115 min, P=0.011), shorter cross-clamp time (74 vs. 87 min, P=0.006), and decreased need for intraoperative defibrillation (13.0% vs. 33.3%, P=0.030) compared with blood cardioplegia. To control for the difference in cross-clamp time, we performed propensity score matching with a logistical treatment model and confirmed that Del Nido cardioplegia provided similar outcomes as blood cardioplegia and also reduced the need for defibrillation independent of cross-clamp time.CONCLUSIONS: Compared with conventional blood cardioplegia, Del Nido cardioplegia provided excellent myocardial protection with reduced need for intraoperative defibrillation, shorter bypass and cross-clamp times, and comparable early clinical outcomes for adult patients undergoing CABG.

    View details for PubMedID 30531128

  • Rapid Self-Assembly of Bioengineered Cardiovascular Bypass Grafts From Scaffold-Stabilized, Tubular Bilevel Cell Sheets. Circulation von Bornstädt, D., Wang, H., Paulsen, M. J., Goldstone, A. B., Eskandari, A., Thakore, A., Stapleton, L., Steele, A. N., Truong, V. N., Jaatinen, K., Hironaka, C., Woo, Y. J. 2018; 138 (19): 2130-2144


    Cardiovascular bypass grafting is an essential treatment for complex cases of atherosclerotic disease. Because the availability of autologous arterial and venous conduits is patient-limited, self-assembled cell-only grafts have been developed to serve as functional conduits with off-the-shelf availability. The unacceptably long production time required to generate these conduits, however, currently limits their clinical utility. Here, we introduce a novel technique to significantly accelerate the production process of self-assembled engineered vascular conduits.Human aortic smooth muscle cells and skin fibroblasts were used to construct bilevel cell sheets. Cell sheets were wrapped around a 22.5-gauge Angiocath needle to form tubular vessel constructs. A thin, flexible membrane of clinically approved biodegradable tissue glue (Dermabond Advanced) served as a temporary, external scaffold, allowing immediate perfusion and endothelialization of the vessel construct in a bioreactor. Subsequently, the matured vascular conduits were used as femoral artery interposition grafts in rats (n=20). Burst pressure, vasoreactivity, flow dynamics, perfusion, graft patency, and histological structure were assessed.Compared with engineered vascular conduits formed without external stabilization, glue membrane-stabilized conduits reached maturity in the bioreactor in one-fifth the time. After only 2 weeks of perfusion, the matured conduits exhibited flow dynamics similar to that of control arteries, as well as physiological responses to vasoconstricting and vasodilating drugs. The matured conduits had burst pressures exceeding 500 mm Hg and had sufficient mechanical stability for surgical anastomoses. The patency rate of implanted conduits at 8 weeks was 100%, with flow rate and hind-limb perfusion similar to those of sham controls. Grafts explanted after 8 weeks showed a histological structure resembling that of typical arteries, including intima, media, adventitia, and internal and external elastic membrane layers.Our technique reduces the production time of self-assembled, cell sheet-derived engineered vascular conduits to 2 weeks, thereby permitting their use as bypass grafts within the clinical time window for elective cardiovascular surgery. Furthermore, our method uses only clinically approved materials and can be adapted to various cell sources, simplifying the path toward future clinical translation.

    View details for DOI 10.1161/CIRCULATIONAHA.118.035231

    View details for PubMedID 30474423

    View details for PubMedCentralID PMC6261325

  • How to start a successful robotic mitral surgery program: It's not just about the surgery! JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Wang, H., Boyd, J. H. 2018; 155 (4): 1472–73

    View details for PubMedID 29317089

  • Heart transplant after profoundly extended ambulatory central venoarterial extracorporeal membrane oxygenation. The Journal of thoracic and cardiovascular surgery Shudo, Y., Wang, H., Ha, R. V., Hayes, A. D., Woo, Y. J. 2018

    View details for PubMedID 29576264

  • Second Arterial Versus Venous Conduits for Multivessel Coronary Artery Bypass Surgery in California. Circulation Goldstone, A. B., Chiu, P. n., Baiocchi, M. n., Wang, H. n., Lingala, B. n., Boyd, J. H., Woo, Y. J. 2018; 137 (16): 1698–1707


    Whether a second arterial conduit improves outcomes after multivessel coronary artery bypass grafting remains unclear. Consequently, arterial conduits other than the left internal thoracic artery are seldom used in the United States.Using a state-maintained clinical registry including all 126 nonfederal hospitals in California, we compared all-cause mortality and rates of stroke, myocardial infarction, repeat revascularization, and sternal wound infection between propensity score-matched cohorts who underwent primary, isolated multivessel coronary artery bypass grafting with the left internal thoracic artery, and who received a second arterial conduit (right internal thoracic artery or radial artery, n=5866) or a venous conduit (n=53 566) between 2006 and 2011. Propensity score matching using 34 preoperative characteristics yielded 5813 matched sets. A subgroup analysis compared outcomes between propensity score-matched recipients of a right internal thoracic artery (n=1576) or a radial artery (n=4290).Second arterial conduit use decreased from 10.7% in 2006 to 9.1% in 2011 (P<0.0001). However, receipt of a second arterial conduit was associated with significantly lower mortality (13.1% versus 10.6% at 7 years; hazard ratio, 0.79; 95% confidence interval [CI], 0.72-0.87), and lower risks of myocardial infarction (hazard ratio, 0.78; 95% CI, 0.70-0.87) and repeat revascularization (hazard ratio, 0.82; 95% CI, 0.76-0.88). In comparison with radial artery grafts, right internal thoracic artery grafts were associated with similar mortality rates (right internal thoracic artery 10.3% versus radial artery 10.7% at 7 years; hazard ratio, 1.10; 95% CI, 0.89-1.37) and individual risks of cardiovascular events, but the risk of sternal wound infection was increased (risk difference, 1.07%; 95% CI, 0.15-2.07).Second arterial conduit use in California is low and declining, but arterial grafts were associated with significantly lower mortality and fewer cardiovascular events. A right internal thoracic artery graft offered no benefit over that of a radial artery, but did increase risk of sternal wound infection. These findings suggest surgeons should consider lowering their threshold for using arterial grafts, and the radial artery may be the preferred second conduit.

    View details for PubMedID 29242351

  • Sodium tanshinone IIA sulfate adjunct therapy reduces high-sensitivity C-reactive protein level in coronary artery disease patients: a randomized controlled trial. Scientific reports Li, S., Jiao, Y., Wang, H., Shang, Q., Lu, F., Huang, L., Liu, J., Xu, H., Chen, K. 2017; 7 (1): 17451


    High-sensitivity C-reactive protein (hs-CRP) is independently associated with cardiovascular events in coronary artery disease (CAD) patients and reducing the hs-CRP level may further benefit this population. We conduct this parallel design, randomized-controlled trial to assess the effectiveness of adjunct sodium tanshinone IIA sulfate (STS) therapy on circulating inflammation markers in CAD patients. Unstable angina or non-ST-elevation myocardial infarction patients with increased hs-CRP level were randomly assigned to atorvastatin-based standard medical therapy or standard therapy plus STS injection (80 mg, once daily for 14 consecutive days). The primary outcome was hs-CRP level. After the 14-day treatment, the experimental group (n = 35) exhibited significantly lower levels of hs-CRP than the control group (n = 35) (1.72 vs 3.20 mg/L, p = 0.0191). Lower levels of interleukin-6, monocyte chemotactic protein-1 (MCP-1), and soluble CD40 ligand were also observed in the experimental group. Angina symptoms were also better controlled in the experimental group. At 30 days after treatment completion, MCP-1 levels remained lower in the experimental group than in the control group (313.88 vs 337.91 pg/mL, p = 0.0078). No serious adverse events occurred. Our study demonstrates that on the basis of standard medical therapy, STS further reduce elevated hs-CRP and other circulating inflammation markers in CAD patients. ( number: ChiCTR-TRC-12002361).

    View details for DOI 10.1038/s41598-017-16980-4

    View details for PubMedID 29234038

    View details for PubMedCentralID PMC5727111

  • Tissue-engineered smooth muscle cell and endothelial progenitor cell bi-level cell sheets prevent progression of cardiac dysfunction, microvascular dysfunction, and interstitial fibrosis in a rodent model of type 1 diabetes-induced cardiomyopathy. Cardiovascular diabetology Kawamura, M. n., Paulsen, M. J., Goldstone, A. B., Shudo, Y. n., Wang, H. n., Steele, A. N., Stapleton, L. M., Edwards, B. B., Eskandari, A. n., Truong, V. N., Jaatinen, K. J., Ingason, A. B., Miyagawa, S. n., Sawa, Y. n., Woo, Y. J. 2017; 16 (1): 142


    Diabetes mellitus is a risk factor for coronary artery disease and diabetic cardiomyopathy, and adversely impacts outcomes following coronary artery bypass grafting. Current treatments focus on macro-revascularization and neglect the microvascular disease typical of diabetes mellitus-induced cardiomyopathy (DMCM). We hypothesized that engineered smooth muscle cell (SMC)-endothelial progenitor cell (EPC) bi-level cell sheets could improve ventricular dysfunction in DMCM.Primary mesenchymal stem cells (MSCs) and EPCs were isolated from the bone marrow of Wistar rats, and MSCs were differentiated into SMCs by culturing on a fibronectin-coated dish. SMCs topped with EPCs were detached from a temperature-responsive culture dish to create an SMC-EPC bi-level cell sheet. A DMCM model was induced by intraperitoneal streptozotocin injection. Four weeks after induction, rats were randomized into 3 groups: control (no DMCM induction), untreated DMCM, and treated DMCM (cell sheet transplant covering the anterior surface of the left ventricle).SMC-EPC cell sheet therapy preserved cardiac function and halted adverse ventricular remodeling, as demonstrated by echocardiography and cardiac magnetic resonance imaging at 8 weeks after DMCM induction. Myocardial contrast echocardiography demonstrated that myocardial perfusion and microvascular function were preserved in the treatment group compared with untreated animals. Histological analysis demonstrated decreased interstitial fibrosis and increased microvascular density in the SMC-EPC cell sheet-treated group.Treatment of DMCM with tissue-engineered SMC-EPC bi-level cell sheets prevented cardiac dysfunction and microvascular disease associated with DMCM. This multi-lineage cellular therapy is a novel, translatable approach to improve microvascular disease and prevent heart failure in diabetic patients.

    View details for PubMedID 29096622

  • A modified technique for orthotopic heart transplantation to minimize warm ischaemic time. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Shudo, Y. n., Wang, H. n., Woo, Y. J. 2017


    Prolonged allograft ischaemic time in heart transplantation adversely impacts the performance of the donor heart in the immediate postoperative period and ultimately results in decreased post-transplant survival. Therefore, optimal surgical technique for heart transplantation should aim to minimize allograft ischaemic time. Here, we report a case of successful orthotopic heart transplantation using a modified technique to reduce allograft ischaemic time and warm ischaemic time.

    View details for PubMedID 29186382

  • Bloodless Repair of Isolated Pulmonary Artery in a Neonate. World journal for pediatric & congenital heart surgery Wang, H., Brewer, M. P., Lai, W. W., Krishnamurthy, G., Chai, P. J. 2016; 7 (1): 112-115


    Pediatric cardiac surgery, especially for small neonates, typically requires blood products to counter hemodilution during cardiopulmonary bypass. Children with congenital heart defects whose families adhere to faith-based proscriptions against blood transfusion therefore represent a challenging surgical population. Here, we report the case of a ten-day-old, 3.6-kg patient of Jehovah's Witness faith, who was diagnosed with unilateral pulmonary artery discontinuity, bilateral patent ductus arteriosus, and an otherwise structurally normal heart. Pulmonary artery reimplantation was successfully performed without giving blood products. This case adds to previous reports of successful bloodless cardiac surgery in neonates and describes the specific strategies that contributed to successful pulmonary artery reimplantation.

    View details for DOI 10.1177/2150135115582071

    View details for PubMedID 26715005

  • Delayed gastric emptying after living donor hepatectomy for liver transplantation. Case reports in transplantation Wang, H., Griesemer, A. D., Parsons, R. F., Graham, J. A., Emond, J. C., Samstein, B. 2014; 2014: 582183-?


    Delayed gastric emptying is a significant postoperative complication of living donor hepatectomy for liver transplantation and may require endoscopic or surgical intervention in severe cases. Although the mechanism of posthepatectomy delayed gastric emptying remains unknown, vagal nerve injury during intraoperative dissection and adhesion formation postoperatively between the stomach and cut liver surface are possible explanations. Here, we present the first reported case of delayed gastric emptying following fully laparoscopic hepatectomy for living donor liver transplantation. Additionally, we also present a case in which symptoms developed after open right hepatectomy, but for which dissection for left hepatectomy was first performed. Through our experience and these two specific cases, we favor a neurovascular etiology for delayed gastric emptying after hepatectomy.

    View details for DOI 10.1155/2014/582183

    View details for PubMedID 25610698

    View details for PubMedCentralID PMC4291134

  • The Effect of Sodium Tanshinone IIA Sulfate and Simvastatin on Elevated Serum Levels of Inflammatory Markers in Patients with Coronary Heart Disease: A Study Protocol for a Randomized Controlled Trial EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE Shang, Q., Wang, H., Li, S., Xu, H. 2013


    Background. Coronary heart disease (CHD) due to atherosclerotic inflammation remains a significant threat to global health despite the success of the lipid-lowering, anti-inflammatory statins. Tanshinone IIA, a potent anti-inflammatory compound derived from Traditional Chinese Medicine (TCM), may be able to supplement statins by further reducing levels of circulating inflammatory markers correlated to cardiovascular risk. Here, we present the protocol of a randomized controlled trial (RCT) that will investigate the synergistic effect of sodium tanshinone IIA sulfate and simvastatin on reducing elevated inflammatory markers in patients with CHD.Seventy-two inpatients with confirmed CHD, elevated serum high-sensitivity C-reactive protein (Hs-CRP) level, and a TCM diagnosis of blood stasis syndrome will be enrolled and randomized 1 : 1 into the control or experimental group. Intervention. All subjects will receive a standard Western therapy including 20 mg simvastatin orally once per evening. Patients in the experimental group will additionally receive a daily 80 mg dose of sodium tanshinone IIA sulfate intravenously, diluted into 250 mL 0.9% NaCl solution. The treatment period will be 14 days. Outcomes. Primary outcome parameter: serum Hs-CRP level. Secondary outcome parameters: other circulating inflammatory markers (including IL-6, TNF α , VCAM-1, CD40, sCD40L, MCP-1, and MMP-9), improvement in symptoms of angina and blood stasis syndrome, and safety. This trial is registered with ChiCTR-TRC-12002361.

    View details for DOI 10.1155/2013/756519

    View details for Web of Science ID 000323265300001

    View details for PubMedID 23983803

    View details for PubMedCentralID PMC3747599