Yasuhiro Shudo, MD, PhD

All Publications

• Extracorporeal membrane oxygenation as a bridge to thoracic multiorgan transplantation. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Heng, E. E., Krishnan, A., Elde, S., Garrison, A., Fawad, M., Ruaengsri, C., Shudo, Y., Guenthart, B. A., Joseph Woo, Y., MacArthur, J. W. 2024

  Abstract

  Extracorporeal membrane oxygenation (ECMO) has emerged as a crucial tool in the care of patients with multiorgan failure, and is increasingly utilized as a bridge to transplantation. While data on ECMO as a bridge to isolated heart and lung transplantation have been described, our emerging experience with ECMO as a bridge to thoracic multiorgan transplantation is not yet well understood. This study aims to investigate temporal trends, utilization, and outcomes in ECMO as a bridge to thoracic multiorgan transplantation.The United Network for Organ Sharing database was used to identify adult patients undergoing thoracic multiorgan transplantation between 1987 and 2022. Exclusion criteria were recipient age <18 and bridging with other mechanical circulatory support including ventricular assist device (VAD) and intra-aortic balloon pump (IABP). Survival analysis was performed to compare outcomes between patients bridged to transplantation with ECMO and those who were not bridged.Of 3,927 patients undergoing thoracic multiorgan transplantation, a total of 203 (5.2%) patients received ECMO as a bridge to transplantation. Among ECMO recipients, patients were most commonly bridged to heart-lung (45.8%), followed by heart-kidney (34.5%), and lung-kidney transplantation (11.8%). At a median follow-up of 35.5 months, unadjusted survival among patients bridged with ECMO was decreased versus multiorgan transplant recipients who were not bridged (p<0.001). With adjusted multivariable Cox regression, ECMO was independently associated with an elevated risk of mortality following multiorgan transplantation (HR 1.56 [1.21-2.02], p<0.01). Among patients surviving past 30 days following transplantation, conditional long-term survival was similar between those bridged with ECMO and those not bridged (p = 0.82).ECMO is increasingly utilized as a bridge to thoracic multiorgan transplantation, and is associated with increased 30 day mortality and decreased long-term survival. In select patients surviving to 30 days following transplantation, similar long-term survival is seen between patients bridged with ECMO and those not bridged.

  View details for DOI 10.1016/j.healun.2024.09.015

  View details for PubMedID 39343333

• Heart-Liver Transplantation Utilizing the En Bloc Technique: A Single-Center Experience Over Two Decades. The Journal of thoracic and cardiovascular surgery Mullis, D. M., Garrison, A., Heng, E., Zhu, Y., Elde, S., Nilkant, R., Boyd, J., Hiesinger, W., Lee, A., Shudo, Y., Gallo, A., Bonham, C. A., Woo, Y. J., MacArthur, J. W. 2024

  Abstract

  Combined heart-liver transplantation (CHLT) is a definitive therapy reserved for patients with concomitant heart failure and advanced liver disease. A limited number of centers perform CHLT, and even fewer use the en bloc implantation technique. This study 1) reviews clinical outcomes and immunoprotective effects following CHLT, and 2) describes our institution's experience of over two decades using the en bloc technique.All patients who underwent CHLT at our institution between January 2003 and July 2023 were identified. Recipient and donor characteristics, operative details, and clinical outcomes were assessed. Kaplan-Meier analysis was performed to evaluate survival following CHLT.A total of 20 patients underwent CHLT using the en bloc technique at our institution between January 2003 and July 2023. At a median follow-up of 3.8 years for patients who survived the perioperative period (n=18), estimated survival at 1- and 5-years was 94% and 75%, respectively. There was 100% freedom from acute moderate rejection, acute severe rejection, and chronic rejection in all patients. No patients required re-transplantation due to rejection.CHLT is a definitive therapy reserved for patients with multi-organ dysfunction. At our institution, the en bloc technique is the preferred operative approach, as it minimizes cardiac insult, requires fewer anastomoses, minimizes cold ischemia time, and allows for rapid correction of coagulopathy. Overall survival for this cohort is excellent. Episodes of acute rejection were rarely observed, providing further support that the liver may serve an immunoprotective role in multi-organ transplantation.

  View details for DOI 10.1016/j.jtcvs.2024.08.031

  View details for PubMedID 39187122

• Survival, Function, and Immune Profiling after Beating Heart Transplantation. The Journal of thoracic and cardiovascular surgery Krishnan, A., Elde, S., Ruaengsri, C., Guenthart, B. A., Zhu, Y., Fawad, M., Lee, A., Currie, M., Ma, M. R., Hiesinger, W., Shudo, Y., MacArthur, J. W., Woo, Y. J. 2024

  Abstract

  Ex-vivo normothermic perfusion of cardiac allografts has expanded the donor pool. Utilizing a beating heart implantation method avoids the second cardioplegic arrest and subsequent ischemia reperfusion injury typically associated with ex-vivo heart perfusion. We sought to describe our institutional experience with beating heart transplantation.This was a single-institution retrospective study of adult patients who underwent heart transplantation utilizing ex-vivo heart perfusion (EVHP) and a beating heart implantation technique between October 2022 and March 2024. Primary outcomes of interest included survival, initiation of mechanical circulatory support, and rejection. A sub-analysis of our institutional series of non-beating DCD heart transplantation was also performed.Twenty-four patients underwent isolated heart transplantation with the use of ex-vivo heart perfusion and beating heart implantation between October 2022 and March 2024; 21 (87.5%) received hearts from DCD donors, and 3 (12.5%) patients received hearts from DBD donors. Median follow-up was 192 days (interquartile range of 124-253.5 days), and 23 out of 24 patients (95.8%) were alive at last follow up. No patients required initiation of mechanical circulatory support. The majority of patients had pathological grade 0 rejection at the time of biopsy (n=16, 66.7%), and the median cell-free DNA percent was 0.04% (interquartile range 0.04-0.09). The rate of mechanical circulatory support initiation in the 22-patient non-beating DCD heart transplant cohort was significantly higher at 36.4% (p<0.005).A beating heart implantation technique can be used on DCD and DBD hearts on EVHP and is associated with excellent survival and low levels of rejection.

  View details for DOI 10.1016/j.jtcvs.2024.07.058

  View details for PubMedID 39111693

• 3D Imaging Reveals Complex Microvascular Remodeling in the Right Ventricle in Pulmonary Hypertension. Circulation research Ichimura, K., Boehm, M., Andruska, A. M., Zhang, F., Schimmel, K., Bonham, S., Kabiri, A., Kheyfets, V. O., Ichimura, S., Reddy, S., Mao, Y., Zhang, T., Wang, G., Santana, E. J., Tian, X., Essafri, I., Vinh, R., Tian, W., Nicolls, M. R., Yajima, S., Shudo, Y., MacArthur, J. W., Woo, Y. J., Metzger, R. J., Spiekerkoetter, E. 2024

  Abstract

  Pathogenic concepts of right ventricular (RV) failure in pulmonary arterial hypertension focus on a critical loss of microvasculature. However, the methods underpinning prior studies did not take into account the 3-dimensional (3D) aspects of cardiac tissue, making accurate quantification difficult. We applied deep-tissue imaging to the pressure-overloaded RV to uncover the 3D properties of the microvascular network and determine whether deficient microvascular adaptation contributes to RV failure.Heart sections measuring 250-µm-thick were obtained from mice after pulmonary artery banding (PAB) or debanding PAB surgery and properties of the RV microvascular network were assessed using 3D imaging and quantification. Human heart tissues harvested at the time of transplantation from pulmonary arterial hypertension cases were compared with tissues from control cases with normal RV function.Longitudinal 3D assessment of PAB mouse hearts uncovered complex microvascular remodeling characterized by tortuous, shorter, thicker, highly branched vessels, and overall preserved microvascular density. This remodeling process was reversible in debanding PAB mice in which the RV function recovers over time. The remodeled microvasculature tightly wrapped around the hypertrophied cardiomyocytes to maintain a stable contact surface to cardiomyocytes as an adaptation to RV pressure overload, even in end-stage RV failure. However, microvasculature-cardiomyocyte contact was impaired in areas with interstitial fibrosis where cardiomyocytes displayed signs of hypoxia. Similar to PAB animals, microvascular density in the RV was preserved in patients with end-stage pulmonary arterial hypertension, and microvascular architectural changes appeared to vary by etiology, with patients with pulmonary veno-occlusive disease displaying a lack of microvascular complexity with uniformly short segments.3D deep tissue imaging of the failing RV in PAB mice, pulmonary hypertension rats, and patients with pulmonary arterial hypertension reveals complex microvascular changes to preserve the microvascular density and maintain a stable microvascular-cardiomyocyte contact. Our studies provide a novel framework to understand microvascular adaptation in the pressure-overloaded RV that focuses on cell-cell interaction and goes beyond the concept of capillary rarefaction.

  View details for DOI 10.1161/CIRCRESAHA.123.323546

  View details for PubMedID 38770652

• Optimizing Donor Heart Utilization Amidst Organ Shortage: Feasibility of Using Hearts Post-Long CPR. The Annals of thoracic surgery Leon, M., Shudo, Y. 2024

  View details for DOI 10.1016/j.athoracsur.2024.03.038

  View details for PubMedID 38621652

• Impact of C-reactive Protein on Anticoagulation Monitoring in Extracorporeal Membrane Oxygenation. Journal of cardiothoracic and vascular anesthesia Madhok, J., O'Donnell, C., Jin, J., Owyang, C. G., Weimer, J. M., Pashun, R. A., Shudo, Y., McNulty, J., Chadwick, B., Ruoss, S. J., Rao, V. K., Zehnder, J. L., Hsu, J. L. 2024

  Abstract

  To evaluate the impact of inflammation on anticoagulation monitoring for patients supported with extracorporeal membrane oxygenation (ECMO).Prospective single-center cohort study.University-affiliated tertiary care academic medical center.Adult venovenous and venoarterial ECMO patients anticoagulated with heparin/ MEASUREMENTS AND MAIN RESULTS: C-Reactive protein (CRP) was used as a surrogate for overall inflammation. The relationship between CRP and the partial thromboplastin time (PTT, seconds) was evaluated using a CRP-insensitive PTT assay (PTT-CRP) in addition to measurement using a routine PTT assay. Data from 30 patients anticoagulated with heparin over 371 ECMO days was included. CRP levels (mg/dL) were significantly elevated (median, 17.2; interquartile range [IQR], 9.2-26.1) and 93% of patients had a CRP of ≥5. The median PTT (median 58.9; IQR, 46.9-73.3) was prolonged by 11.3 seconds compared with simultaneously measured PTT-CRP (median, 47.6; IQR, 40.1-55.5; p < 0.001). The difference between PTT and PTT-CRP generally increased with CRP elevation from 2.7 for a CRP of <5.0 to 13.0 for a CRP between 5 and 10, 17.7 for a CRP between 10 and 15, and 15.1 for a CRP of >15 (p < 0.001). In a subgroup of patients, heparin was transitioned to argatroban, and a similar effect was observed (median PTT, 62.1 seconds [IQR, 53.0-78.5 seconds] vs median PTT-CRP, 47.6 seconds [IQR, 41.3-57.7 seconds]; p < 0.001).Elevations in CRP are common during ECMO and can falsely prolong PTT measured by commonly used assays. The discrepancy due to CRP-interference is important clinically given narrow PTT targets and may contribute to hematological complications.

  View details for DOI 10.1053/j.jvca.2024.04.006

  View details for PubMedID 38960805

• Eliminating Ischemia: Sustaining Cardiac Function During Donor Procurement Fawad, M., Zhu, Y., Elde, S., Krishnan, A., McNulty, J., Chadwick, B., Wang, Y., Lu, C., Massey, M., Trope, W., Simmons, J., Lee, S., Stark, C., Walsh, S., Venkatesh, A., Vergel, M., Oh, S. E., Huynh, C., Yang, J., Cywinska, G., MacArthur, J., Shudo, Y., Ruaengsri, C., Woo, J., Guenthart, B. A. ELSEVIER SCIENCE INC. 2024: S158

  View details for Web of Science ID 001281353100300

• ECMO as a Bridge to Thoracic Multi-Organ Transplantation Heng, E. E., Krishnan, A., Elde, S., Garrison, A., Fawad, M., Ruaengsri, C., Shudo, Y., Guenthart, B. A., Woo, J., MacArthur, J. W. ELSEVIER SCIENCE INC. 2024: S29-S30

  View details for Web of Science ID 001281353100042

• Impact of Total Allograft Ischemic Time on Heart-Lung Transplantation Outcomes in the United States Zhu, Y., He, H., Woo, Y., Shudo, Y. ELSEVIER SCIENCE INC. 2024: S444

  View details for Web of Science ID 001281353102158

• An Ocean of Difference? Donor and Recipient Risk Factor Perception from a Cross-National Survey Guenther, S. P., Khush, K. K., Hoepner, L., Schaeper, K., Fox, H., Hiesinger, W., Shudo, Y., Morshuis, M., Woo, J., Teuteberg, J., Gummert, J. F., Schramm, R., Wayda, B. J. ELSEVIER SCIENCE INC. 2024: S220

  View details for Web of Science ID 001281353101103

• Organ Care System Heart Perfusion (OHP) Registry Annual Report Donation After Circulatory Death Heart Transplant Outcomes Daneshmand, M. A., Schroder, J., D'Alessandro, D., Pham, S., Lozonschi, L., Couper, G., Shah, A., Pal, J., Klein, L., Esmailian, F., Davis, R., Villavicencio, M., Shaffer, A., Sun, B., Takeda, K., Pham, D., Malyala, R., Mallidi, H., Haft, J., Meyer, D., Durham, L., Goldstein, D., Funamoto, M., Ohira, S., Kaczorowski, D., Stehlik, J., Pinney, S., Farr, M., Milano, C., Shudo, Y. ELSEVIER SCIENCE INC. 2024: S123-S124

  View details for Web of Science ID 001281353100231

• Use of Hearts from SARS-CoV-2 Positive Donors for Transplantation: An Analysis of Trends, Provider Perceptions, Safety, and Outcomes Guenther, S. P., Wadewitz, J., Wayda, B. J., Rogge, A., Fox, H., Costard-Jaeckle, A., Shudo, Y., Hiesinger, W., Morshuis, M., Woo, J., Teuteberg, J., Schramm, R., Gummert, J. F., Khush, K. K., Rahmel, A. ELSEVIER SCIENCE INC. 2024: S233-S234

  View details for Web of Science ID 001281353101130

• Mobile Thermoelectric Cooler for 10 °C Lung Preservation Fawad, M., Massey, M., Lu, C., Krishnan, A., Elde, S., Trope, W., Wang, Y., Simmons, J., Stark, C., Cywinska, G., MacArthur, J., Shudo, Y., Ruaengsri, C., Woo, J., Guenthart, B. A. ELSEVIER SCIENCE INC. 2024: S275

  View details for Web of Science ID 001281353101219

• Dot Your I's and Check Your T's? Impact of Various T Cell Monitoring Methods on Heart Transplant Outcomes Henricksen, E., Khush, K., Lee, R., Intieri, T., Luikart, H., Kim, D., Skoda, A., Subramanian, A., Wayda, B., Zhang, M. B., Imai, R., Le, T., Wang, U., Moayedi, Y., Sallam, K., Hsiao, S., Haddad, F., Shudo, Y., Teuteberg, J. ELSEVIER SCIENCE INC. 2024: S103-S104

  View details for Web of Science ID 001281353100193

• Organ Care System Heart Perfusion (OHP) Registry Annual Report - DBD Heart Transplants Clinical Outcomes Villavicencio, M., Klein, L., Schroder, J., Couper, G., Ohira, S., Davis, R., Haft, J., Pham, S., Daneshmand, M., Pham, D., D'Alessandro, D., Sun, B., Goldstein, D., Meyer, D., Lozonschi, L., Malyala, R., Esmailian, F., Mallidi, H., Takeda, K., Spencer, P., Kaczorowski, D., Funamoto, M., Durham, L., Shudo, Y., Shaffer, A., Stehlik, J., Pinney, S., Farr, M., Milano, C., Pal, J. ELSEVIER SCIENCE INC. 2024: S159-S160

  View details for Web of Science ID 001281353100303

• Cutting to the Bone: Impact of Redo Sternotomy on Outcome of Adult Heart Transplant Hoang, J. D., Henricksen, E. J., Varshney, A., Sanchez, M., Chen, C., Castillo, F., Koyano, T., Teuteberg, J., Khush, K., Luikart, H., Subramanian, A., Moayedi, Y., Tayyar, R., Shudo, Y. ELSEVIER SCIENCE INC. 2024: S571-S572

  View details for Web of Science ID 001281353102438

• Improved Post-Transplant Outcomes in Blood Group O Recipients Through Controlled Hypothermic Preservation Rodrigo, M., Silvestry, S., Shudo, Y., Schroder, J., Vidic, A., Takeda, K., Meyer, D., D'Alessandro, D. ELSEVIER SCIENCE INC. 2024: S568

  View details for Web of Science ID 001281353102431

• Improved 2-Year Heart Transplant Survival with Moderate Hypothermic Donor Heart Preservation in the Guardian Heart Registry Silvestry, S., Meyer, D., Pham, S., Jacobs, J. P., Shudo, Y., Schroder, J., Leacche, M., Sciortino, C., Copeland, H., Rodrigo, M. E., Takeda, K., Kawabori, M., Mahesh, B., Klein, L., Vidic, A., Patel, S., D'Alessandro, D. ELSEVIER SCIENCE INC. 2024: S67-S68

  View details for Web of Science ID 001281353100124

• Real-World Clinical Outcomes of DCD Heart Transplantation from the OCS Heart Perfusion (OHP) Registry: Benchmarking to Other Preservation Methods Milano, C., Schroder, J., Daneshmand, M., D'Alessandro, D., Pham, S., Couper, G., Shah, A., Pal, J., Klein, L., Esmailian, F., Davis, R., Villavicencio, M., Shaffer, A., Sun, B., Takeda, K., Pham, D., Malyala, R., Mallidi, H., Haft, J., Meyer, D., Durham, L., Goldstein, D., Funamoto, M., Ohira, S., Kaczorowski, D., Shudo, Y., Stehlik, J., Pinney, S., Farr, M., Lozonschi, L. ELSEVIER SCIENCE INC. 2024: S12-S13

  View details for Web of Science ID 001281353100007

• Failure to Rescue in Heart Lung Transplantation: Progress Over 30 Years Heng, E. E., Elde, S., Krishnan, A., Garrison, A., Fawad, M., Ruaengsri, C., Shudo, Y., Guenthart, B. A., Woo, J., MacArthur, J. W. ELSEVIER SCIENCE INC. 2024: S264

  View details for Web of Science ID 001281353101195

• Reduced Risk of Cardiovascular-Related Death Associated with Moderate Hypothermic Donor Heart Preservation in the Guardian Heart Registry Zuckermann, A., Boston, U., Esteve, A., Jacobs, J. P., Pham, S., Takeda, K., Kawabori, M., Shudo, Y., Vidic, A., Leacche, M., Rodrigo, M., Meyer, D., Venkateswaran, R., Karner, B., Munguira, J., Schroder, J., Mahesh, B., Silvestry, S., D'Alessandro, D. ELSEVIER SCIENCE INC. 2024: S157-S158

  View details for Web of Science ID 001281353100299

• Impact of Controlled Hypothermic Preservation on Outcomes Following Heart Transplantation. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation D'Alessandro, D., Schroder, J., Meyer, D. M., Vidic, A., Shudo, Y., Silvestry, S., Leacche, M., Sciortino, C. M., Rodrigo, M., Pham, S. M., Copeland, H., Jacobs, J. P., Kawabori, M., Takeda, K., Zuckermann, A. 2024

  Abstract

  Severe primary graft dysfunction (PGD) is a major cause of early mortality after heart transplant. but the impact of donor organ preservation conditions on severity of PGD and survival have not been well characterized.Data from US adult heart-transplant recipients in the GUARDIAN-Heart registry (NCT04141605) were analyzed to quantify PGD severity (stratified by ISHLT definition), mortality, and associated risk factors. The independent contributions of organ-preservation method (traditional ice storage versus controlled hypothermic preservation) and ischemic time were analyzed using propensity matching and logistic regression.Among 1,061 US adult heart transplants performed between October 2015 and December 2022, controlled hypothermic preservation was associated with a significant reduction in the incidence of severe PGD compared to ice (6.6% (37/559) versus 10.4% (47/452), p=0.039). Following propensity matching, severe PGD was reduced by 50% (6.0% (17/281) versus 12.1% (34/281) respectively; p=0.018). The Kaplan-Meier terminal probability of 1-year mortality was 4.2% for recipients without PGD, 7.2% for mild or moderate PGD, and 32.1%, for severe PGD (p<0.001). The probability of severe PGD increased for both cohorts with longer ischemic time, but donor hearts stored on ice were more likely to develop severe PGD at all ischemic times compared to controlled hypothermic preservation.Severe PGD is the deadliest complication of heart transplantation and is associated with a 7.8-fold increase in probability of 1-year mortality. Controlled hypothermic preservation significantly attenuates the risk of severe PGD and is a simple yet highly effective tool for mitigating post-transplant morbidity.

  View details for DOI 10.1016/j.healun.2024.03.010

  View details for PubMedID 38503386

• 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

  Abstract

  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

• Increasing Utilization of Extended Criteria Donor Hearts for Transplantation JACC-HEART FAILURE Schroder, J. N., Patel, C. B., DeVore, A. D., Casalinova, S., Koomalsingh, K. J., Shah, A. S., Anyanwu, A. C., DAlessandro, D. A., Mudy, K., Sun, B., Strueber, M., Khaghani, A., Shudo, Y., Esmailian, F., Liao, K., Pagani, F. D., Silvestry, S., Wang, I., Salerno, C. T., Absi, T. S., Madsen, J. C., Mancini, D., Fiedler, A. G., Milano, C. A., Smith, J. W. 2024; 12 (3): 438-447

  View details for DOI 10.1016/j.polymer.2024.126829

  View details for Web of Science ID 001208377500001

• 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

  Abstract

  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

• Outcomes in Heart Transplant Recipients by Bridge to Transplant Strategy When Using the SherpaPak Cardiac Transport System. ASAIO journal (American Society for Artificial Internal Organs : 1992) Silvestry, S., Leacche, M., Meyer, D. M., Shudo, Y., Kawabori, M., Mahesh, B., Zuckermann, A., D'Alessandro, D., Schroder, J. 2024

  Abstract

  The last several years have seen a rise in use of mechanical circulatory support (MCS) to bridge heart transplant recipients. A controlled hypothermic organ preservation system, the SherpaPak Cardiac Transport System (SCTS), was introduced in 2018 and has grown in utilization with reports of improved posttransplant outcomes. The Global Utilization And Registry Database for Improved heArt preservatioN (GUARDIAN)-Heart registry is an international, multicenter registry assessing outcomes after transplant using the SCTS. This analysis examines outcomes in recipients bridged with various MCS devices in the GUARDIAN-Heart Registry. A total of 422 recipients with donor hearts transported using SCTS were included and identified. Durable ventricular assist devices (VADs) were used exclusively in 179 recipients, temporary VADs or intra-aortic balloon pump (IABP) in 197, and extracorporeal membrane oxygenation (ECMO) in 14 recipients. Average ischemic times were over 3.5 hours in all cohorts. Severe primary graft dysfunction (PGD) posttransplant increased across groups (4.5% VAD, 5.1% temporary support, 21.4% ECMO), whereas intensive care unit (ICU) length of stay (18.2 days) and total hospital stay (39.4 days) was longer in the ECMO cohort than the VAD and IABP groups. A comparison of outcomes of MCS bridging in SCTS versus traditional ice revealed significantly lower rates of both moderate/severe right ventricular (RV) dysfunction and severe PGD in the SCTS cohort; however, upon propensity matching only the reductions in moderate/severe RV dysfunction were statistically significant. Use of SCTS in transplant recipients with various bridging strategies results in excellent outcomes.

  View details for DOI 10.1097/MAT.0000000000002137

  View details for PubMedID 38300893

• Increasing Utilization of Extended Criteria Donor Hearts for Transplantation: The OCS Heart EXPAND Trial. JACC. Heart failure Schroder, J. N., Patel, C. B., DeVore, A. D., Casalinova, S., Koomalsingh, K. J., Shah, A. S., Anyanwu, A. C., D'Alessandro, D. A., Mudy, K., Sun, B., Strueber, M., Khaghani, A., Shudo, Y., Esmailian, F., Liao, K., Pagani, F. D., Silvestry, S., Wang, I., Salerno, C. T., Absi, T. S., Madsen, J. C., Mancini, D., Fiedler, A. G., Milano, C. A., Smith, J. W. 2024

  Abstract

  BACKGROUND: Extended criteria donor (ECD) hearts available with donation after brain death (DBD) are underutilized for transplantation due to limitations of cold storage.OBJECTIVES: This study evaluated use of an extracorporeal perfusion system on donor heart utilization and post-transplant outcomes in ECD DBD hearts.METHODS: In this prospective, single-arm, multicenter study, adult heart transplant recipients received ECD hearts using an extracorporeal perfusion system if hearts met study criteria. The primary outcome was a composite of 30-day survival and absence of severe primary graft dysfunction (PGD). Secondary outcomes were donor heart utilization rate, 30-day survival, and incidence of severe PGD. The safety outcome was the mean number of heart graft-related serious adverse events within 30days. Additional outcomes included survival through 2 years benchmarked to concurrent nonrandomized control subjects.RESULTS: A total of 173 ECD DBD hearts were perfused; 150 (87%) were successfully transplanted; 23 (13%) did not meet study transplantation criteria. At 30days, 92% of patients had survived and had no severe PGD. The 30-day survival was 97%, and the incidence of severe PGD was 6.7%. The mean number of heart graft-related serious adverse events within 30days was 0.17 (95%CI: 0.11-0.23). Patient survival was 93%, 89%, and 86% at 6, 12, and 24months, respectively, and was comparable with concurrent nonrandomized control subjects.CONCLUSIONS: Use of an extracorporeal perfusion system resulted in successfully transplanting 87% of donor hearts with excellent patient survival to 2 years post-transplant and low rates of severe PGD. The ability to safely use ECD DBD hearts could substantially increase the number of heart transplants and expand access to patients in need. (International EXPAND Heart Pivotal Trial [EXPANDHeart]; NCT02323321; Heart EXPAND Continued Access Protocol; NCT03835754).

  View details for DOI 10.1016/j.jchf.2023.11.015

  View details for PubMedID 38276933

• Risk Of Rv Dysfunction Following Heart Transplantation: Donor Organ Temperature Matters! Uriel, N., Teuteberg, J., Silvestry, S., Leacche, M., Schroder, J., Shudo, Y., Meyer, D., Kawabori, M., Takeda, K., Jacoski, M., D'Alessandro, D., Devore, A. CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS. 2024: 136

  View details for Web of Science ID 001162343100043

• Recipient Outcomes with Extended Criteria Donors Using Advanced Heart Preservation: An Analysis of the GUARDIAN Heart Registry. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Moayedifar, R., Shudo, Y., Kawabori, M., Silvestry, S., Schroder, J., Meyer, D. M., Jacobs, J. P., D'Alessandro, D., Zuckermann, A. 2023

  Abstract

  The prevalence of end stage heart failure and patients that could benefit from heart transplantation requires an expansion of the donor pool, relying on the transplant community to continually re-evaluate and expand the use of extended criteria donor organs. Introduction of new technologies such as the Paragonix SherpaPak Cardiac Transport System aids in this shift. We seek to analyze the impact of the SherpaPak system on recipient outcomes who receive extended criteria organs in the GUARDIAN Heart Registry.Between October 2015-December 2022, 1,113 adults from 15 US centers receiving donor hearts utilizing either SherpaPak (N=560) or conventional ice storage (Ice, N=453) were analyzed from the GUARDIAN-Heart registry using summary statistics. A previously published set of criteria was used to identify extended criteria donors, which included 193 SherpaPak and 137 ice.There were a few baseline differences among recipients in the 2 cohorts, most notably IMPACT Scores, distance traveled and total ischemic time were significantly greater in SherpaPak, and significantly more donor hearts in the SherpaPak cohort had >4 hours total ischemia time. Post-transplant MCS utilization (SherpaPak 22.3% vs. ice 35.0%, p=0.012) and new ECMO/VAD (SherpaPak 7.8% vs. ice 15.3%, p=0.033) was significantly reduced, and the rate of severe PGD (SherpaPak 6.2% vs. ice 13.9%, p=0.022) was significantly reduced by over 50% in hearts preserved using SherpaPak. One-year survival between cohorts was similar (SherpaPak 92.9% vs. ice 89.6%, p=0.27).This subgroup analysis demonstrates that SherpaPak can be safely used to utilize extended criteria donors, with low severe PGD rates.

  View details for DOI 10.1016/j.healun.2023.12.013

  View details for PubMedID 38163452

• A Paradigm Shift in Heart Preservation: Improved Post-transplant Outcomes in Recipients of Donor Hearts Preserved with the SherpaPak System. ASAIO journal (American Society for Artificial Internal Organs : 1992) Shudo, Y., Leacche, M., Copeland, H., Silvestry, S., Pham, S. M., Molina, E., Schroder, J. N., Sciortino, C. M., Jacobs, J. P., Kawabori, M., Meyer, D. M., Zuckermann, A., D'Alessandro, D. A. 2023

  Abstract

  Traditional ice storage has been the historic standard for preserving donor's hearts. However, this approach provides variability in cooling, increasing risks of freezing injury. To date, no preservation technology has been reported to improve survival after transplantation. The Paragonix SherpaPak Cardiac Transport System (SCTS) is a controlled hypothermic technology clinically used since 2018. Real-world evidence on clinical benefits of SCTS compared to conventional ice cold storage (ICS) was evaluated. Between October 2015 and January 2022, 569 US adults receiving donor hearts preserved and transported either in SCTS (n = 255) or ICS (n = 314) were analyzed from the Global Utilization And Registry Database for Improved heArt preservatioN (GUARDIAN-Heart) registry. Propensity matching and a subgroup analysis of >240 minutes ischemic time were performed to evaluate comparative outcomes. Overall, the SCTS cohort had significantly lower rates of severe primary graft dysfunction (PGD) (p = 0.03). When propensity matched, SCTS had improving 1-year survival (p = 0.10), significantly lower rates of severe PGD (p = 0.011), and lower overall post-transplant MCS utilization (p = 0.098). For patients with ischemic times >4 hours, the SCTS cohort had reduced post-transplant MCS utilization (p = 0.01), reduced incidence of severe PGD (p = 0.005), and improved 30-day survival (p = 0.02). A multivariate analysis of independent risk factors revealed that compared to SCTS, use of ice results in a 3.4-fold greater chance of severe PGD (p = 0.014). Utilization of SCTS is associated with a trend toward increased post-transplant survival and significantly lower severe PGD and MCS utilization. These findings fundamentally challenge the decades-long status quo of transporting donor hearts using ice.

  View details for DOI 10.1097/MAT.0000000000002036

  View details for PubMedID 37678260

• Case report: Heart retransplant from a donor after circulatory death and extended transport period with normothermic perfusion. Frontiers in cardiovascular medicine Kasinpila, P., Ruaengsri, C., Koyano, T., Shudo, Y. 2023; 10: 1212886

  Abstract

  A 55-year-old man with end-stage heart failure, who had an orthotopic heart transplant 21 years prior, underwent heart retransplantation using a heart from a donor with circulatory death in a distant location and an extended transport period with normothermic ex vivo perfusion. Owing to the persistent and worsening shortage of donor hearts, this case illustrates that expanding the donor acceptance criteria to include more distant donor locations and enrolling recipients with extended criteria (e.g., heart retransplantation) is feasible.

  View details for DOI 10.3389/fcvm.2023.1212886

  View details for PubMedID 37636312

  View details for PubMedCentralID PMC10457678

• Outcomes of Patients Undergoing Combined Heart-Kidney Transplantation With or Without Prior Ventricular Assist Device. Transplantation proceedings Currie, M., Leipzig, M., Kaghazchi, A., Zhu, Y., Shudo, Y., Woo, Y. J. 2023

  Abstract

  BACKGROUND: Both combined heart-kidney transplantation and ventricular assist devices (VADs) pose significant challenges, including sensitization, immunosuppressive treatment, and infrastructure demands. Despite these challenges, we hypothesized that the recipients of combined heart-kidney transplants with and without VADs would have equivalent survival. We aimed to compare the survival of heart-kidney transplant recipients with and without prior VAD placement.METHODS: We retrospectively analyzed all patients enrolled in the United Network for Organ Sharing database who underwent heart-kidney transplants. We created a matched cohort of patients undergoing heart-kidney transplantation with or without prior VAD using 1:1 nearest propensity-score matching with preoperative variables.RESULTS: In the propensity-matched cohort, 399 patients underwent heart-kidney transplantation with prior VAD, and 399 underwent heart-kidney transplantation without prior VAD. The estimated survival of heart--kidney recipients with prior VAD was 84.8% at one year, 81.2% at 3 years, and 75.3% at 5 years. The estimated survival of heart-kidney recipients without prior VAD was 86.8.7% at one year, 84.0% at 3 years, and 78.8% at 5 years. There was no statistically significant difference in the survival of heart-kidney transplant recipients with or without prior VAD at one year (P=.42; Figure 2), 3 years (P=.34), or 5 years (P=.30).CONCLUSION: Despite the increased challenge of heart-kidney transplantation in recipients with prior VAD, we demonstrated that these patients have similar survival to those who underwent heart-kidney transplantation without previous VAD placement.

  View details for DOI 10.1016/j.transproceed.2023.04.037

  View details for PubMedID 37393169

• Transplantation Outcomes with Donor Hearts after Circulatory Death. The New England journal of medicine Schroder, J. N., Patel, C. B., DeVore, A. D., Bryner, B. S., Casalinova, S., Shah, A., Smith, J. W., Fiedler, A. G., Daneshmand, M., Silvestry, S., Geirsson, A., Pretorius, V., Joyce, D. L., Um, J. Y., Esmailian, F., Takeda, K., Mudy, K., Shudo, Y., Salerno, C. T., Pham, S. M., Goldstein, D. J., Philpott, J., Dunning, J., Lozonschi, L., Couper, G. S., Mallidi, H. R., Givertz, M. M., Pham, D. T., Shaffer, A. W., Kai, M., Quader, M. A., Absi, T., Attia, T. S., Shukrallah, B., Sun, B. C., Farr, M., Mehra, M. R., Madsen, J. C., Milano, C. A., D'Alessandro, D. A. 2023; 388 (23): 2121-2131

  Abstract

  Data showing the efficacy and safety of the transplantation of hearts obtained from donors after circulatory death as compared with hearts obtained from donors after brain death are limited.We conducted a randomized, noninferiority trial in which adult candidates for heart transplantation were assigned in a 3:1 ratio to receive a heart after the circulatory death of the donor or a heart from a donor after brain death if that heart was available first (circulatory-death group) or to receive only a heart that had been preserved with the use of traditional cold storage after the brain death of the donor (brain-death group). The primary end point was the risk-adjusted survival at 6 months in the as-treated circulatory-death group as compared with the brain-death group. The primary safety end point was serious adverse events associated with the heart graft at 30 days after transplantation.A total of 180 patients underwent transplantation; 90 (assigned to the circulatory-death group) received a heart donated after circulatory death and 90 (regardless of group assignment) received a heart donated after brain death. A total of 166 transplant recipients were included in the as-treated primary analysis (80 who received a heart from a circulatory-death donor and 86 who received a heart from a brain-death donor). The risk-adjusted 6-month survival in the as-treated population was 94% (95% confidence interval [CI], 88 to 99) among recipients of a heart from a circulatory-death donor, as compared with 90% (95% CI, 84 to 97) among recipients of a heart from a brain-death donor (least-squares mean difference, -3 percentage points; 90% CI, -10 to 3; P<0.001 for noninferiority [margin, 20 percentage points]). There were no substantial between-group differences in the mean per-patient number of serious adverse events associated with the heart graft at 30 days after transplantation.In this trial, risk-adjusted survival at 6 months after transplantation with a donor heart that had been reanimated and assessed with the use of extracorporeal nonischemic perfusion after circulatory death was not inferior to that after standard-care transplantation with a donor heart that had been preserved with the use of cold storage after brain death. (Funded by TransMedics; ClinicalTrials.gov number, NCT03831048.).

  View details for DOI 10.1056/NEJMoa2212438

  View details for PubMedID 37285526

• 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

• World's first en bloc heart-lung transplantation using the paragonix lungguard donor preservation system. Journal of cardiothoracic surgery Neto, D., Guenthart, B., Shudo, Y., Currie, M. E. 2023; 18 (1): 131

  Abstract

  We present the first en bloc heart-lung donor transplant procurement using the Paragonix LUNGguard™ donor preservation system. This system offers reliable static hypothermic conditions designed to prevent major complications such as cold ischemic injury, uneven cooling and physical damage. While this represents a single case, the encouraging results warrant further investigation.

  View details for DOI 10.1186/s13019-023-02281-7

  View details for PubMedID 37041582

  View details for PubMedCentralID PMC10091844

• Successful Heart Transplantation Using a Portable Normothermic Ex-Vivo Donor Heart Preservation System for Extended Criteria Donor after Circulatory Death: A Case Series with Extended Perfusion Times Ruaengsri, C., Shudo, Y., Malki, A., Neto, D., Chen, R., Bethencourt, D., Hiesinger, W., MacArthur, J., Currie, M., Boyd, J., Guenthart, B., Lee, A., Woo, J. ELSEVIER SCIENCE INC. 2023: S467-S468

  View details for Web of Science ID 000992480601308

• Results from over 800 Transplant Recipients Enrolled in the Guardian Heart Registry D'Alessandro, D., Shudo, Y., Meyer, D., Silvestry, S., Leacche, M., Sciortino, C., Rodrigo, M., Pham, S. M., Jacobs, J. P., Takeda, K., Copeland, H., Vidic, A., Kawabori, M., Schroder, J. ELSEVIER SCIENCE INC. 2023: S63-S64

  View details for Web of Science ID 000992480600120

• Can Controlled Hypothermic Preservation Provide Clinical Benefits in the Setting of Shorter Ischemic Times Prior to Heart Transplant Meyer, D., Shudo, Y., Schroder, J., D'Alessandro, D., Silvestry, S., Sciortino, C., Pham, S. M., Rodrigo, M., Jacobs, J. P., Kawabori, M., Takeda, K., Leacche, M. ELSEVIER SCIENCE INC. 2023: S189

  View details for Web of Science ID 000992480600393

• Improved Outcomes in Older Recipients Undergoing Transplant Using the Sherpapak System: A Subgroup Analysis of the Guardian Heart Registry Copeland, H., Leacche, M., D'Alessandro, D., Sciortino, C., Schroder, J., Pham, S. M., Rodrigo, M., Silvestry, S., Kawabori, M., Shudo, Y., Meyer, D. ELSEVIER SCIENCE INC. 2023: S288

  View details for Web of Science ID 000992480600636

• How Long Can We Go? Redefining the Upper Limit of Ischemic Times for Hypothermic Donor Heart Preservation Takeda, K., Silvestry, S., Schroder, J., D'Alessandro, D., Leacche, M., Sciortino, C., Pham, S. M., Vidic, A., Meyer, D., Kawabori, M., Shudo, Y. ELSEVIER SCIENCE INC. 2023: S278

  View details for Web of Science ID 000992480600613

• Recipient Outcomes with Extended Criteria Donors: An Analysis of the Guardian Heart Registry Moayedifar, R., Shudo, Y., Kawabori, M., Silvestry, S., Schroder, J., Meyer, D., D'Alessandro, D., Zuckermann, A. ELSEVIER SCIENCE INC. 2023: S31-S32

  View details for Web of Science ID 000992480600050

• Intracellular Cardiac Preservation Solution May Have Superior Clinical Outcomes to Extracellular Solution for Adult Heart Transplantation Chen, R. J., Ruaengsri, C., He, H., Shudo, Y., Neto, D., Malki, A., Bethencourt, D. M., Theodore, P. R., Woo, J. ELSEVIER SCIENCE INC. 2023: S119

  View details for Web of Science ID 000992480600240

• Validating the 2014 Consensus Primary Graft Definition: An Analysis on the 1,056 Patients from the Multi-Center Guardian Registry Zuckermann, A., Jacobs, J. P., Shudo, Y., Meyer, D., Silvestry, S., Leacche, M., Sciortino, C., Rodrigo, M., Pham, S., Takeda, K., Copeland, H., Vidic, A., Kawabori, M., Boston, U., Bustamante-Munguira, J., Esteve, A., Venkateswaran, R., Schroder, J., D'Alessandro., D. ELSEVIER SCIENCE INC. 2023: S72-S73

  View details for Web of Science ID 000992480600138

• Leveraging Advanced Hypothermic Preservation to Achieve Transplant Program Goals Schroder, J., Leacche, M., Sciortino, C., Shudo, Y., Rodrigo, M., Meyer, D., Kawabori, M., D'Alessandro, D. ELSEVIER SCIENCE INC. 2023: S185

  View details for Web of Science ID 000992480600384

• Outcomes in Children and Young Adults with Congenital Heart Disease Undergoing Transplant: A Subgroup Analysis of the Guardian Heart Registry Boston, U., Zuckermann, A., Stukov, Y., Schroder, J., Shudo, Y., Bustamante-Munguira, J., Leacche, M., Silvestry, S., Kawabori, M., Takeda, K., Jacobs, J. P. ELSEVIER SCIENCE INC. 2023: S268

  View details for Web of Science ID 000992480600590

• Revised Heart Allocation Policy Improved Waitlist Mortality and Waiting Time With Maintained Outcomes in En-Bloc Heart-Lung Transplant Candidates and Recipients. Transplant international : official journal of the European Society for Organ Transplantation Shudo, Y., He, H., Elde, S., Woo, Y. J. 2023; 36: 11956

  Abstract

  The revised United Network for Organ Sharing heart allocation policy was implemented in October 2018. Using a national transplant database, this study evaluated the transplant rate, waitlist mortality, waiting time, and other outcomes of en-bloc heart-lung transplantation recipients. Adult patients registered on the national database for heart-lung transplants before and after the policy update were selected as cohorts. Baseline characteristics, transplant rates, waitlist mortality, waiting times, and other outcomes were compared between the two periods. In total, 370 patients were registered for heart-lung transplants during the pre- and post-periods. There were significantly higher transplant rates, shorter waitlist times, and substantially reduced waitlist mortality in the post-period. Registered patients waitlisted in the post-period had significantly higher utilization of intra-aortic balloon pumps, extracorporeal membrane oxygenation, and overall life support, including ventricular assist devices. Transplant recipients had significantly longer ischemic times, increased transport distances, and shorter waiting times before transplantation in the post-policy period. Transplant recipients held similar short-term survival before and after the policy change (log-rank test, p = 0.4357). Therefore, the revised policy significantly improved access to en-bloc heart-lung allografts compared with the prior policy, with better waitlist outcomes and similar post-transplant outcomes.

  View details for DOI 10.3389/ti.2023.11956

  View details for PubMedID 38152546

• IMPACT OF C-REACTIVE PROTEIN ON ANTICOAGULATION MONITORING IN EXTRACORPOREAL MEMBRANE OXYGENATION Madhok, J., ODonnell, C., Jin, J., Owyang, C., Weimer, J., Pashun, R., Shudo, Y., McNulty, J., Chadwick, B., Ruoss, S., Rao, V., Zehnder, J., Hsu, J. LIPPINCOTT WILLIAMS & WILKINS. 2023: 54

  View details for Web of Science ID 000921450900108

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

  Abstract

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

  View details for DOI 10.1097/TP.0000000000004416

  View details for PubMedID 36510359

• Multicenter Registry Using Propensity Score Analysis to Compare a Novel Transport/Preservation System to Traditional Means on Postoperative Hospital Outcomes and Costs for Heart Transplant Patients. ASAIO journal (American Society for Artificial Internal Organs : 1992) Voigt, J. D., Leacche, M., Copeland, H., Wolfe, S. B., Pham, S. M., Shudo, Y., Molina, E., Jacobs, J. P., Stukov, Y., Meyer, D., Philpott, J., Kawabori, M., Schroder, J., Silvestry, S., D'Alessandro, D. 2022

  Abstract

  The standard method for cardiac allograft preservation for the past 50 years has been static storage using crushed ice. A heart transplant transportation system designed to improve preservation quality with temperature monitoring, the Paragonix SherpaPak Cardiac Transport System (SCTS), was evaluated for its impact on postoperative costs relative to conventional ice storage. Observational US multicenter registry data collected during the August 2015 to November 2021 timeframe from 12 transplant hospitals were analyzed using logistic regression analysis and propensity matching to balance measured baseline covariates and to reduce selection bias. Hospital cost and outcome data post-transplant were then evaluated using various statistical methods. One hundred seventy-four (174) patients were identified resulting in 87 matches. Baseline characteristics were similar between groups. The SCTS group had a significantly lower proportion of ICU days on post-transplant mechanical circulatory support (p < 0.0001); significantly fewer patients on extracorporeal membrane oxygenation (p = 0.017); and significantly fewer patients experiencing severe primary graft dysfunction (PGD) (p = 0.03). Overall hospital plus mechanical circulatory support post-transplant costs were significantly lower by $26.7K in the CTS cohort (p = 0.03). Use of the SCTS is associated with improved clinical outcomes resulting in significantly lower overall hospital care costs.

  View details for DOI 10.1097/MAT.0000000000001844

  View details for PubMedID 36399786

• Angiogenic stem cell delivery platform to augment post-infarction neovasculature and reverse ventricular remodeling. Scientific reports Shin, H. S., Thakore, A., Tada, Y., Pedroza, A. J., Ikeda, G., Chen, I. Y., Chan, D., Jaatinen, K. J., Yajima, S., Pfrender, E. M., Kawamura, M., Yang, P. C., Wu, J. C., Appel, E. A., Fischbein, M. P., Woo, Y., Shudo, Y. 2022; 12 (1): 17605

  Abstract

  Many cell-based therapies are challenged by the poor localization of introduced cells and the use of biomaterial scaffolds with questionable biocompatibility or bio-functionality. Endothelial progenitor cells (EPCs), a popular cell type used in cell-based therapies due to their robust angiogenic potential, are limited in their therapeutic capacity to develop into mature vasculature. Here, we demonstrate a joint delivery of human-derived endothelial progenitor cells (EPC) and smooth muscle cells (SMC) as a scaffold-free, bi-level cell sheet platform to improve ventricular remodeling and function in an athymic rat model of myocardial infarction. The transplanted bi-level cell sheet on the ischemic heart provides a biomimetic microenvironment and improved cell-cell communication, enhancing cell engraftment and angiogenesis, thereby improving ventricular remodeling. Notably, the increased density of vessel-like structures and upregulation of biological adhesion and vasculature developmental genes, such as Cxcl12 and Notch3, particularly in the ischemic border zone myocardium, were observed following cell sheet transplantation. We provide compelling evidence that this SMC-EPC bi-level cell sheet construct can be a promising therapy to repair ischemic cardiomyopathy.

  View details for DOI 10.1038/s41598-022-21510-y

  View details for PubMedID 36266453

  View details for PubMedCentralID PMC9584918

• A value-based approach to optimize red blood cell transfusion in patients receiving extracorporeal membrane oxygenation. Perfusion Shudo, Y., Cheng, N., He, H., Rosenberg, C., Hiesinger, W., Hadhazy, E., Shepard, J., Krishna, P., Resnik, J., Fong, R., Hill, C., Hsu, J. L., Maggio, P. M., Chang, S., Boyd, J. H., Woo, Y. J. 2022: 2676591221128138

  Abstract

  INTRODUCTION: The risk, cost, and adverse outcomes associated with packed red blood cell (RBC) transfusions in patients with cardiopulmonary failure requiring extracorporeal membrane oxygenation (ECMO) have raised concerns regarding the overutilization of RBC products. It is, therefore, necessary to establish optimal transfusion criteria and protocols for patients supported with ECMO. The goal of this study was to establish specific criteria for RBC transfusions in patients undergoing ECMO.METHODS: This was a retrospective cohort study conducted at Stanford University Hospital. Data on RBC utilization during the entire hospital stay were obtained, which included patients aged ≥18years who received ECMO support between 1 January 2017, and 30 June 2020 (n = 281). The primary outcome was in-hospital mortality.RESULTS: Hemoglobin (HGB) levels >10g/dL before transfusion did not improve in-hospital survival. Therefore, we revised the HGB threshold to ≤10g/dL to guide transfusion in patients undergoing ECMO. To validate this intervention, we prospectively compared the pre- and post-intervention cohorts for in-hospital mortality. Post-intervention analyses found 100% compliance for all eligible records and a decrease in the requirement for RBC transfusion by 1.2 units per patient without affecting the mortality.CONCLUSIONS: As an institution-driven value-based approach to guide transfusion in patients undergoing ECMO, we lowered the threshold HGB level. Validation of this revised intervention demonstrated excellent compliance and reduced the need for RBC transfusion while maintaining the clinical outcome. Our findings can help reform value-based healthcare in this cohort while maintaining the outcome.

  View details for DOI 10.1177/02676591221128138

  View details for PubMedID 36148806

• Combined Heart-Lung Transplantation Outcomes in Asian Populations: National Database Analysis. JACC. Asia Shudo, Y., Leipzig, M., He, H., Ingle, S. M., Bhatt, R. H., Shin, H., Woo, Y. J. 2022; 2 (4): 504-512

  Abstract

  Background: Heart-lung transplantation (HLTx) is a definitive surgical procedure for end-stage cardiopulmonary failure. Studies to understand the relationship between ethnicity and race and outcomes after HLTx are needed to uphold equitable HLTx access to the increasingly diverse U.S. population facing advanced cardiopulmonary failure.Objectives: This study sought to examine the outcomes of HLTx recipients of Asian origin, with emphasis on the ethnic and racial disparities in the outcomes.Methods: We analyzed data from the United Network for Organ Sharing (UNOS) for patients of≥18 years of age who underwent HLTx between 1987 and 2021. Propensity-score matching was performed between Asian and non-Hispanic Whites (NHWs), with a 1:3 matching ratio based on the propensity score of each patient estimated by multivariable logistic regression.Results: We identified 42 Asian and Asian American heart-lung transplant recipients and 834 NHW recipients. In the pre-matched cohort, the median survival was 1,459days (IQR: 1,080-2,692days) in Asian recipients after transplantation, whereas it was 1,521days (IQR: 1,262-1,841days) in White recipients. Of the 876 recipients, 156 transplants were successfully matched (Asian, n=36; NHW, n=108). Among the post-transplantation outcomes, there were no significant differences in morbidity and mortality between Asian and NHW cohorts.Conclusions: This large-scale analysis in Asian patients will have important implications in Asian countries that have relatively fewer HLTx surgeries. An outcome equivalent to NHW in Asian patients, as demonstrated in our study, could be the driving force for further expansion of HLTx surgeries in Asian countries.

  View details for DOI 10.1016/j.jacasi.2022.03.012

  View details for PubMedID 36339364

• Combining donor derived cell free DNA and gene expression profiling for non-invasive surveillance after heart transplantation. Clinical transplantation Henricksen, E. J., Moayedi, Y., Purewal, S., Twiggs, J. V., Waddell, K., Luikart, H., Han, J., Feng, K., Wayda, B., Lee, R., Shudo, Y., Jimenez, S., Khush, K. K., Teuteberg, J. J. 2022: e14699

  Abstract

  BACKGROUND: Donor-derived cell free DNA (dd-cfDNA) and gene expression profiling (GEP) offer non-invasive alternatives to rejection surveillance after heart transplantation, however there is little evidence on the paired use of GEP and dd-cfDNA for rejection surveillance.METHODS: A single center, retrospective analysis of adult heart transplant recipients. A GEP cohort, transplanted from January 1, 2015 through December 31, 2017 and eligible for rejection surveillance with GEP was compared to a paired testing cohort, transplanted July 1, 2018 through June 30, 2020, with surveillance from both dd-cfDNA and GEP. The primary outcomes were survival and rejection-free survival at one year post-transplant.RESULTS: In total 159 patients were included, 95 in the GEP and 64 in the paired testing group. There were no differences in baseline characteristics, except for less use of induction in the paired testing group (65.6%) compared to the GEP group (98.9%), p< 0.01. At one-year, there were no differences between the paired testing and GEP groups in survival (98.4% v. 94.7%, p = 0.23) or rejection-free survival (81.3% v. 73.7% p = 0.28).CONCLUSIONS: Compared to post-transplant rejection surveillance with GEP alone, pairing dd-cfDNA and GEP testing was associated with similar survival and rejection-free survival at one year while requiring significantly fewer biopsies. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/ctr.14699

  View details for PubMedID 35559582

• Exvivo aortic valve replacement before orthotopic heart transplantation. JTCVS techniques Elde, S. F., Guenthart, B. A., Shudo, Y., Woo, Y. J. 2022; 12: 118-120

  View details for DOI 10.1016/j.xjtc.2022.01.008

  View details for PubMedID 35403016

• Keep Your Cool! One Year Outcomes with Use of a Hypothermic Preservation System Compared to Standard Storage with Ice During Heart Procurement Teuteberg, J., Henricksen, E., Khush, K., Kim, D. T., Moayedi, Y., Luikart, H., Wainwright, R., Woo, J. Y., Hiesinger, W., Koyano, T., Shudo, Y. ELSEVIER SCIENCE INC. 2022: S201

  View details for Web of Science ID 000780119700452

• Expanding Heart Transplants from Donors After Circulatory Death (DCD) - Results of the First Randomized Controlled Trial Using the Organ Care System (OCS (TM)) Heart - (OCS DCD Heart Trial) Schroder, J. N., Shah, A., Pretorius, V., Smith, J., Daneshmand, M., Geirsson, A., Pham, S., Um, J., Silvestry, S., Shaffer, A., Mudy, K., Kai, M., Joyce, D., Philpott, J., Takeda, K., Goldstein, D., Shudo, Y., Couper, G., Mallidi, H., Esmailian, F., Pham, D., Salerno, C., Lozonschi, L., Quader, M., Patel, C., DeVore, A., Bryner, B., Madsen, J., Absi, T., Milano, C., D'Alessandro, D. ELSEVIER SCIENCE INC. 2022: S72

  View details for Web of Science ID 000780119700145

• Predicting Survival in Combined Heart-Liver Transplantation Compared to Heart Transplantation Alone Currie, M. E., Rinewalt, D. E., Leipzig, M., Shudo, Y., Kaghazchi, A., Zhu, Y., Woo, Y. J. ELSEVIER SCIENCE INC. 2022: S84-S85

  View details for Web of Science ID 000780119700173

• Outcomes of Patients Undergoing Combined Heart-Kidney Transplantation with or without Prior Ventricular Assist Device Currie, M. E., Leipzig, M., Kaghazchi, A., Shudo, Y., Woo, Y. J. ELSEVIER SCIENCE INC. 2022: S85-S86

  View details for Web of Science ID 000780119700176

• Increasing Utilization of Extended Criteria Donor After Brain Death (DBD) Hearts Seldomly Used for Transplantation in the US Due to Limitation of Ischemic Cold Storage-2-Year Results of the OCS Heart EXPAND Prospective Multi-Center Trial (OCS Heart EXPAND) Schroder, N., Shah, A., Anyanwu, A., D'Alessandro, D., Streuber, M., Mudy, K., Shudo, Y., Esmailian, F., Liao, K., Pagani, F., Silvestry, S., Wang, I., Gananpathi, A., Salerno, C., Patel, C., DeVore, A., Koomalsingh, K., Absi, T., Khaghani, A., Milano, C., Smith., J. W. ELSEVIER SCIENCE INC. 2022: S73

  View details for Web of Science ID 000780119700147

• Second Report of the GUARDIAN Registry: An International Consortium Examining the Effect of Controlled Hypothermic Preservation in Heart Transplantation Zuckermann, A., Leacche, M., Philpott, J., Pham, S., Shudo, Y., Bustamante-Munguira, J., Jacobs, J., Silvestry, S., Schroder, J., Eixeres-Esteve, A., Molina, E., Meyer, D., Kawabori, M., D'Alessandro, D. ELSEVIER SCIENCE INC. 2022: S477

  View details for Web of Science ID 000780119701434

• US Multi-Center Analysis of the Global Utilization and Registry Database for Improved Heart Preservation (GUARDIAN) Registry: 1-Year Transplant Survival Analysis Leacche, M., Philpott, J., Pham, S., Shudo, Y., Kawabori, M., Jacobs, J., Silvestry, S., Schroder, J., Molina, E., Meyer, D., D'Alessandro., D. ELSEVIER SCIENCE INC. 2022: S30-S31

  View details for Web of Science ID 000780119700048

• 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

  Abstract

  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

• 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

  Abstract

  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

• Extended Static Hypothermic Preservation In Cardiac Transplantation: A Case Report. Transplantation proceedings Guenthart, B. A., Krishnan, A., Koyano, T., La Francessca, S., Chan, J., Alassar, A., Macarthur, J. W., Shudo, Y., Hiesinger, W., Woo, Y. J. 2021

  Abstract

  BACKGROUND: The donor shortage poses a major limitation to use of heart transplantation. Novel strategies such as use of expanded-criteria donors with prolonged ischemia times are being employed to address this need. Recent developments in static hypothermia have allowed for the safe use of cardiac allografts with prolonged ischemic times.CASE REPORT: We present the case of a 68-year-old woman with valvular cardiomyopathy refractory to medical therapy who underwent orthotopic heart transplantation with a cardiac allograft exposed to elevated ischemic times. This was achieved through use of the federally approved SherpaPak Cardiac Transport System for transportation of the allograft. This method of static hypothermic organ preservation allowed for a 330-minute total ischemic time, including 283 minutes of storage within the preservation system. The patient tolerated the procedure well and was discharged on postoperative day 10, with excellent graft function and no evidence of rejection 3 months postoperatively.CONCLUSIONS: Though traditionally ischemic times of 240 minutes or less are recommended for cardiac allografts, we demonstrate, to our knowledge, the longest reported ischemic time of 330 minutes via use of a novel method of static hypothermia for organ preservation. The recipient had an excellent outcome postoperatively, demonstrating the potential for this new organ preservation system to expand the donor pool and improve access and use of heart transplantation.

  View details for DOI 10.1016/j.transproceed.2021.08.021

  View details for PubMedID 34521542

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

  Abstract

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

  View details for DOI 10.1093/eurheartj/ehab416

  View details for PubMedID 34333595

• Patient-Specific Computational Fluid Dynamics Reveal Localized Flow Patterns Predictive of Post-Left Ventricular Assist Device Aortic Incompetence. Circulation. Heart failure Shad, R., Kaiser, A. D., Kong, S., Fong, R., Quach, N., Bowles, C., Kasinpila, P., Shudo, Y., Teuteberg, J., Woo, Y. J., Marsden, A. L., Hiesinger, W. 2021: CIRCHEARTFAILURE120008034

  Abstract

  BACKGROUND: Progressive aortic valve disease has remained a persistent cause of concern in patients with left ventricular assist devices. Aortic incompetence (AI) is a known predictor of both mortality and readmissions in this patient population and remains a challenging clinical problem.METHODS: Ten left ventricular assist device patients with de novo aortic regurgitation and 19 control left ventricular assist device patients were identified. Three-dimensional models of patients' aortas were created from their computed tomography scans, following which large-scale patient-specific computational fluid dynamics simulations were performed with physiologically accurate boundary conditions using the SimVascular flow solver.RESULTS: The spatial distributions of time-averaged wall shear stress and oscillatory shear index show no significant differences in the aortic root in patients with and without AI (mean difference, 0.67 dyne/cm2 [95% CI, -0.51 to 1.85]; P=0.23). Oscillatory shear index was also not significantly different between both groups of patients (mean difference, 0.03 [95% CI, -0.07 to 0.019]; P=0.22). The localized wall shear stress on the leaflet tips was significantly higher in the AI group than the non-AI group (1.62 versus 1.35 dyne/cm2; mean difference [95% CI, 0.15-0.39]; P<0.001), whereas oscillatory shear index was not significantly different between both groups (95% CI, -0.009 to 0.001; P=0.17).CONCLUSIONS: Computational fluid dynamics serves a unique role in studying the hemodynamic features in left ventricular assist device patients where 4-dimensional magnetic resonance imaging remains unfeasible. Contrary to the widely accepted notions of highly disturbed flow, in this study, we demonstrate that the aortic root is a region of relatively stagnant flow. We further identified localized hemodynamic features in the aortic root that challenge our understanding of how AI develops in this patient population.

  View details for DOI 10.1161/CIRCHEARTFAILURE.120.008034

  View details for PubMedID 34139862

• Extracorporeal Membrane Oxygenation Bridge to Heart-Lung Transplantation. ASAIO journal (American Society for Artificial Internal Organs : 1992) Shudo, Y., Elde, S., Lingala, B., He, H., Casselman, K. G., Zhu, Y., Kasinpila, P., Woo, Y. J. 2021

  View details for DOI 10.1097/MAT.0000000000001457

  View details for PubMedID 34843181

• Long-term survival in patients with post-LVAD right ventricular failure: multi-state modelling with competing outcomes of heart transplant. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Shad, R., Fong, R., Quach, N., Bowles, C., Kasinpila, P., Li, M., Callon, K., Castro, M., Guha, A., Suarez, E. E., Lee, S., Jovinge, S., Boeve, T., Shudo, Y., Langlotz, C. P., Teuteberg, J., Hiesinger, W. 2021

  Abstract

  BACKGROUND: Multicenter data on long term survival following LVAD implantation that make use of contemporary definitions of RV failure are limited. Furthermore, traditional survival analyses censor patients who receive a bridge to heart transplant. Here we compare the outcomes of LVAD patients who develop post-operative RV failure accounting for the transitional probability of receiving an interim heart transplantation.METHODS: We use a retrospective cohort of LVAD patients sourced from multiple high-volume centers based in the United States. Five- and ten-year survival accounting for transition probabilities of receiving a heart transplant were calculated using a multi-state Aalen Johansen survival model.RESULTS: Of the 897 patients included in the study, 238 (26.5%) developed post-operative RV failure at index hospitalization. At 10 years the probability of death with post-op RV failure was 79.28% vs 61.70% in patients without (HR 2.10; 95% CI 1.72 - 2.57; p=< .001). Though not significant, patients with RV failure were less likely to be bridged to a heart transplant (HR 0.87, p=.4). Once transplanted the risk of death between both patient groups remained equivalent; the probability of death after a heart transplant was 3.97% in those with post-operative RV failure shortly after index LVAD implant, as compared to 14.71% in those without.CONCLUSIONS AND RELEVANCE: Long-term durable mechanical circulatory support is associated with significantly higher mortality in patients who develop post-operative RV failure. Improving outcomes may necessitate expeditious bridge to heart transplant wherever appropriate, along with critical reassessment of organ allocation policies.

  View details for DOI 10.1016/j.healun.2021.05.002

  View details for PubMedID 34167863

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

  Abstract

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

  View details for DOI 10.1016/j.healun.2021.04.016

  View details for PubMedID 34083118

• Combining Donor Derived Cell-Free DNA and Gene Expression Profiling for Non-Invasive Surveillance after Heart Transplantation Henricksen, E. J., Purewal, S., Moayedi, Y., Waddell, K., Gordon, J., Morales, P., Luikart, H., Han, J., Feng, K. Y., Lee, R., Shudo, Y., Jimenez, S., Khush, K. K., Teuteberg, J. J. ELSEVIER SCIENCE INC. 2021: S43

  View details for Web of Science ID 000631254400079

• Longest Storage Period with Static Hypothermic Preservation in Cardiac Transplantation: Initial Experience in the West Coast Guenthart, B. A., Alassar, A., Koyano, T., La Francesca, S., Chan, J. L., Krishnan, A., MacArthur, J. W., Shudo, Y., Hiesinger, W., Woo, Y. ELSEVIER SCIENCE INC. 2021: S471

  View details for Web of Science ID 000631254401420

• Racial Disparities in Advanced Heart Failure Therapies: Are Outcomes the Correct Metric? Bowles, C., Shad, R., Fong, R., Quach, N., Kasinpila, P., Lingala, B., Zhu, Y., MacArthur, J. W., Shudo, Y., Hiesinger, W. ELSEVIER SCIENCE INC. 2021: S272

  View details for Web of Science ID 000631254400647

• First lung and kidney multi-organ transplant following COVID-19 Infection. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Guenthart, B. A., Krishnan, A., Alassar, A., Madhok, J., Kakol, M., Miller, S., Cole, S. P., Rao, V. K., Acero, N. M., Hill, C. C., Cheung, C., Jackson, E. C., Feinstein, I., Tsai, A. H., Mooney, J. J., Pham, T., Elliott, I. A., Liou, D. Z., La Francesca, S., Shudo, Y., Hiesinger, W., MacArthur, J. W., Brar, N., Berry, G. J., McCarra, M. B., Desai, T. J., Dhillon, G. S., Woo, Y. J. 2021

  Abstract

  As the world responds to the global crisis of the COVID-19 pandemic an increasing number of patients are experiencing increased morbidity as a result of multi-organ involvement. Of these, a small proportion will progress to end-stage lung disease, become dialysis dependent, or both. Herein, we describe the first reported case of a successful combined lung and kidney transplantation in a patient with COVID-19. Lung transplantation, isolated or combined with other organs, is feasible and should be considered for select patients impacted by this deadly disease.

  View details for DOI 10.1016/j.healun.2021.02.015

  View details for PubMedID 34059432

• Current Status and Limitations of Myocardial Infarction Large Animal Models in Cardiovascular Translational Research. Frontiers in bioengineering and biotechnology Shin, H. S., Shin, H. H., Shudo, Y. 2021; 9: 673683

  Abstract

  Establishing an appropriate disease model that mimics the complexities of human cardiovascular disease is critical for evaluating the clinical efficacy and translation success. The multifaceted and complex nature of human ischemic heart disease is difficult to recapitulate in animal models. This difficulty is often compounded by the methodological biases introduced in animal studies. Considerable variations across animal species, modifications made in surgical procedures, and inadequate randomization, sample size calculation, blinding, and heterogeneity of animal models used often produce preclinical cardiovascular research that looks promising but is irreproducible and not translatable. Moreover, many published papers are not transparent enough for other investigators to verify the feasibility of the studies and the therapeutics' efficacy. Unfortunately, successful translation of these innovative therapies in such a closed and biased research is difficult. This review discusses some challenges in current preclinical myocardial infarction research, focusing on the following three major inhibitors for its successful translation: Inappropriate disease model, frequent modifications to surgical procedures, and insufficient reporting transparency.

  View details for DOI 10.3389/fbioe.2021.673683

  View details for PubMedID 33996785

• Predicting post-operative right ventricular failure using video-based deep learning. Nature communications Shad, R., Quach, N., Fong, R., Kasinpila, P., Bowles, C., Castro, M., Guha, A., Suarez, E. E., Jovinge, S., Lee, S., Boeve, T., Amsallem, M., Tang, X., Haddad, F., Shudo, Y., Woo, Y. J., Teuteberg, J., Cunningham, J. P., Langlotz, C. P., Hiesinger, W. 2021; 12 (1): 5192

  Abstract

  Despite progressive improvements over the decades, the rich temporally resolved data in an echocardiogram remain underutilized. Human assessments reduce the complex patterns of cardiac wall motion, to a small list of measurements of heart function. All modern echocardiography artificial intelligence (AI) systems are similarly limited by design - automating measurements of the same reductionist metrics rather than utilizing the embedded wealth of data. This underutilization is most evident where clinical decision making is guided by subjective assessments of disease acuity. Predicting the likelihood of developing post-operative right ventricular failure (RV failure) in the setting of mechanical circulatory support is one such example. Here we describe a video AI system trained to predict post-operative RV failure using the full spatiotemporal density of information in pre-operative echocardiography. We achieve an AUC of 0.729, and show that this ML system significantly outperforms a team of human experts at the same task on independent evaluation.

  View details for DOI 10.1038/s41467-021-25503-9

  View details for PubMedID 34465780

• Operative Technique of Donor Organ Procurement for En Bloc Heart-Liver Transplantation. Transplantation Elde, S. n., Brubaker, A. L., Than, P. A., Rinewalt, D. n., MacArthur, J. W., Alassar, A. n., Bonham, C. A., Esquivel, C. O., Shudo, Y. n., Concepcion, W. n., Woo, Y. J. 2021

  Abstract

  Combined heart-liver transplant is an emerging option for patients with indications for heart transplantation and otherwise prohibitive hepatic dysfunction. Heart-liver transplantation is particularly relevant for patients with single ventricle physiology who often develop Fontan-associated liver disease and fibrosis. While only performed at a limited number of centers, several approaches to combined heart-liver transplantation have been described. The en bloc technique offers several potential advantages over the traditional sequential technique. Specifically, en bloc heart-liver transplantation may allow improved hemodynamics, decreased bleeding, reduced liver allograft ischemic time, and may result in reduced rates of graft dysfunction. Here we describe our center's en bloc heart-liver procurement technique in detail, with the aim of allowing broader use and standardization of this technique. Supplemental Visual Abstract; http://links.lww.com/TP/C147.

  View details for DOI 10.1097/TP.0000000000003697

  View details for PubMedID 33606485

• Donors after circulatory death heart trial. Future cardiology Shudo, Y., Benjamin-Addy, R., Koyano, T. K., Hiesinger, W., MacArthur, J. W., Woo, Y. J. 2020

  Abstract

  Orthotopic heart transplantation is the gold standard treatment for end-stage heart failure. However, the persistent shortage of available donor organs has resulted in an ever-increasing waitlist and longer waiting periods for transplantation. On the contrary, increasing the number of heart transplants by preserving extended criteria donors and donation after circulatory deathhearts with the Organ Care System (OCS) Heart System has the potential to provide the goldstandard, life-saving treatment to patients with end-stage heart failure. The objective of the Donation After Circulatory Death Heart Trial is to evaluate the effectiveness of the OCS Heart System to preserve and assess hearts donated after circulatory death for transplantation to increase the pool of donor hearts available for transplantation, which can potentially provide patients with end-stage heart failure with the life-saving treatment. Clinical Trial Registration: NCT03831048 (ClinicalTrials.gov).

  View details for DOI 10.2217/fca-2020-0070

  View details for PubMedID 32628044

• Relation of Length of Survival After Orthotopic Heart Transplantation to Age of the Donor. The American journal of cardiology Shudo, Y., Guenther, S. P., Lingala, B., He, H., Hiesinger, W., MacArthur, J. W., Currie, M. E., Lee, A. M., Boyd, J. H., Woo, Y. J. 2020

  Abstract

  We aim to evaluate the impact of donor age on the outcomes in orthotropic heart transplantation recipients. The United Network for Organ Sharing database was queried for adult patients (age; ≥60) underwent first-time orthotropic heart transplantation between 1987 and 2019 (n = 18,447). We stratified the cohort by donor age; 1,702 patients (9.2%) received a heart from a donor age of <17 years; 11,307 patients (61.3%) from a donor age of 17 ≥, < 40; 3,525 patients (19.1%) from a donor age of 40 ≥, < 50); and 1,913 patients (10.4%) from a donor age of ≥50. There was a significant difference in the survival likelihood (p < 0.0001) based on donor's age-based categorized cohort, however, the median survival was 10.5 years in the cohort in whom the donor was <17, 10.3 years in whom the donor was 17 ≥, < 40, 9.4 years in whom the donor was 40 ≥, < 50, and 9.0 years in whom the donor was ≥ 50. Additionally, there was no significant difference in the episode of acute rejection (p = 0.19) nor primary graft failure (p = 0.24). In conclusion, this study demonstrated that patients receiving hearts from the donor age of ≥50 years old showed slight inferior survival likelihood, but appeared to be equivalent median survival.

  View details for DOI 10.1016/j.amjcard.2020.06.036

  View details for PubMedID 32736794

• Cardiac transplantation for cancer involving the heart. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Wingo, M., de Biasi, A. R., Shudo, Y., Bharathi, V., Blackburn, A., Gaudino, M., Girardi, L. N., Woo, Y. J. 2020

  View details for DOI 10.1016/j.healun.2020.05.010

  View details for PubMedID 32532569

• The Impact of Donor Gender on Heart Transplantation Outcomes - A Study of over 60,000 Patients in the United States Zhu, Y., Shudo, Y., Lingala, B., Elde, S., Woo, Y. ELSEVIER SCIENCE INC. 2020: S42

  View details for Web of Science ID 000522637200081

• Are Two Tests Better Than One? Combining Donor Derived Cell-Free DNA and Gene Expression Profiling for Non-Invasive Surveillance after Heart Transplantation Purewal, S., Moayedi, Y., Runeckles, K., Fan, C., Gordon, J., Henricksen, E. J., Oro, G., Shudo, Y., Khush, K. K., Teuteberg, J. ELSEVIER SCIENCE INC. 2020: S71

  View details for Web of Science ID 000522637200152

• Cardiac Transplantation for Cancer Involving the Heart: Results from 35 Years of Transplants from the ISHLT Registry Wingo, M., de Biasi, A. R., Shudo, Y., Lingala, B., Gaudino, M., Girardi, L. N., Woo, Y. J. ELSEVIER SCIENCE INC. 2020: S126

  View details for Web of Science ID 000522637200288

• A Decade of Single Center HeartWare (TM) HVAD (TM) Experience Guenther, S. P., Fong, R., Abovwe, N., Shad, R., MacArthur, J. W., Teuteberg, J., Woo, Y., Shudo, Y., Hiesinger, W. ELSEVIER SCIENCE INC. 2020: S339

  View details for Web of Science ID 000522637202190

• Commentary: Accepting only over-sized donors for adult congenital heart disease-Is it being overcautious? The Journal of thoracic and cardiovascular surgery Shudo, Y., Maeda, K. 2020

  View details for DOI 10.1016/j.jtcvs.2020.03.029

  View details for PubMedID 32279963

• Impact of Surgical Approach in Double Lung Transplantation: Median Sternotomy vs Clamshell Thoracotomy. Transplantation proceedings Shudo, Y. n., Rinewalt, D. n., Lingala, B. n., Kim, F. Y., He, H. n., Boyd, J. H., Lee, A. M., Hiesinger, W. n., Currie, M. E., MacArthur, J. W., Woo, Y. J. 2020

  Abstract

  Double lung transplantation (DLT) remains the gold standard for end-stage lung disease. Although DLT was historically performed via clamshell thoracotomy, recently the median sternotomy has emerged as a viable alternative. As the ideal surgical approach remains unclear, the aim of our study was to compare the short- and long-term outcomes of these 2 surgical approaches in DLT.We retrospectively reviewed 192 consecutive adult patients who underwent primary DLT at our institution between 2012 and 2017 (sternotomy, n = 147; clamshell, n = 45). The impact of each surgical approach on post-transplant morbidity was investigated, and the overall survival probability analyses were performed.There were no significant differences in recipients' baseline and donors' characteristics and bilateral allograft ischemic time. Freedom from primary graft dysfunction, acute rejection episodes, postoperative prolonged ventilator support, tracheostomy, postoperative stroke, and airway dehiscence were comparable between these 2 groups. The duration of cardiopulmonary bypass and operative time were significantly longer in the clamshell thoracotomy group. Postoperative extracorporeal membrane oxygenation usage tended to be more frequent in the clamshell thoracotomy group than the median sternotomy group, despite no statistical significance. Length of hospital and intensive care unit stay were not influenced by the type of incision. There was no significant difference in overall survival between these 2 procedure groups (P = .61, log-rank test).The median sternotomy approach in DLT decreases operative time and more importantly leads to a shorter duration of cardiopulmonary bypass. The type of surgical approach did not show any statistically significant impact on adult DLT recipients' morbidity and survival.

  View details for DOI 10.1016/j.transproceed.2019.10.018

  View details for PubMedID 31911057

• Operative Techniques and Pitfalls in Donor Bilateral Lung Procurement. Transplantation proceedings Dalal, A. R., Rinewalt, D. E., MacArthur, J. W., Shudo, Y. n., Woo, Y. J. 2020

  Abstract

  Demand for lung transplant continues to grow nationally, and the number of donation after brain death and donation after circulatory death lung procurements increases each year.We describe the Stanford technique for bilateral lung procurement for donation after brain death and donation after circulatory death and highlight the pitfalls and common mistakes to standardize the procurement process and ensure proper harvesting to prevent organ loss.Damage to the lung graft during bilateral en bloc procurement most commonly results from either poor preservation or injury to a pulmonary vein during division of the left atrial cuff.En bloc bilateral lung procurement should be standardized to ensure reproducible graft harvesting and preservation while teaching new generations of transplant surgeons.

  View details for DOI 10.1016/j.transproceed.2020.01.023

  View details for PubMedID 32139275

• 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)

  Abstract

  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

• 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

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

  Abstract

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

  View details for DOI 10.1016/j.jtcvs.2020.06.121

  View details for PubMedID 32798029

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

  Abstract

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

  View details for DOI 10.12659/AOT.922723

  View details for PubMedID 32527989

• 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)

  Abstract

  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

• Three-Dimensional Multi-layered Microstructure using Laser Direct-Writing System. Tissue engineering. Part A Shudo, Y. n., MacArthur, J. W., Kunitomi, Y. n., Joubert, L. M., Kawamura, M. n., Ono, J. n., Thakore, A. D., Jaatinen, K. J., Eskandari, A. n., Hironaka, C. E., Shin, H. S., Woo, Y. J. 2020

  Abstract

  Tissue engineering is an essential component of developing effective regenerative therapies. Here, we introduce a promising method to create scaffold-free three dimensional (3D) tissue engineered multi-layered microstructures from cultured cells using the "3D tissue fabrication system" (Regenova®, Cyfuse, Japan). This technique utilizes the adhesive nature of cells. When cells are cultured in non-adhesive wells, they tend to aggregateand form a spheroidal structure. The advantage of this approach is that cellular components can be mixed into one spheroid, thereby promoting the formation of extracellular matrices, such as collagen and elastin. This system enables one to create a pre-designed 3D structure composed of cultured cells. We found the advantages of this system to be: (1) the length, size, and shape of the structure were designable and highly reproducible because of the computer controlled robotics system, (2) the graftable structure could be created within a reasonable period (8 days), and (3) the constructed tissue did not contain any foreign material, which may avoid the potential issues ofcontamination, biotoxicity, and allergy. The utilization of this robotic system enabled thecreation of a 3D multi-layered microstructure made of cell based spheres with a satisfactory mechanical properties and abundant extracellular matrix during a short period of time. These results suggest that this new technology will represent a promising, attractive, and practical strategy in the field of tissue engineering.

  View details for DOI 10.1089/ten.TEA.2019.0313

  View details for PubMedID 32085692

• Multidisciplinary approach utilizing early, intensive physical rehabilitation to accelerate recovery from veno-venous extracorporeal membrane oxygenation EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Zhu, Y., Bankar, D., Shudo, Y., Woo, Y. 2019; 56 (4): 811–12

  View details for DOI 10.1093/ejcts/ezz042

  View details for Web of Science ID 000491248300025

• 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

• Cardioaortic replacement for a ruptured root pseudoaneurysm with pulsatile subcutaneous extension EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Wang, H., Shudo, Y., Hittinger, S. A., Woo, Y. 2019; 56 (3): 615–17

  View details for DOI 10.1093/ejcts/ezy447

  View details for Web of Science ID 000493091000028

• A modified implantation technique for temporary right ventricular assist device: Enabling ambulation and less invasive decannulation. Journal of cardiac surgery Rinewalt, D., Shudo, Y., MacArthur, J. W., Woo, Y. J., Hiesinger, W. 2019

  Abstract

  This report describes our unique temporary right ventricular assist device (RVAD) implantation technique, which enables early mobilization even during biventricular support and subsequent less invasive RVAD removal without needing resternotomy upon recovery.

  View details for DOI 10.1111/jocs.14193

  View details for PubMedID 31389624

• Comprehensive Analysis of Differential Expressed Genes Related with Myocardial Reverse Remodeling Following HeartWare Ventricular Assist Device Implantation Shudo, Y., Jaatinen, K. J., NIshiga, M., Chen, I. Y., Greene, C. L., Koyano, T. K., Fong, R. W., Boyd, J. H., Lee, A. M., Hiesinger, W., Woo, J. ELSEVIER SCIENCE INC. 2019: S244

  View details for DOI 10.1016/j.healun.2019.01.603

  View details for Web of Science ID 000461365101285

• Comparison of Patients Undergoing Multiorgan Transplantation with or without Prior Ventricular Assist Device Currie, M. E., Banerjee, D., Shudo, Y., Lingala, B., Zhu, Y., Haddad, F., Woo, J. ELSEVIER SCIENCE INC. 2019: S216–S217

  View details for DOI 10.1016/j.healun.2019.01.527

  View details for Web of Science ID 000461365101212

• Impact of Concomitant Valvular Surgery on Patients Undergoing LVAD Implantation Mulumba, K. Y., Kasinpila, P., Fong, R., Kong, S., Hecker, L., Nissan, R., Banerjee, D., Teuteberg, J., Shudo, Y., Woo, Y., Hiesinger, W. ELSEVIER SCIENCE INC. 2019: S72–S73

  View details for DOI 10.1016/j.healun.2019.01.164

  View details for Web of Science ID 000461365100155

• Impact of Surgical Approach in Double Lung Transplantation: Median Sternotomy Decreases Operative and Cardiopulmonary Bypass Time Compared to Clamshell Thoracotomy Shudo, Y., Rinewalt, D., Lingala, B., Kim, F. Y., He, H., Boyd, J. H., Lee, A. M., Hiesinger, W., Currie, M. E., MacArthur, J. W., Woo, J. ELSEVIER SCIENCE INC. 2019: S414

  View details for DOI 10.1016/j.healun.2019.01.1054

  View details for Web of Science ID 000461365103045

• Successful Heart-Lung Transplant for a Patient on Continuous-Flow Left Ventricular Assist Device Support Complicated With Amiodarone-Induced Pulmonary Fibrosis TRANSPLANTATION PROCEEDINGS Currie, M. E., Shudo, Y., Mooney, J., Woo, Y. J. 2019; 51 (2): 593–94

  View details for DOI 10.1016/j.transproceed.2018.12.024

  View details for Web of Science ID 000473378100086

• The bicaval Wythenshawe technique in 2018-Reply to Dimarakis and Venkateswaran EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Shudo, Y., Wang, H., Woo, Y. 2019; 55 (3): 596

  View details for DOI 10.1093/ejcts/ezy280

  View details for Web of Science ID 000462721200038

• Successful Heart-Lung Transplant for a Patient on Continuous-Flow Left Ventricular Assist Device Support Complicated With Amiodarone-Induced Pulmonary Fibrosis. Transplantation proceedings Currie, M. E., Shudo, Y., Mooney, J., Woo, Y. J. 2019; 51 (2): 593–94

  Abstract

  In this case report, we present a successful case of en bloc heart-lung transplant in a patient with advanced cardiopulmonary respiratory failure from amiodarone-associated pulmonary fibrosis that occurred post-left ventricular assist device implantation.

  View details for PubMedID 30879597

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

  Abstract

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

  View details for PubMedID 30796438

• Successful heart-lung-kidney and domino heart transplantation following veno-venous extracorporeal membrane oxygenation support INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY Zhu, Y., Shudo, Y., Lee, A. M., Woo, Y. 2019; 28 (2): 316–17

  View details for DOI 10.1093/icvts/ivy251

  View details for Web of Science ID 000467955400022

• Impact of "increased-risk'' donor hearts on transplant outcomes: A propensity-matched analysis JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Shudo, Y., Cohen, J. E., Lingala, B., He, H., Zhu, Y., Woo, Y. 2019; 157 (2): 603–10

  View details for DOI 10.1016/j.jtcvs.2018.08.120

  View details for Web of Science ID 000456169700056

• Heart-lung transplantation over the past 10 years: an up-to-date concept EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Shudo, Y., Kasinpila, P., Lingala, B., Kim, F. Y., Woo, Y. 2019; 55 (2): 304–8

  View details for DOI 10.1093/ejcts/ezy253

  View details for Web of Science ID 000462711700020

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

  Abstract

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

  View details for PubMedID 30669225

• 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

  Abstract

  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

• 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

  Abstract

  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

• Physical therapy in successful venoarterial extracorporeal membrane oxygenation bridge to orthotopic heart transplantation. Journal of cardiac surgery Rinewalt, D. n., Shudo, Y. n., Kawana, M. n., Woo, Y. J. 2019

  Abstract

  Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a temporary mechanical circulatory support system that may be used as a lifesaving therapy for patients in acute heart failure and as a bridge to definitive management. Physical therapy in these patients remains challenging, with limited protocols to guide practitioners.We describe a case of a 37-year-old gentleman who presented with familial cardiomyopathy and cardiogenic shock.Our patient underwent urgent peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) followed by successful heart transplantation. While on ECMO support he was enrolled in a physical therapy program that included the VitalGo Tilt Bed to improve lower body weight bearing while avoiding hip flexion and damage to the peripheral ECMO cannulae. The patient was discharged home expeditiously after heart transplant due to aggressive physical rehabilitation while on full VA-ECMO support.Early intensive physical rehabilitation is feasible and safe and may result in improved outcomes and expeditious discharge in VA ECMO patients. Protocol driven multidisciplinary physical therapy with a patient on femorally cannulated VA-ECMO retains the advantages of lower extremity peripheral cannulation while eliminating the risks of immobility. The new UNOS allocation system may result in a successful bridge to transplantation in patients on VA-ECMO due to the increased prioritization of this population to receive donor organs.

  View details for DOI 10.1111/jocs.14220

  View details for PubMedID 31441558

• Successful orthotopic heart transplantation in a patient with Marfan syndrome. Journal of cardiac surgery Ogawa, Y. n., Choi, C. W., Shudo, Y. n., Woo, Y. J. 2019

  Abstract

  Cardiovascular diseases represent the leading cause of mortality in patients with Marfan syndrome. Many treatments have been developed for patients with end-stage heart failure, among which orthotopic heart transplantation remains the gold standard. We report a successful orthotopic heart transplantation for a Marfan syndrome patient in end-stage heart failure.

  View details for DOI 10.1111/jocs.14129

  View details for PubMedID 31233233

• mpact of Donor Obesity on Outcomes After Orthotopic Heart Transplantation JOURNAL OF THE AMERICAN HEART ASSOCIATION Shudo, Y., Cohen, J. E., Lingala, B., He, H., Woo, Y. 2018; 7 (23)

  View details for DOI 10.1161/JAHA.118.010253

  View details for Web of Science ID 000452891400021

• Impact of Donor Obesity on Outcomes After Orthotopic Heart Transplantation. Journal of the American Heart Association Shudo, Y., Cohen, J. E., Lingala, B., He, H., Woo, Y. J. 2018; 7 (23): e010253

  Abstract

  Background The impact of donor obesity on the outcome of orthotopic heart transplantation has not been studied. The aim of this study was to investigate the impact of donor obesity on the outcomes of adult orthotopic heart transplantation recipients. Methods and Results Data were obtained from the United Network for Organ Sharing database. All adult (age ≥18 years) patients undergoing orthotopic heart transplantation from 2000 through 2016 were included (n=31920). We stratified the cohort by donor body mass index ( BMI ); 13015 patients (40.8%) received a heart from a normal-weight donor ( BMI 18.5-24.9), 11271 patients (35.3%) received a heart from an overweight donor ( BMI 25.0-29.9), 4910 patients (15.4%) received a heart from an obese donor ( BMI 30.0-34.9), and 2724 patients (8.5%) received a heart from an extremely obese donor ( BMI ≥35). The cohort of obese donors was older, included a higher incidence of diabetes mellitus, and had a higher creatinine. Our data also showed that the recipients of obese donor grafts were older, had a higher BMI , creatinine, percentage of diabetes mellitus, and longer total waiting period. There was no significant difference detected in the survival likelihood ( P=0.08) of patients based on a donor's BMI-based categorized cohort. There were no significant differences found in the overall survival probability among 4 groups in the adjusted survival analyses ( P=0.25). Conclusions This study demonstrated that patients receiving higher BMI donor hearts might not be subjected to an increased risk of death, at least during the short term after transplant, compared with those using the normal-weight donors.

  View details for PubMedID 30511896

• Operative Techniques and Pitfalls in Donor Heart-Lung Procurement. Transplantation proceedings Salna, M., Shudo, Y., Woo, Y. J. 2018; 50 (10): 3111–12

  Abstract

  BACKGROUND: Heart-lung transplantation is a well-established therapeutic modality for concomitant end-stage heart and lung failure. With growing organ scarcity, the rates of these transplants are declining, and center experience is waning.METHODS: With over 35 years of experience performing heart-lung transplantation, we describe our procurement protocol herein, as well as offer suggestions to avoid potential pitfalls in order to ensure technical excellence in harvesting these valuable grafts.RESULTS: Procurement issues most commonly arise with organ preservation and inadvertent damage to structures that are difficult to fully visualize.CONCLUSIONS: En-bloc heart-lung procurement can be taught effectively and safely to trainees with an emphasis on avoiding common pitfalls that may compromise graft function.

  View details for PubMedID 30577175

• Successful Outcome Following Orthotopic Heart Transplantation With a Donor Half Way Across The Country TRANSPLANTATION PROCEEDINGS Currie, M. E., Shudo, Y., Woo, Y. J. 2018; 50 (10): 4062–63

  View details for DOI 10.1016/j.transproceed.2018.09.014

  View details for Web of Science ID 000454972000196

• Operative Techniques and Pitfalls in Donor Heart-Lung Procurement TRANSPLANTATION PROCEEDINGS Salna, M., Shudo, Y., Woo, Y. J. 2018; 50 (10): 3111–12

  View details for DOI 10.1016/j.transproceed.2018.06.009

  View details for Web of Science ID 000454972000033

• Successful Outcome Following Orthotopic Heart Transplantation With a Donor Half Way Across The Country. Transplantation proceedings Currie, M. E., Shudo, Y., Woo, Y. J. 2018; 50 (10): 4062–63

  Abstract

  Orthotopic heart transplantation is the criterion standard treatment for end-stage heart failure and the number of recipient candidates has been increasing. Despite this increasing demand, there is limited donor organ supply. In order to surmount this challenge, we propose harvesting donor hearts from more distant locations and accepting longer cold ischemic times. The usual accepted total ischemic time limit for the transplanted human heart is up to 4 hours. Here, we report the successful use of a donor heart from 1268 miles away with a total allograft ischemic time greater than 6 hours.

  View details for PubMedID 30577315

• 50 Year Heart Transplantation Ultra Long-Term Outcomes - The Stanford Experience Zhu Yuanjia, Shudo, Y., Lingala, B., Yasukawa, L., Loh, E., Oyer, P. E., Woo, Y. J. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000528619403468

• Planned Concomitant Left and Right Ventricular Assist Device Insertion to Avoid Long-term Biventricular Mechanical Support: Bridge to Right Ventricular Recovery. The heart surgery forum Salna, M., Shudo, Y., Teuteberg, J. J., Banerjee, D., Ha, R. V., Woo, Y. J., Hiesinger, W. 2018; 21 (5): E412–E414

  Abstract

  INTRODUCTION: The planned use of a temporary right ventricular assist device (RVAD) at the time of left ventricular assist device (LVAD) implantation may prevent the need for a permanent biventricular assist device (BiVAD). Herein we describe our RVAD weaning protocol that was effectively employed in 4 patients to prevent the need for permanent BiVAD.METHODS: Four patients in refractory cardiogenic shock underwent planned RVAD insertion during LVAD implantation due to severely depressed right ventricular function with dilation preoperatively. A standardized RVAD weaning protocol was employed in these 4 patients in preparation for decannulation.RESULTS: Temporary RVADs were successfully placed in all 4 patients at the time of LVAD implantation. All patients survived to RVAD decannulation and discharge and were alive at the time of most recent follow-up (range, 528-742 days post-RVAD decannulation).CONCLUSION: Planned implantation of a temporary RVAD in high risk patients may avoid the need for biventricular mechanical support in the future.

  View details for PubMedID 30311895

• Heart-lung transplantation over the past 10 years: an up-to-date concept. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Shudo, Y., Kasinpila, P., Lingala, B., Kim, F. Y., Woo, Y. J. 2018

  Abstract

  OBJECTIVES: Heart-lung transplantation has been established as an effective treatment for patients with advanced cardiopulmonary failure. Over the years, the number of operations performed has declined. In 2015, only 38 adult heart-lung transplants were reported worldwide. Since then, we have performed 16 operations in high-acuity patients with excellent postoperative outcomes. Herein, we review our single-centre experience with heart-lung transplantation over the past 10 years.METHODS: We retrospectively reviewed 49 heart-lung transplant recipients between 2008 and 2018 to investigate the patient characteristics and outcomes while comparing those results across 2 cohorts (2008-2015, Era I, n=30 and 2016-2018, Era II, n=19).RESULTS: Our patient demographics and waitlist time did not significantly change over time. However, the lung allocation score was significantly higher in Era II compared to Era I (51.1±19.8 in Era II and 41.6±19.5 in Era I; P=0.006). We also observed a higher rate-while not statistically significant-of preoperative and postoperative use of mechanical circulatory support in the present era. Although there is a trend of higher acuity in the present era, we continue to have excellent outcomes with 100% 30-day and 1-year survival.CONCLUSIONS: These results suggest that in a high-volume heart-lung transplant programme, excellent postoperative outcomes can be achieved even in patients with rapid and severe cardiopulmonary decline and that, to this day, heart-lung transplantation remains a viable option for patients with advanced cardiopulmonary disease.

  View details for PubMedID 30260389

• Ambulating femoral venoarterial extracorporeal membrane oxygenation bridge to heart-lung transplant JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Shudo, Y., Kasinpila, P., Lee, A. M., Rao, V. K., Woo, Y. 2018; 156 (3): E135–E137

  View details for DOI 10.1016/j.jtcvs.2018.03.002

  View details for Web of Science ID 000441556000001

• Reply to Dimarakis and Venkateswaran. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Shudo, Y., Wang, H., Woo, Y. J. 2018

  View details for PubMedID 30113629

• Successful heart-lung-kidney and domino heart transplantation following veno-venous extracorporeal membrane oxygenation support. Interactive cardiovascular and thoracic surgery Zhu, Y., Shudo, Y., Lee, A. M., Woo, Y. J. 2018

  Abstract

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

  View details for PubMedID 30113636

• Prolonged veno-arterial extracorporeal life support for cardiac failure INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS Guenther, S. W., Shudo, Y., Hiesinger, W., Banerjee, D. 2018; 41 (8): 437–44

  View details for DOI 10.1177/0391398818777359

  View details for Web of Science ID 000439618800003

• Heart transplant after profoundly extended ambulatory central venoarterial extracorporeal membrane oxygenation JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Shudo, Y., Wang, H., Ha, R. V., Hayes, A. D., Woo, Y. 2018; 156 (1): E7–E9

  View details for DOI 10.1016/j.jtcvs.2018.02.001

  View details for Web of Science ID 000436592600003

• Impact of load variations on systolic function of failed left ventricle under extracorporeal membrane oxygenation assessed by strain and tissue doppler imaging Ouazani, N., Shudo, Y., Sallam, K., Lee, A., Boyd, J., Teuteberg, J. WILEY. 2018: 114–15

  View details for Web of Science ID 000434123900311

• Ambulating femoral venoarterial extracorporeal membrane oxygenation bridge to heart-lung transplant. The Journal of thoracic and cardiovascular surgery Shudo, Y., Kasinpila, P., Lee, A. M., Rao, V. K., Woo, Y. J. 2018

  View details for PubMedID 29628344

• 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

• Prolonged veno-arterial extracorporeal life support for cardiac failure. The International journal of artificial organs Guenther, S. P., Shudo, Y. n., Hiesinger, W. n., Banerjee, D. n. 2018: 391398818777359

  Abstract

  In intractable cardiogenic shock, extracorporeal life support frequently is the last treatment option. Outcomes of prolonged veno-arterial extracorporeal life support for cardiac failure are poorly defined.We retrospectively analyzed 10 patients (4 females, age = 36 ± 16 years) who underwent prolonged extracorporeal life support (≥7 days) from December 2015 to March 2017 for cardiogenic shock. The primary endpoint was survival to hospital discharge.Etiologies included ischemic cardiomyopathy with non ST-segment elevation myocardial infarction (n = 1), dilated (n = 3), hypertrophic (n = 1), postpartum cardiomyopathy (n = 1), and others (n = 4). Heart failure was left or biventricular in 80.0% (left ventricular ejection fraction = 15.6 ± 5.5%). Among the 10 patients, 80.0% underwent femoral and 20.0% central cannulation, 40.0% required changes in the cannulation strategy, and 80.0% underwent left ventricular venting. No technical malfunctions occurred, but 50.0% required circuit exchanges for thrombus formation. 80.0% suffered from infections. 60.0% could be decannulated after 717 ± 830 (168-2301) h of support, and survival to hospital discharge was 40.0%. Longest follow-up available is 160 ± 175 (12-409) days after discharge, with 30.0% alive and in satisfying functional condition.Prolonged veno-arterial extracorporeal life support for cardiac failure is feasible with low technical complication rates. Survival rates are acceptable, yet inferior to short-term support. We observed a shift from initial shock-related complications to infections during prolonged support. Since recovery and thus weaning is rather unlikely after a prolonged need for extracorporeal life support, this form of support should be limited to centers offering the full spectrum of interdisciplinary cardiac care including ventricular assist device implantation and transplantation.

  View details for PubMedID 29896993

• Planned Concomitant Left and Right Ventricular Assist Device Insertion to Avoid Long-term Biventricular Mechanical Support: Bridge to Right Ventricular Recovery HEART SURGERY FORUM Salna, M., Shudo, Y., Teuteberg, J. J., Banerjee, D., Ha, R. V., Woo, Y., Hiesinger, W. 2018; 21 (5): E412–E414

  View details for DOI 10.1532/hsf.2035

  View details for Web of Science ID 000457932600016

• Gene expression profiling of acute type A aortic dissection combined with in vitroassessment†. European journal of cardio-thoracic surgery Kimura, N., Futamura, K., Arakawa, M., Okada, N., Emrich, F., Okamura, H., Sato, T., Shudo, Y., Koyano, T. K., Yamaguchi, A., Adachi, H., Matsuda, A., Kawahito, K., Matsumoto, K., Fischbein, M. P. 2017

  Abstract

  The mechanisms underlying aortic dissection remain to be fully elucidated. We aimed to identify key molecules driving dissection through gene expression profiling achieved by microarray analysis and subsequent in vitro experiments using human aortic endothelial cells (HAECs) and aortic vascular smooth muscle cells (AoSMCs).Total RNA, including microRNA (miRNA), was isolated from the intima-media layer of dissected ascending aorta obtained intraoperatively from acute type A aortic dissection (ATAAD) patients without familial thoracic aortic disease ( n  = 8) and that of non-dissected ascending aorta obtained from transplant donors ( n  = 9). Gene expression profiling was performed with mRNA and miRNA microarrays, and results were confirmed by quantitative polymerase chain reaction (qPCR). Target genes and miRNA were identified by gene ontology analysis and a literature search. To reproduce the in silico results, HAECs and AoSMCs were stimulated in vitro by upstream cytokines, and expression of target genes was assessed by qPCR.Microarray analysis revealed 1536 genes (3.6%, 1536/42 545 probes) and 41 miRNAs (3.0%, 41/1368 probes) that were differentially expressed in the ATAAD group (versus donor group). The top 15 related pathways included regulation of inflammatory response, growth factor activity and extracellular matrix. Gene ontology analysis identified JAK2 (regulation of inflammatory response), PDGFA, TGFB1, VEGFA (growth factor activity) and TIMP3 , TIMP4, SERPINE1 (extracellular matrix) as the target genes and miR-21-5p, a TIMP3 repressor, as target miRNA that interacts with the target genes. Validation qPCR confirmed the altered expression of all 7 target genes and miR-21-5p in dissected aorta specimens (all genes, P  < 0.05). Ingenuity pathway analysis showed TNF-α and TGF-β to be upstream cytokines for the target genes. In vitro experiments showed these cytokines inhibit TIMP3 expression ( P  < 0.05) and enhance VEGFA expression ( P  < 0.01) in AoSMCs but not HAECs. miR-21-5p expression increases in AoSMCs under TNF-α and TGF-β stimulation (fold change: 1.36; P  = 0.011).Results of our novel approach, integrating in vitro assessment into gene expression profiling, implicated chronic inflammation characterized by MMP-TIMP dysregulation, increased VEGFA expression, and TGF-β signalling in the development of dissection. Further investigation may reveal novel diagnostic biomarkers and uncover the mechanism(s) underlying ATAAD.

  View details for DOI 10.1093/ejcts/ezx095

  View details for PubMedID 28402522

• Surgical Strategy to Support Right Ventricle with HVAD RVAD: Right Atrial vs Right Ventricular Diaphragmatic Surface Cannulation Shudo, Y., Ha, R. V., Reinhartz, O., Woo, J., Boyd, J., Almond, C., Rosenthal, D. N., Chen, S., Maeda, K. ELSEVIER SCIENCE INC. 2017: S29

  View details for Web of Science ID 000398839800054

• Current status of domino heart transplantation. Journal of cardiac surgery Shudo, Y., Ma, M., Boyd, J. H., Woo, Y. J. 2017; 32 (3): 229-232

  Abstract

  Domino heart transplant, wherein the explanted heart from the recipient of an en-bloc heart-lung is utilized for a second recipient, represents a unique surgical strategy for patients with end-stage heart failure. With a better understanding of the potential advantages and disadvantages of this procedure, its selective use in the current era can improve and maximize organ allocation in the United States. In this report, we reviewed the current status of domino heart transplantation.

  View details for DOI 10.1111/jocs.13104

  View details for PubMedID 28219115

• Adipose tissue-derived multi-lineage progenitor cells improve left ventricular dysfunction in porcine ischemic cardiomyopathy model JOURNAL OF HEART AND LUNG TRANSPLANTATION Shudo, Y., Miyagawa, S., Ohkura, H., Fukushima, S., Saito, A., Kawaguchi, N., Matsuura, N., Toda, K., Sakaguchi, T., Nishi, H., Yoshikawa, Y., Shimizu, T., Okano, T., Matsuyama, A., Sawa, Y. 2017; 36 (2): 237-239

  View details for DOI 10.1016/j.healun.2016.11.012

  View details for Web of Science ID 000393532500016

  View details for PubMedID 28159019

• Successful use of donor lungs after repairing severely injured pulmonary vein of donor lungs. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Shudo, Y. n., Miller, S. L., Boyd, J. H., Woo, Y. J. 2017

  View details for PubMedID 29186381

• An innovative biologic system for photon-powered myocardium in the ischemic heart. Science advances Cohen, J. E., Goldstone, A. B., Paulsen, M. J., Shudo, Y. n., Steele, A. N., Edwards, B. B., Patel, J. B., MacArthur, J. W., Hopkins, M. S., Burnett, C. E., Jaatinen, K. J., Thakore, A. D., Farry, J. M., Truong, V. N., Bourdillon, A. T., Stapleton, L. M., Eskandari, A. n., Fairman, A. S., Hiesinger, W. n., Esipova, T. V., Patrick, W. L., Ji, K. n., Shizuru, J. A., Woo, Y. J. 2017; 3 (6): e1603078

  Abstract

  Coronary artery disease is one of the most common causes of death and disability, afflicting more than 15 million Americans. Although pharmacological advances and revascularization techniques have decreased mortality, many survivors will eventually succumb to heart failure secondary to the residual microvascular perfusion deficit that remains after revascularization. We present a novel system that rescues the myocardium from acute ischemia, using photosynthesis through intramyocardial delivery of the cyanobacterium Synechococcus elongatus. By using light rather than blood flow as a source of energy, photosynthetic therapy increases tissue oxygenation, maintains myocardial metabolism, and yields durable improvements in cardiac function during and after induction of ischemia. By circumventing blood flow entirely to provide tissue with oxygen and nutrients, this system has the potential to create a paradigm shift in the way ischemic heart disease is treated.

  View details for PubMedID 28630913

• Layered smooth muscle cell-endothelial progenitor cell sheets derived from the bone marrow augment postinfarction ventricular function. The Journal of thoracic and cardiovascular surgery Shudo, Y. n., Goldstone, A. B., Cohen, J. E., Patel, J. B., Hopkins, M. S., Steele, A. N., Edwards, B. B., Kawamura, M. n., Miyagawa, S. n., Sawa, Y. n., Woo, Y. J. 2017; 154 (3): 955–63

  Abstract

  The angiogenic potential of endothelial progenitor cells (EPCs) may be limited by the absence of their natural biologic foundation, namely smooth muscle pericytes. We hypothesized that joint delivery of EPCs and smooth muscle cells (SMCs) in a novel, totally bone marrow-derived cell sheet will mimic the native architecture of a mature blood vessel and act as an angiogenic construct to limit post infarction ventricular remodeling.Primary EPCs and mesenchymal stem cells were isolated from bone marrow of Wistar rats. Mesenchymal stem cells were transdifferentiated into SMCs by culture on fibronectin-coated culture dishes. Confluent SMCs topped with confluent EPCs were detached from an Upcell dish to create a SMC-EPC bi-level cell sheet. A rodent model of ischemic cardiomyopathy was then created by ligating the left anterior descending artery. Rats were randomized into 3 groups: cell sheet transplantation (n = 9), no treatment (n = 12), or sham surgery control (n = 7).Four weeks postinfarction, mature vessel density tended to increase in cell sheet-treated animals compared with controls. Cell sheet therapy significantly attenuated the extent of cardiac fibrosis compared with that of the untreated group (untreated vs cell sheet, 198 degrees [interquartile range (IQR), 151-246 degrees] vs 103 degrees [IQR, 92-113 degrees], P = .04). Furthermore, EPC-SMC cell sheet transplantation attenuated myocardial dysfunction, as evidenced by an increase in left ventricular ejection fraction (untreated vs cell sheet vs sham, 33.5% [IQR, 27.8%-35.7%] vs 45.9% [IQR, 43.6%-48.4%] vs 59.3% [IQR, 58.8%-63.5%], P = .001) and decreases in left ventricular dimensions.The bone marrow-derived, spatially arranged SMC-EPC bi-level cell sheet is a novel, multilineage cellular therapy obtained from a translationally practical source. Interactions between SMCs and EPCs augment mature neovascularization, limit adverse remodeling, and improve ventricular function after myocardial infarction.

  View details for PubMedID 28651946

• 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

  Abstract

  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

• Percutaneous, minimally invasive approach to implantable left ventricular assist device deactivation. The Journal of thoracic and cardiovascular surgery Kidambi, S. n., Shudo, Y. n., Dake, M. D., Woo, Y. J., Ha, R. V. 2017

  View details for PubMedID 29102456

• Operative technique and pitfalls in donor heart procurement. Asian cardiovascular & thoracic annals Shudo, Y., Hiesinger, W., Oyer, P. E., Woo, Y. J. 2017; 25 (1): 80-82

  Abstract

  We describe a simple and reproducible donor heart procurement technique in sequential steps. A detailed understanding of procurement and organ preservation techniques should be an essential part of a heart transplant training program.

  View details for DOI 10.1177/0218492316678716

  View details for PubMedID 28074702

• A modified explant technique of HeartWare ventricular assist device for bridge to recovery. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Shudo, Y. n., Choi, C. W., Woo, Y. J., Ha, R. V. 2017

  Abstract

  The HeartWare left ventricular assist device is a miniaturized, continuous centrifugal-flow pump. The implantation technique is well described and relatively standardized across different institutions. However, there still exists a technical concern about handling the inflow cannula at the time of device explant. Specifically, the removal of the sewing ring and plicating the apical defect en masse may distort the geometry of the left ventricle and impart myocardial dysfunction. Additionally, a prefabricated repair mechanism by the manufacturer is not readily available in all countries (i.e. USA). Here, we describe a technique to address the apical core defect, using a tailor-made plug and leaving the sewing ring in situ, at the time of the HeartWare left ventricular assist device explant.

  View details for PubMedID 28950296

• 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

  Abstract

  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

• A modified implantation technique of left ventricular assist device: optimal outflow tract positioning. International journal of cardiology Shudo, Y., Choi, C. W., Woo, Y. J., Ha, R. V. 2016; 223: 776-778

  View details for DOI 10.1016/j.ijcard.2016.08.209

  View details for PubMedID 27573606

• Isolation and trans-differentiation of mesenchymal stromal cells into smooth muscle cells: Utility and applicability for cell-sheet engineering. Cytotherapy Shudo, Y., Cohen, J. E., Goldstone, A. B., MacArthur, J. W., Patel, J., Edwards, B. B., Hopkins, M. S., Steele, A. N., Joubert, L., Miyagawa, S., Sawa, Y., Woo, Y. J. 2016; 18 (4): 510-517

  Abstract

  Bone marrow (BM)-derived mesenchymal stromal cells (MSCs) have shown potential to differentiate into various cell types, including smooth muscle cells (SMCs). The extracellular matrix (ECM) represents an appealing and readily available source of SMCs for use in tissue engineering. In this study, we hypothesized that the ECM could be used to induce MSC differentiation to SMCs for engineered cell-sheet construction.Primary MSCs were isolated from the BM of Wistar rats, transferred and cultured on dishes coated with 3 different types of ECM: collagen type IV (Col IV), fibronectin (FN), and laminin (LM). Primary MSCs were also included as a control. The proportions of SMC (a smooth muscle actin [aSMA] and SM22a) and MSC markers were examined with flow cytometry and Western blotting, and cell proliferation rates were also quantified.Both FN and LM groups were able to induce differentiation of MSCs toward smooth muscle-like cell types, as evidenced by an increase in the proportion of SMC markers (aSMA; Col IV 42.3 ± 6.9%, FN 65.1 ± 6.5%, LM 59.3 ± 7.0%, Control 39.9 ± 3.1%; P = 0.02, SM22; Col IV 56.0 ± 7.7%, FN 74.2 ± 6.7%, LM 60.4 ± 8.7%, Control 44.9 ± 3.6%) and a decrease in that of MSC markers (CD105: Col IV 64.0 ± 5.2%, FN 57.6 ± 4.0%, LM 60.3 ± 7.0%, Control 85.3 ± 4.2%; P = 0.03). The LM group showed a decrease in overall cell proliferation, whereas FN and Col IV groups remained similar to control MSCs (Col IV, 9.0 ± 2.3%; FN, 9.8 ± 2.5%; LM, 4.3 ± 1.3%; Control, 9.8 ± 2.8%).Our findings indicate that ECM selection can guide differentiation of MSCs into the SMC lineage. Fibronectin preserved cellular proliferative capacity while yielding the highest proportion of differentiated SMCs, suggesting that FN-coated materials may be facilitate smooth muscle tissue engineering.

  View details for DOI 10.1016/j.jcyt.2016.01.012

  View details for PubMedID 26971679

• A Tissue-Engineered Chondrocyte Cell Sheet Induces Extracellular Matrix Modification to Enhance Ventricular Biomechanics and Attenuate Myocardial Stiffness in Ischemic Cardiomyopathy TISSUE ENGINEERING PART A Shudo, Y., Cohen, J. E., MacArthur, J. W., Goldstone, A. B., Otsuru, S., Trubelja, A., Patel, J., Edwards, B. B., Hung, G., Fairman, A. S., Brusalis, C., Hiesinger, W., Atluri, P., Hiraoka, A., Miyagawa, S., Sawa, Y., Woo, Y. J. 2015; 21 (19-20): 2515-2525

  Abstract

  There exists a substantial body of work describing cardiac support devices to mechanically support the left ventricle (LV); however, these devices lack biological effects. To remedy this, we implemented a cell sheet engineering approach utilizing chondrocytes, which in their natural environment produce a relatively elastic extracellular matrix (ECM) for a cushioning effect. Therefore, we hypothesized that a chondrocyte cell sheet applied to infarcted and borderzone myocardium will biologically enhance the ventricular ECM and increase elasticity to augment cardiac function in a model of ischemic cardiomyopathy (ICM). Primary articular cartilage chondrocytes of Wistar rats were isolated and cultured on temperature-responsive culture dishes to generate cell sheets. A rodent ICM model was created by ligating the left anterior descending coronary artery. Rats were divided into two groups: cell sheet transplantation (1.0 × 10(7) cells/dish) and no treatment. The cell sheet was placed onto the surface of the heart covering the infarct and borderzone areas. At 4 weeks following treatment, the decreased fibrotic extension and increased elastic microfiber networks in the infarct and borderzone areas correlated with this technology's potential to stimulate ECM formation. The enhanced ventricular elasticity was further confirmed by the axial stretch test, which revealed that the cell sheet tended to attenuate tensile modulus, a parameter of stiffness. This translated to increased wall thickness in the infarct area, decreased LV volume, wall stress, mass, and improvement of LV function. Thus, the chondrocyte cell sheet strengthens the ventricular biomechanical properties by inducing the formation of elastic microfiber networks in ICM, resulting in attenuated myocardial stiffness and improved myocardial function.

  View details for DOI 10.1089/ten.tea.2014.0155

  View details for PubMedID 26154752

• B-type natriuretic peptide response and reverse left ventricular remodeling after surgical correction of functional mitral regurgitation in patients with advanced cardiomyopathy. Journal of cardiology Kainuma, S., Taniguchi, K., Toda, K., Shudo, Y., Takeda, K., Funatsu, T., Miyagawa, S., Kondoh, H., Nishi, H., Yoshikawa, Y., Fukushima, S., Hamada, S., Kubo, K., Daimon, T., Sawa, Y. 2015; 66 (4): 279-285

  Abstract

  Restrictive mitral annuloplasty (RMA) can reverse left ventricular (LV) remodeling and reduce plasma B-type natriuretic peptide (BNP), a surrogate biomarker of heart failure. However, the relationship between reverse LV remodeling and plasma BNP changes after RMA is poorly defined. We explored the main hemodynamic factors contributing to change in plasma BNP after RMA in patients with functional mitral regurgitation (MR).Twenty-four patients with moderate to severe functional MR secondary to LV systolic dysfunction [ejection fraction (EF) <40%] underwent 64-row multidetector computed tomography (MDCT) before and 1.4 months after RMA. LV end-diastolic volume index (EDVI), end-systolic volume index (ESVI), LVEF, and regional and global end-systolic wall stress (ESS) were calculated from 3-dimensional MDCT images, with blood samples for plasma BNP measurement collected the same day.After RMA, LV volumes and global ESS were decreased, while LVEF improved (all p<0.01). There were significant correlations between changes in LVEDVI and LVESVI (r=0.90, p<0.0001), LVESVI and global ESS (r=0.54, p=0.006), and global ESS and LVEF (r=-0.60, p=0.002). The median value for the plasma BNP also decreased from 597 pg/ml [interquartile range (IQR), 360-934 pg/ml] to 207 pg/ml (IQR, 124-271 pg/ml), in association with changes in LVEDVI (r=0.47, p=0.019), LVESVI (r=0.56, p=0.004), LVEF (r=-0.60, p=0.002), and global ESS (r=0.74, p<0.0001). Multivariate regression analysis showed that global ESS change was the strongest contributor to change in natural-log-transformed plasma BNP (standardized partial regression coefficient=0.59, p=0.004), indicating a strong association between decrease in LV afterload and reduction in plasma BNP level after RMA.There may be a significant association between LV reverse remodeling and plasma BNP change after RMA. Furthermore, LV end-systolic myocardial stress may be the key mechanical stimulus influencing plasma BNP after surgical correction for functional MR. Whether these favorable BNP responses and reverse remodeling can predict improved survival requires further study.

  View details for DOI 10.1016/j.jjcc.2015.02.015

  View details for PubMedID 25851471

• Evaluation of late aortic insufficiency with continuous flow left ventricular assist device†. European journal of cardio-thoracic surgery Hiraoka, A., Cohen, J. E., Shudo, Y., Macarthur, J. W., Howard, J. L., Fairman, A. S., Atluri, P., Kirkpatrick, J. N., Woo, Y. J. 2015; 48 (3): 400-406

  Abstract

  The aim of this study was to evaluate late development of aortic insufficiency (AI) with continuous flow left ventricular assist device (CLVAD). Development of AI is an increasingly recognized important complication in CLVAD therapy, but there are still few reports about this topic.We analysed data from 99 patients who underwent CLVAD implantation. De novo AI was defined as the development of mild or greater AI in patients with none or trace preoperative AI. Anatomic and functional correlates of de novo AI were investigated.Among the 17 patients with preoperative mild AI, no improvements were observed in mitral regurgitation or LV end-systolic dimension. Of the remaining 82 patients, de novo AI was identified in 43 patients (52%), on the most recent follow-up echocardiography, and did not influence survival nor improvement of LV geometry. Rate of freedom from de novo AI at 1 year after CLVAD implantation was 35.9%. Development of significantly greater AI was observed in patients without valve opening (AI grade 1.3 ± 1.0 vs 0.7 ± 0.9; P = 0.005). By multivariate Cox hazard model, smaller body surface area (BSA) [hazard ratio: 0.83 [95% confidence interval (CI): 0.72-0.97], P = 0.018], larger aortic root diameter (AOD) [hazard ratio: 1.11 (95% CI: 1.02-1.22), P = 0.012] and higher pulmonary artery systolic pressure (PASP) [hazard ratio: 1.24 (95% CI: 1.10-1.41), P < 0.001] were identified as the independent preoperative risk factors for de novo AI. In a subset of patients with speed adjustments, increase of CLVAD speed worsened AI and led to insufficient LV unloading in patients with aortic dilatation (AOD ≥ 3.5 cm).Any significant mortality difference related to preoperative or development of postimplant AI was not found. AI was associated with changes in LV size, and there appears to be an interaction between BSA, preoperative PASP, time since implant, aortic valve opening, aortic size and development of AI. Longitudinal clinical management in CLVAD patients, particularly in terms of CLVAD speed optimization, should include careful assessment.

  View details for DOI 10.1093/ejcts/ezu507

  View details for PubMedID 25653250

• Non-resectional leaflet remodeling mitral valve repair preserves leaflet mobility: A quantitative echocardiographic analysis of mitral valve configuration INTERNATIONAL JOURNAL OF CARDIOLOGY Shudo, Y., Cohen, J. E., MacArthur, J. W., Goldstone, A. B., Hiraoka, A., Howard, J., Fairman, A. S., Patel, J., Edwards, B. B., Atluri, P., Woo, Y. J. 2015; 186: 16-18

  View details for DOI 10.1016/j.ijcard.2015.03.239

  View details for PubMedID 25804458

• A Novel Minimally Invasive Ovine Model of Ischemic Cardiomyopathy With Advanced Cardiac Imaging Yields Superior Results and Survival 35th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-Lung-Transplantation Cohen, J. E., Goldstone, A. B., Shudo, Y., MacArthur, J. W., Patel, J. B., EDWARDS, B. B., PATRICK, W. L., Aribeana, C. N., Woo, Y. ELSEVIER SCIENCE INC. 2015: S180–S180

  View details for Web of Science ID 000353251500465

• Bioengineered Stromal Cell- Derived Factor-1 alpha Analogue Delivered as an Angiogenic Therapy Significantly Restores Viscoelastic Material Properties of Infarcted Cardiac Muscle JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME Trubelja, A., MacArthur, J. W., Sarver, J. J., Cohen, J. E., Hung, G., Shudo, Y., Fairman, A. S., Patel, J., Edwards, B. B., Damrauer, S. M., Hiesinger, W., Atluri, P., Woo, Y. J. 2014; 136 (8)

  Abstract

  Ischemic heart disease is a major health problem worldwide, and current therapies fail to address microrevascularization. Previously, our group demonstrated that the sustained release of novel engineered stromal cell-derived factor 1-a analogue (ESA) limits infarct spreading, collagen deposition, improves cardiac function by promoting angiogenesis in the region surrounding the infarct, and restores the tensile properties of infarcted myocardium. In this study, using a well-established rat model of ischemic cardiomyopathy, we describe a novel and innovative method for analyzing the viscoelastic properties of infarcted myocardium. Our results demonstrate that, compared with a saline control group, animals treated with ESA have significantly improved myocardial relaxation rates, while reducing the transition strain, leading to restoration of left ventricular mechanics.

  View details for DOI 10.1115/1.4027731

  View details for Web of Science ID 000338507000012

• A bioengineered hydrogel system enables targeted and sustained intramyocardial delivery of neuregulin, activating the cardiomyocyte cell cycle and enhancing ventricular function in a murine model of ischemic cardiomyopathy. Circulation. Heart failure Cohen, J. E., Purcell, B. P., Macarthur, J. W., Mu, A., Shudo, Y., Patel, J. B., Brusalis, C. M., Trubelja, A., Fairman, A. S., Edwards, B. B., Davis, M. S., Hung, G., Hiesinger, W., Atluri, P., Margulies, K. B., Burdick, J. A., Woo, Y. J. 2014; 7 (4): 619-626

  Abstract

  Neuregulin-1β (NRG) is a member of the epidermal growth factor family possessing a critical role in cardiomyocyte development and proliferation. Systemic administration of NRG demonstrated efficacy in cardiomyopathy animal models, leading to clinical trials using daily NRG infusions. This approach is hindered by requiring daily infusions and off-target exposure. Therefore, this study aimed to encapsulate NRG in a hydrogel to be directly delivered to the myocardium, accomplishing sustained localized NRG delivery.NRG was encapsulated in hydrogel, and release over 14 days was confirmed by ELISA in vitro. Sprague-Dawley rats were used for cardiomyocyte isolation. Cells were stimulated by PBS, NRG, hydrogel, or NRG-hydrogel (NRG-HG) and evaluated for proliferation. Cardiomyocytes demonstrated EdU (5-ethynyl-2'-deoxyuridine) and phosphorylated histone H3 positivity in the NRG-HG group only. For in vivo studies, 2-month-old mice (n=60) underwent left anterior descending coronary artery ligation and were randomized to the 4 treatment groups mentioned. Only NRG-HG-treated mice demonstrated phosphorylated histone H3 and Ki67 positivity along with decreased caspase-3 activity compared with all controls. NRG was detected in myocardium 6 days after injection without evidence of off-target exposure in NRG-HG animals. At 2 weeks, the NRG-HG group exhibited enhanced left ventricular ejection fraction, decreased left ventricular area, and augmented borderzone thickness.Targeted and sustained delivery of NRG directly to the myocardial borderzone augments cardiomyocyte mitotic activity, decreases apoptosis, and greatly enhances left ventricular function in a model of ischemic cardiomyopathy. This novel approach to NRG administration avoids off-target exposure and represents a clinically translatable strategy in myocardial regenerative therapeutics.

  View details for DOI 10.1161/CIRCHEARTFAILURE.113.001273

  View details for PubMedID 24902740

• Preclinical evaluation of the engineered stem cell chemokine stromal cell-derived factor 1a analog in a translational ovine myocardial infarction model. Circulation research Macarthur, J. W., Cohen, J. E., McGarvey, J. R., Shudo, Y., Patel, J. B., Trubelja, A., Fairman, A. S., Edwards, B. B., Hung, G., Hiesinger, W., Goldstone, A. B., Atluri, P., Wilensky, R. L., Pilla, J. J., Gorman, J. H., Gorman, R. C., Woo, Y. J. 2014; 114 (4): 650-659

  Abstract

  After myocardial infarction, there is an inadequate blood supply to the myocardium, and the surrounding borderzone becomes hypocontractile.To develop a clinically translatable therapy, we hypothesized that in a preclinical ovine model of myocardial infarction, the modified endothelial progenitor stem cell chemokine, engineered stromal cell-derived factor 1α analog (ESA), would induce endothelial progenitor stem cell chemotaxis, limit adverse ventricular remodeling, and preserve borderzone contractility.Thirty-six adult male Dorset sheep underwent permanent ligation of the left anterior descending coronary artery, inducing an anteroapical infarction, and were randomized to borderzone injection of saline (n=18) or ESA (n=18). Ventricular function, geometry, and regional strain were assessed using cardiac MRI and pressure-volume catheter transduction. Bone marrow was harvested for in vitro analysis, and myocardial biopsies were taken for mRNA, protein, and immunohistochemical analysis. ESA induced greater chemotaxis of endothelial progenitor stem cells compared with saline (P<0.01) and was equivalent to recombinant stromal cell-derived factor 1α (P=0.27). Analysis of mRNA expression and protein levels in ESA-treated animals revealed reduced matrix metalloproteinase 2 in the borderzone (P<0.05), with elevated levels of tissue inhibitor of matrix metalloproteinase 1 and elastin in the infarct (P<0.05), whereas immunohistochemical analysis of borderzone myocardium showed increased capillary and arteriolar density in the ESA group (P<0.01). Animals in the ESA treatment group also had significant reductions in infarct size (P<0.01), increased maximal principle strain in the borderzone (P<0.01), and a steeper slope of the end-systolic pressure-volume relationship (P=0.01).The novel, biomolecularly designed peptide ESA induces chemotaxis of endothelial progenitor stem cells, stimulates neovasculogenesis, limits infarct expansion, and preserves contractility in an ovine model of myocardial infarction.

  View details for DOI 10.1161/CIRCRESAHA.114.302884

  View details for PubMedID 24366171

• Addition of Mesenchymal Stem Cells Enhances the Therapeutic Effects of Skeletal Myoblast Cell-Sheet Transplantation in a Rat Ischemic Cardiomyopathy Model TISSUE ENGINEERING PART A Shudo, Y., Miyagawa, S., Ohkura, H., Fukushima, S., Saito, A., Shiozaki, M., Kawaguchi, N., Matsuura, N., Shimizu, T., Okano, T., Matsuyama, A., Sawa, Y. 2014; 20 (3-4): 728-739

  Abstract

  Functional skeletal myoblasts (SMBs) are transplanted into the heart effectively and safely as cell sheets, which induce functional recovery in myocardial infarction (MI) patients without lethal arrhythmia. However, their therapeutic effect is limited by ischemia. Mesenchymal stem cells (MSCs) have prosurvival/proliferation and antiapoptotic effects on co-cultured cells in vitro. We hypothesized that adding MSCs to the SMB cell sheets might enhance SMB survival post-transplantation and improve their therapeutic effects.Cell sheets of primary SMBs of male Lewis rats (r-SMBs), primary MSCs of human female fat tissues (h-MSCs), and their co-cultures were generated using temperature-responsive dishes. The levels of candidate paracrine factors, rat hepatocyte growth factor and vascular endothelial growth factor, in vitro were significantly greater in the h-MSC/r-SMB co-cultures than in those containing r-SMBs only, by real-time PCR and enzyme-linked immunosorbent assay (ELISA). MI was generated by left-coronary artery occlusion in female athymic nude rats. Two weeks later, co-cultured r-SMB or h-MSC cell sheets were implanted or no treatment was performed (n=10 each). Eight weeks later, systolic and diastolic function parameters were improved in all three treatment groups compared to no treatment, with the greatest improvement in the co-cultured cell sheet transplantation group. Consistent results were found for capillary density, collagen accumulation, myocyte hypertrophy, Akt-signaling, STAT3 signaling, and survival of transplanted cells of rat origin, and were related to poly (ADP-ribose) polymerase-dependent signal transduction.Adding MSCs to SMB cell sheets enhanced the sheets' angiogenesis-related paracrine mechanics and, consequently, functional recovery in a rat MI model, suggesting a possible strategy for clinical applications.

  View details for Web of Science ID 000331208800027

  View details for PubMedID 24164292

  View details for PubMedCentralID PMC3926175

• Continuous Flow Left Ventricular Assist Device Implant Significantly Improves Pulmonary Hypertension, Right Ventricular Contractility, and Tricuspid Valve Competence JOURNAL OF CARDIAC SURGERY Atluri, P., Fairman, A. S., MacArthur, J. W., Goldstone, A. B., Cohen, J. E., Howard, J. L., Zalewski, C. M., Shudo, Y., Woo, Y. J. 2013; 28 (6): 770-775

  Abstract

  Continuous flow left ventricular assist devices (CF LVAD) are being implanted with increasing frequency for end-stage heart failure. At the time of LVAD implant, a large proportion of patients have pulmonary hypertension, right ventricular (RV) dysfunction, and tricuspid regurgitation (TR). RV dysfunction and TR can exacerbate renal dysfunction, hepatic dysfunction, coagulopathy, edema, and even prohibit isolated LVAD implant. Repairing TR mandates increased cardiopulmonary bypass time and bicaval cannulation, which should be reserved for the time of orthotopic heart transplantation. We hypothesized that CF LVAD implant would improve pulmonary artery pressures, enhance RV function, and minimize TR, obviating need for surgical tricuspid repair.One hundred fourteen continuous flow LVADs implanted from 2005 through 2011 at a single center, with medical management of functional TR, were retrospectively analyzed. Pulmonary artery pressures were measured immediately prior to and following LVAD implant. RV function and TR were graded according to standard echocardiographic criteria, prior to, immediately following, and long-term following LVAD.There was a significant improvement in post-VAD mean pulmonary arterial pressures (26.6 ± 4.9 vs. 30.2 ± 7.4 mmHg, p = 0.008) with equivalent loading pressures (CVP = 12.0 ± 4.0 vs. 12.1 ± 5.1 p = NS). RV function significantly improved, as noted by right ventricular stroke work index (7.04 ± 2.60 vs. 6.05 ± 2.54, p = 0.02). There was an immediate improvement in TR grade and RV function following LVAD implant, which was sustained long term.Continuous flow LVAD implant improves pulmonary hypertension, RV function, and tricuspid regurgitation. TR may be managed nonoperatively during CF LVAD implant.

  View details for DOI 10.1111/jocs.12214

  View details for Web of Science ID 000326894300051

  View details for PubMedID 24118109

• Sustained release of engineered stromal cell-derived factor 1-a from injectable hydrogels effectively recruits endothelial progenitor cells and preserves ventricular function after myocardial infarction. Circulation Macarthur, J. W., Purcell, B. P., Shudo, Y., Cohen, J. E., Fairman, A., Trubelja, A., Patel, J., Hsiao, P., Yang, E., Lloyd, K., Hiesinger, W., Atluri, P., Burdick, J. A., Woo, Y. J. 2013; 128 (11): S79-86

  Abstract

  Exogenously delivered chemokines have enabled neovasculogenic myocardial repair in models of ischemic cardiomyopathy; however, these molecules have short half-lives in vivo. In this study, we hypothesized that the sustained delivery of a synthetic analog of stromal cell-derived factor 1-α (engineered stromal cell-derived factor analog [ESA]) induces continuous homing of endothelial progenitor cells and improves left ventricular function in a rat model of myocardial infarction.Our previously designed ESA peptide was synthesized by the addition of a fluorophore tag for tracking. Hyaluronic acid was chemically modified with hydroxyethyl methacrylate to form hydrolytically degradable hydrogels through free-radical-initiated crosslinking. ESA was encapsulated in hyaluronic acid hydrogels during gel formation, and then ESA release, along with gel degradation, was monitored for more than 4 weeks in vitro. Chemotactic properties of the eluted ESA were assessed at multiple time points using rat endothelial progenitor cells in a transwell migration assay. Finally, adult male Wistar rats (n=33) underwent permanent ligation of the left anterior descending (LAD) coronary artery, and 100 µL of saline, hydrogel alone, or hydrogel+25 µg ESA was injected into the borderzone. ESA fluorescence was monitored in animals for more than 4 weeks, after which vasculogenic, geometric, and functional parameters were assessed to determine the therapeutic benefit of each treatment group. ESA release was sustained for 4 weeks in vitro, remained active, and enhanced endothelial progenitor cell chemotaxis. In addition, ESA was detected in the rat heart >3 weeks when delivered within the hydrogels and significantly improved vascularity, ventricular geometry, ejection fraction, cardiac output, and contractility compared with controls.We have developed a hydrogel delivery system that sustains the release of a bioactive endothelial progenitor cell chemokine during a 4-week period that preserves ventricular function in a rat model of myocardial infarction.

  View details for DOI 10.1161/CIRCULATIONAHA.112.000343

  View details for PubMedID 24030424

• Spatially oriented, temporally sequential smooth muscle cell-endothelial progenitor cell bi-level cell sheet neovascularizes ischemic myocardium. Circulation Shudo, Y., Cohen, J. E., MacArthur, J. W., Atluri, P., Hsiao, P. F., Yang, E. C., Fairman, A. S., Trubelja, A., Patel, J., Miyagawa, S., Sawa, Y., Woo, Y. J. 2013; 128 (11): S59-68

  Abstract

  Endothelial progenitor cells (EPCs) possess robust therapeutic angiogenic potential, yet may be limited in the capacity to develop into fully mature vasculature. This problem might be exacerbated by the absence of a neovascular foundation, namely pericytes, with simple EPC injection. We hypothesized that coculturing EPCs with smooth muscle cells (SMCs), components of the surrounding vascular wall, in a cell sheet will mimic the native spatial orientation and interaction between EPCs and SMCs to create a supratherapeutic angiogenic construct in a model of ischemic cardiomyopathy.Primary EPCs and SMCs were isolated from Wistar rats. Confluent SMCs topped with confluent EPCs were spontaneously detached from the Upcell dish to create an SMC-EPC bi-level cell sheet. A rodent ischemic cardiomyopathy model was created by ligating the left anterior descending coronary artery. Rats were then immediately divided into 3 groups: cell-sheet transplantation (n=14), cell injection (n=12), and no treatment (n=13). Cocultured EPCs and SMCs stimulated an abundant release of multiple cytokines in vitro. Increased capillary density and improved blood perfusion in the borderzone elucidated the significant in vivo angiogenic potential of this technology. Most interestingly, however, cell fate-tracking experiments demonstrated that the cell-sheet EPCs and SMCs directly migrated into the myocardium and differentiated into elements of newly formed functional vasculature. The robust angiogenic effect of this cell sheet translated to enhanced ventricular function as demonstrated by echocardiography.Spatially arranged EPC-SMC bi-level cell-sheet technology facilitated the natural interaction between EPCs and SMCs, thereby creating structurally mature, functional microvasculature in a rodent ischemic cardiomyopathy model, leading to improved myocardial function.

  View details for DOI 10.1161/CIRCULATIONAHA.112.000293

  View details for PubMedID 24030422

• Normalization of postinfarct biomechanics using a novel tissue-engineered angiogenic construct. Circulation Atluri, P., Trubelja, A., Fairman, A. S., Hsiao, P., MacArthur, J. W., Cohen, J. E., Shudo, Y., Frederick, J. R., Woo, Y. J. 2013; 128 (11): S95-104

  Abstract

  Cell-mediated angiogenic therapy for ischemic heart disease has had disappointing results. The lack of clinical translatability may be secondary to cell death and systemic dispersion with cell injection. We propose a novel tissue-engineered therapy, whereby extracellular matrix scaffold seeded with endothelial progenitor cells (EPCs) can overcome these limitations using an environment in which the cells can thrive, enabling an insult-free myocardial cell delivery to normalize myocardial biomechanics.EPCs were isolated from the long bones of Wistar rat bone marrow. The cells were cultured for 7 days in media or seeded at a density of 5 × 10(6) cells/cm(2) on a collagen/vitronectin matrix. Seeded EPCs underwent ex vivo modification with stromal cell-derived factor-1α (100 ng/mL) to potentiate angiogenic properties and enhance paracrine qualities before construct formation. Scanning electron microscopy and confocal imaging confirmed EPC-matrix adhesion. In vitro vasculogenic potential was assessed by quantifying EPC cell migration and vascular differentiation. There was a marked increase in vasculogenesis in vitro as measured by angiogenesis assay (8 versus 0 vessels/hpf; P=0.004). The construct was then implanted onto ischemic myocardium in a rat model of acute myocardial infarction. Confocal microscopy demonstrated a significant migration of EPCs from the construct to the myocardium, suggesting a direct angiogenic effect. Myocardial biomechanical properties were uniaxially quantified by elastic modulus at 5% to 20% strain. Myocardial elasticity normalized after implant of our tissue-engineered construct (239 kPa versus normal=193, P=0.1; versus infarct=304 kPa, P=0.01).We demonstrate restoration and normalization of post-myocardial infarction ventricular biomechanics after therapy with an angiogenic tissue-engineered EPC construct.

  View details for DOI 10.1161/CIRCULATIONAHA.112.000368

  View details for PubMedID 24030426

• Predicting Right Ventricular Failure in the Modern, Continuous Flow Left Ventricular Assist Device Era 59th Annual Meeting of the Southern-Thoracic-Surgical-Association (STSA) Atluri, P., Goldstone, A. B., Fairman, A. S., MacArthur, J. W., Shudo, Y., Cohen, J. E., Acker, A. L., Hiesinger, W., Howard, J. L., Acker, M. A., Woo, Y. J. ELSEVIER SCIENCE INC. 2013: 857–64

  Abstract

  In the era of destination continuous flow left ventricular assist devices (LVAD), the decision of whether a patient will tolerate isolated LVAD support or will need biventricular support (BIVAD) can be challenging. Incorrect decision making with delayed right ventricular (RV) assist device implantation results in increased morbidity and mortality. Continuous flow LVADs have been shown to decrease pulmonary hypertension and improve RV function. We undertook this study to determine predictors in the continuous flow LVAD era that identify patients who are candidates for isolated LVAD therapy as opposed to biventricular support.We reviewed demographic, hemodynamic, laboratory, and echocardiographic variables for 218 patients who underwent VAD implant from 2003 through 2011 (LVAD=167, BIVAD=51), during the era of continuous flow LVADs.Fifty preoperative risk factors were compared between patients who were successfully managed with an LVAD and those who required a BIVAD. Seventeen variables demonstrated statistical significance by univariate analysis. Multivariable logistic regression analysis identified central venous pressure>15 mmHg (OR 2.0, "C"), severe RV dysfunction (OR 3.7, "R"), preoperative intubation (OR 4.3, "I"), severe tricuspid regurgitation (OR 4.1, "T"), heart rate>100 (OR 2.0, Tachycardia-"T")-CRITT as the major criteria predictive of the need for biventricular support. Utilizing these data, a highly sensitive and easy to use risk score for determining RV failure was generated that outperformed other established risk stratification tools.We present a preoperative risk calculator to determine suitability of a patient for isolated LVAD support in the current continuous flow ventricular assist device era.

  View details for DOI 10.1016/j.athoracsur.2013.03.099

  View details for Web of Science ID 000323940200026

  View details for PubMedID 23791165

• Myocardial Layer-Specific Effect of Myoblast Cell-Sheet Implantation Evaluated by Tissue Strain Imaging CIRCULATION JOURNAL Shudo, Y., Miyagawa, S., Nakatani, S., Fukushima, S., Sakaguchi, T., Saito, A., Asanuma, T., Kawaguchi, N., Matsuura, N., Shimizu, T., Okano, T., Sawa, Y. 2013; 77 (4): 1063-1072

  View details for DOI 10.1253/circj.CJ-12-0615

  View details for Web of Science ID 000318203200035

  View details for PubMedID 23291995

• Mathematically engineered stromal cell-derived factor-1 alpha stem cell cytokine analog enhances mechanical properties of infarcted myocardium JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MacArthur, J. W., Trubelja, A., Shudo, Y., Hsiao, P., Fairman, A. S., Yang, E., Hiesinger, W., Sarver, J. J., Atluri, P., Woo, Y. J. 2013; 145 (1): 278-284

  Abstract

  The biomechanical response to a myocardial infarction consists of ventricular remodeling that leads to dilatation, loss of contractile function, abnormal stress patterns, and ultimately heart failure. We hypothesized that intramyocardial injection of our previously designed pro-angiogenic chemokine, an engineered stromal cell-derived factor-1α analog (ESA), improves mechanical properties of the heart after infarction.Male rats (n = 54) underwent either sham surgery (n = 17) with no coronary artery ligation or ligation of the left anterior descending artery (n = 37). The rats in the myocardial infarction group were then randomized to receive either saline (0.1 mL, n = 18) or ESA (6 μg/kg, n = 19) injected into the myocardium at 4 predetermined spots around the border zone. Echocardiograms were performed preoperatively and before the terminal surgery. After 4 weeks, the hearts were explanted and longitudinally sectioned. Uniaxial tensile testing was completed using an Instron 5543 Microtester. Optical strain was evaluated using custom image acquisition software, Digi-Velpo, and analyzed in MATLAB.Compared with the saline control group at 4 weeks, the ESA-injected hearts had a greater ejection fraction (71.8% ± 9.0% vs 55.3% ± 12.6%, P = .0004), smaller end-diastolic left ventricular internal dimension (0.686 ± 0.110 cm vs 0.763 ± 0.160 cm, P = .04), greater cardiac output (36 ± 11.6 mL/min vs 26.9 ± 7.3 mL/min, P = .05), and a lower tensile modulus (251 ± 56 kPa vs 301 ± 81 kPa, P = .04). The tensile modulus for the sham group was 195 ± 56 kPa, indicating ESA injection results in a less stiff ventricle.Direct injection of ESA alters the biomechanical response to myocardial infarction, improving the mechanical properties in the postinfarct heart.

  View details for DOI 10.1016/j.jtcvs.2012.09.080

  View details for Web of Science ID 000312386300047

  View details for PubMedID 23244259

• Mitral Valve Repair for Medically Refractory Functional Mitral Regurgitation in Patients With End-Stage Renal Disease and Advanced Heart Failure CIRCULATION Kainuma, S., Taniguchi, K., Daimon, T., Sakaguchi, T., Funatsu, T., Miyagawa, S., Kondoh, H., Takeda, K., Shudo, Y., Masai, T., Ohishi, M., Sawa, Y. 2012; 126 (11): S205-S213

  Abstract

  Information regarding patient selection for mitral valve repair for chronic kidney disease or end-stage renal disease (ESRD) with severe heart failure (HF) as well as outcome is limited.We classified 208 patients with advanced HF symptoms (Stage C/D) undergoing mitral valve repair for functional mitral regurgitation into 3 groups: estimated glomerular filtration rate ≥30 mL/min/1.73 m(2) (control group, n=144); estimated glomerular filtration rate <30 mL/min/1.73 m(2), not dependent on hemodialysis (late chronic kidney disease group, n=45), and ESRD on hemodialysis (ESRD group, n=19; preoperative hemodialysis duration 83 ± 92 months). Follow-up was completed with a mean duration of 49 ± 25 months. Postoperative (1-month) cardiac catheterization showed that left ventricular end-systolic volume index decreased from 109 ± 38 to 79 ± 41, 103 ± 31 to 81 ± 31, and 123 ± 40 to 76 ± 34 mL/m(2), in the control, late chronic kidney disease, and ESRD groups, respectively. Left ventricular end-diastolic pressure decreased, whereas cardiac index increased in all groups with no intergroup differences for those postoperative values. Freedom from mortality and HF readmission at 5 years was 18% ± 7% in late chronic kidney disease (P<0.0001 versus control, P=0.01 versus ESRD), and 64% ± 12% in ESRD (P=1 versus control) as compared with 52% ± 5% in the control group (median event-free survival, 26, 67, and 63 months, respectively).Mitral valve repair for medically refractory functional mitral regurgitation in patients with advanced HF yielded improvements in left ventricular function and hemodynamics irrespective of preoperative renal function status. Patients with ESRD showed favorable late outcome in terms of freedom from mortality and readmission for HF as compared with those with late chronic kidney disease. Further studies are needed to assess the survival benefits of mitral valve repair in patients with ESRD and advanced HF.

  View details for DOI 10.1161/CIRCULATIONAHA.111.077768

  View details for Web of Science ID 000314150200029

  View details for PubMedID 22965985

• Serial multidetector computed tomography assessment of left ventricular reverse remodeling, mass, and regional wall stress after restrictive mitral annuloplasty in dilated cardiomyopathy JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Shudo, Y., Taniguchi, K., Takeda, K., Sakaguchi, T., Funatsu, T., Kondoh, H., Sawa, Y. 2012; 143 (4): S43-S47

  Abstract

  To evaluate serial data on left ventricular and myocardial reverse remodeling after restrictive mitral annuloplasty.Thirteen patients (age, 64 ± 6 years) with functional mitral regurgitation associated with dilated cardiomyopathy (ejection fraction, ≤ 35%) were examined before (baseline), soon (1.7 ± 1.5 months), and more than 1 year (16 ± 8 months) after restrictive mitral annuloplasty using multidetector computed tomography. The left ventricular end-diastolic and end-systolic volume indexes, left ventricular ejection fraction, left ventricular mass index, and end-systolic wall stress were estimated.In the period soon after restrictive mitral annuloplasty, significant reverse left ventricular remodeling was present, with decreases in the left ventricular end-diastolic volume index (149 ± 42 to 119 ± 41 mL/m(2), P = .04) and left ventricular end-systolic volume index (114 ± 44 to 78 ± 43 mL/m(2), P = .02), and an increase in left ventricular ejection fraction (25% ± 10% to 37% ± 14%, P = .01). Additional changes in these parameters were seen in the later period (103 ± 29 mL/m(2), 61 ± 23 mL/m(2), and 42% ± 9%, respectively; all P < .05 vs baseline). In the early postrestrictive mitral annuloplasty period, the left ventricular mass index did not change significantly (104 ± 22 to 104 ± 18 g/m(2), P = NS), but significant regression occurred in the later period (90 ± 17 g/m(2), P < .05 vs baseline). The end-systolic wall stress was significantly decreased in the early period (P < .05) and was sustained in the late period. Furthermore, the increase in left ventricular ejection fraction in the late period correlated significantly with the magnitude of the end-systolic wall stress reduction (r = -0.67, P = .01).Our findings indicate that ventricular reverse remodeling occurs soon after restrictive mitral annuloplasty. In contrast, myocardial reverse remodeling (ie, regression of myocardial hypertrophy) occurs over time between the early and late postoperative periods. Our data also suggest that the late improvement in left ventricular systolic performance might be attributable to a decrease in the left ventricular afterload.

  View details for DOI 10.1016/j.jtcvs.2011.11.013

  View details for Web of Science ID 000301598700011

  View details for PubMedID 22169453

• Left Ventricular Mechanics Following Restrictive Mitral Annuloplasty for Functional Mitral Regurgitation: Two-Dimensional Speckle Tracking Echocardiographic Study ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES Shudo, Y., Nakatani, S., Sakaguchi, T., Miyagawa, S., Yoshikawa, Y., Takeda, K., Saito, S., Takeda, Y., Sakata, Y., Yamamoto, K., Sawa, Y. 2012; 29 (4): 445-450

  Abstract

  Restrictive mitral annuloplasty (RMA) is widely employed for patients with functional mitral regurgitation (MR). Its improvement of left ventricular (LV) function has been demonstrated by only a gradual increase in LV ejection fraction (EF) in the chronic phase. However, the detailed evaluation of changes in LV function has not been fully elucidated in functional MR patients before and after RMA. Therefore, we performed two-dimensional speckle tracking echocardiography (2D-STE), which enables accurate evaluation of myocardial deformation and rotation that are undetectable by conventional echocardiography.We studied 13 patients (mean age 61 ± 10 years) with functional MR associated with cardiomyopathy undergoing RMA. In addition to conventional echocardiographic measurements, 2D-STE was performed to measure peak systolic radial (RS), circumferential (CS), and longitudinal (LS) strains and twist before and 4 ± 2 weeks after surgery. LV twist was defined as the difference between the apical and basal rotations.After RMA, EF and LS remained unchanged, but RS and CS were significantly improved at the mid-LV (RS, 20.6 ± 10.8 vs 24.5 ± 11.6%; CS, -9.6 ± 5.2 vs -12.8 ± 5.6%) and at the apex (RS, 15.0 ± 12.2 vs 18.7 ± 8.6%; CS, -4.4 ± 3.0 vs -7.8 ± 4.8%). RS and CS were unchanged at the base. The apical and basal rotations changed significantly, from 3.5°± 0.7° to 9.2°± 2.1°, and -2.1°± 0.7° to -3.8°± 1.0°, respectively. Consequently, the LV twist increased significantly, from 5.6°± 1.0° to 13.0°± 1.9°.Radial and circumferential strains and LV twist increased significantly in the early postoperative period in functional MR patients after RMA and concomitant procedures.

  View details for DOI 10.1111/j.1540-8175.2011.01607.x

  View details for Web of Science ID 000302540700019

  View details for PubMedID 22486374

• The extent of early left ventricular reverse remodelling is related to midterm outcomes after restrictive mitral annuloplasty in patients with non-ischaemic dilated cardiomyopathy and functional mitral regurgitation EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Takeda, K., Sakaguchi, T., Miyagawa, S., Shudo, Y., Kainuma, S., Masai, T., Taniguchi, K., Sawa, Y. 2012; 41 (3): 506-511

  Abstract

  Restrictive mitral annuloplasty (RMA) can often improve heart failure symptoms and induce left ventricular (LV) reverse remodelling in patients with non-ischaemic dilated cardiomyopathy (DCM) and functional mitral regurgitation. However, it is unknown whether the observed LV reverse remodelling translates into better outcomes or not.Fifty patients with advanced non-ischaemic DCM (age, 64 ± 10 years, 74% men) underwent RMA and were followed up with a mean of 2 years. Preoperatively, all had 3 to 4+ functional mitral regurgitation (MR), an ejection fraction (EF) of 26 ± 8.6 %, an indexed LV end-systolic volume (LVESVI) of 112 ± 47 ml/m(2). All patients received complete semi-rigid undersized ring annuloplasty. Correlations between early reduction in LVESVI at 1 month after the operation and mid-term clinical outcomes were analysed.There was no 30-day mortality. LVESVI significantly decreased to 96 ± 53 ml/m(2) and LVEF improved to 31 ± 15%. During follow-up, 16 (32%) recurred heart failure, of whom 7 (14%) died. The receiver operating characteristic (ROC) curve found that a reduction in LVESVI >8.3% had a sensitivity of 80% and a specificity of 78% in predicting all adverse events. With this cut-off value, there were 30 (60%) responders to reverse remodelling. Responders had significantly better survival (96.4 versus 68.7%, P = 0.007) and freedom from heart failure rate (85.4 versus 31.8%, P = 0.0003) than non-responders at 3 years. In a 1-year follow-up echocardiographic study, non-responders had shown no significant LV reverse remodelling with greater degree of residual MR than responders.The extent of early LV reverse remodelling is related to mid-term mortality, heart failure events and late reverse remodelling and repair durability after RMA for non-ischaemic DCM.

  View details for DOI 10.1093/ejcts/ezr004

  View details for Web of Science ID 000300507400017

  View details for PubMedID 22011774

• Novel regenerative therapy using cell-sheet covered with omentum flap delivers a huge number of cells in a porcine myocardial infarction model JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Shudo, Y., Miyagawa, S., Fukushima, S., Saito, A., Shimizu, T., Okano, T., Sawa, Y. 2011; 142 (5): 1188-1196

  Abstract

  A key challenge to applying cell transplantation to treat severely damaged myocardium is in delivering large numbers of cells with minimum cell loss. We developed a new implantation method using skeletal myoblast (SMB) sheets, wrapped with an omentum flap as a blood supply to deliver huge numbers of SMBs to the damaged heart. We examined whether this method could be used to deliver a large amount of cells to deteriorated porcine myocardium.Cell sheets were obtained by culturing mini-pig autologous SMB cells on temperature-responsive culture dishes. Myocardial infarction was induced by placing an ameroid constrictor around the left anterior descending artery. The mini-pigs were divided into 4 treatment groups (n = 6 in each): cell sheets with omentum, cell sheets only, omentum only, and sham operation. Each animal implant consisted of 30 cell sheets (1.5 × 10(7) cells per sheet). Six 5-layer constructs were each placed on a different area, immediately adjacent to but not overlapping one another, to cover the infarct and border regions.The new regenerative cell delivery system using SMB sheets covered and wrapped with omentum resulted in (1) a significantly reduced infarct size causing, at least in part, a thin scar with thick well-vascularized cardiac tissue; (2) increased angiogenesis, as determined by a significantly higher vascular density; and (3) improved cardiac function, as determined by echocardiography, compared with the conventional method (SMB sheet implantation).This cell delivery system shows potential for repairing the severely failed heart.

  View details for DOI 10.1016/j.jtcvs.2011.07.002

  View details for Web of Science ID 000296337500035

  View details for PubMedID 21924436

• Establishing New Porcine Ischemic Cardiomyopathy Model by Transcatheter Ischemia-Reperfusion of the Entire Left Coronary Artery System for Preclinical Experimental Studies TRANSPLANTATION Shudo, Y., Miyagawa, S., Fukushima, S., Saito, A., Kawaguchi, N., Matsuura, N., Sawa, Y. 2011; 92 (7): E34-E35

  View details for DOI 10.1097/TP.0b013e31822d875c

  View details for Web of Science ID 000295319500003

  View details for PubMedID 21952307

• Does Stringent Restrictive Annuloplasty for Functional Mitral Regurgitation Cause Functional Mitral Stenosis and Pulmonary Hypertension? CIRCULATION Kainuma, S., Taniguchi, K., Daimon, T., Sakaguchi, T., Funatsu, T., Kondoh, H., Miyagawa, S., Takeda, K., Shudo, Y., Masai, T., Fujita, S., Nishino, M., Sawa, Y. 2011; 124 (11): S97-S106

  Abstract

  It remains controversial whether restrictive mitral annuloplasty (RMA) for functional mitral regurgitation (MR) can induce functional mitral stenosis (MS) that may cause postoperative residual pulmonary hypertension (PH).One hundred eight patients with left ventricular (LV) dysfunction and severe MR underwent RMA with stringent downsizing of the mitral annulus. Systolic pulmonary artery pressure (PAP) and mitral valve performance variables were determined by Doppler echocardiography prospectively and 1 month after RMA. Fifty-eight patients underwent postoperative hemodynamic measurements. Postoperative echocardiography showed a mean pressure half-time of 92 ± 14 ms, a transmitral mean gradient of 2.9 ± 1.1 mm Hg, and a mitral valve effective orifice area of 2.4 ± 0.4 cm(2), consistent with functional MS. Doppler-derived systolic PAP was 32 ± 8 mm Hg, which correlated weakly with the transmitral mean gradient (ρ=0.23, P=0.02). Postoperative cardiac catheterization also showed significant improvements in LV volume and systolic function, pulmonary capillary wedge pressure, cardiac index, and systolic PAP; the latter was associated with LV end-diastolic pressure [standardized partial regression coefficient (SPRC)=0.51], pulmonary vascular resistance (SPRC=0.47), cardiac index (SPRC=0.37), and transmitral pressure gradient (SPRC=0.20). In a multivariate Cox proportional hazard model, postoperative PH (systolic PAP >40 mm Hg), but not mitral valve performance variables, was strongly associated with adverse cardiac events.RMA for functional MR resulted in varying degrees of functional MS. However, our data were more consistent with the residual PH being caused by LV dysfunction and pulmonary vascular disease than by the functional MS. The residual PH, not functional MS, was the major predictor of post-RMA adverse cardiac events.

  View details for DOI 10.1161/CIRCULATIONAHA.110.013037

  View details for Web of Science ID 000294782800012

  View details for PubMedID 21911824

• Restrictive Mitral Annuloplasty With or Without Surgical Ventricular Restoration in Ischemic Dilated Cardiomyopathy With Severe Mitral Regurgitation CIRCULATION Shudo, Y., Taniguchi, K., Takeda, K., Sakaguchi, T., Funatsu, T., Matsue, H., Miyagawa, S., Kondoh, H., Kainuma, S., Kubo, K., Hamada, S., Izutani, H., Sawa, Y. 2011; 124 (11): S107-S114

  Abstract

  We assessed changes in left ventricular (LV) volume and function and in regional myocardial wall stress in noninfarcted segments after restrictive mitral annuloplasty (RMA) with or without surgical ventricular restoration (SVR).Thirty-nine patients with ischemic cardiomyopathy (ejection fraction ≤ 0.35) and severe mitral regurgitation (≥ 3) were studied before and 2.8 months after surgery with cine-angiographic multidetector computed tomography (cine-MDCT). Eighteen underwent RMA alone (RMA group) and 21 underwent RMA and SVR (RMA+SVR group). In addition to measuring conventional parameters (LV end-diastolic volume index [LVEDVI], LV end-systolic volume index [LVESVI], and LV ejection fraction), we evaluated the regional circumferential end-systolic wall stress and mean circumferential fiber shortening in both the basal and mid-LV regions using 3-dimensional cine-MDCT images. LV end-diastolic and end-systolic volume indexes were significantly greater in the RMA+SVR group than in the RMA group preoperatively, but these values did not differ significantly postoperatively. LV end-diastolic and end-systolic volume indexes decreased significantly, by 21% and 27% after RMA and by 35% and 42% after RMA and SVR, and the percent reductions in LV end-diastolic and end-systolic volume indexes were significantly larger in the RMA+SVR group. Regional end-systolic wall stress decreased and circumferential fiber shortening increased significantly in the noninfarcted regions after RMA with or without SVR.RMA plus SVR showed a potentially greater reduction of LV end-diastolic and end-systolic volume indexes than RMA alone. In selected patients with more advanced LV remodeling, concomitant SVR may favorably affect the LV reverse-remodeling process induced by RMA.

  View details for DOI 10.1161/CIRCULATIONAHA.110.010330

  View details for Web of Science ID 000294782800013

  View details for PubMedID 21911799

• Novel software package for quantifying local circumferential myocardial stress INTERNATIONAL JOURNAL OF CARDIOLOGY Shudo, Y., Matsumiya, G., Takeda, K., Matsue, H., Taniguchi, K., Sawa, Y. 2011; 147 (1): 134-136

  Abstract

  Local myocardial stress is an important index of ventricular loading conditions. We developed a novel software package to provide estimation of local circumferential stress in the entire left ventricle (LV) based on Janz's method using contemporary LV imaging techniques. The aim of this study was to confirm the validity of our novel software by comparing local circumferential stress (local σ) with global equatorial stress (global σ) values. We acquired 30° right anterior oblique LVG images in 74 patients (aortic regurgitation; n = 48, aortic stenosis; n = 26) and 26 healthy subjects, then analyzed them using Janz's method to elucidate local σ in segment #12 (mid-anterolateral) based on AHA/ASE segmentation criteria. Global σ was obtained using Mirsky's formula. A highly significant correlation was found between local σ and global σ (r = 0.99, p < 0.001). Bland-Altman analysis also showed good agreement between the two methods (mean bias 2.4 kdyn/cm(2), limits of agreement 9.3 kdyn/cm(2)/-4.6 kdyn/cm(2)). There were good correlations for both intra-observer and inter-observer agreement. Our novel software package was shown useful to assess local circumferential stress with contemporary cardiovascular imaging techniques.

  View details for DOI 10.1016/j.ijcard.2009.05.026

  View details for Web of Science ID 000287443300027

  View details for PubMedID 20064671

• Resection of advanced stage malignant retroperitoneal neoplasms with tumor thrombus extending into the right atrium: Report of four cases SURGERY TODAY Shudo, Y., Matsumiya, G., Sakaguchi, T., Fujita, T., Yamauchi, T., Sawa, Y. 2011; 41 (2): 262-265

  Abstract

  Surgery for retroperitoneal neoplasms with a tumor thrombus extension into the right atrium is challenging. This study reviewed four surgical cases of advanced stage malignant neoplasms with the tumor thrombus extending into the right atrium. The malignant neoplasms involved the kidney in two patients, and the liver and adrenal gland in one each. The tumor thrombus was removed through a longitudinal cavotomy and right atriotomy in all cases. The inferior vena cava reconstruction was performed by directly closing it in one patient and by pericardial patch suturing in another. Cardiopulmonary bypass was used for all procedures and a Pringle maneuver was used to reduce bleeding from the liver in three. There was no perioperative or hospital death. Two of the four with renal cell carcinoma were alive 7 and 13 months after the surgery. One with hepatocellular carcinoma died of recurrent malignancy after 4 months, while the patient with an adrenal carcinoma remained disease free after surgery. These cases indicate the safety of the present procedure. Although the long-term results are still unknown, there were favorable early results and a lack of perioperative complications. Surgical challenges in resecting an intracardiac extension of retroperitoneal malignancy require close cooperation among the attending urologist, and both gastrointestinal and cardiovascular surgeons.

  View details for DOI 10.1007/s00595-009-4231-2

  View details for Web of Science ID 000286600400018

  View details for PubMedID 21264766

• Assessment of Changes in Mitral Valve Configuration With Multidetector Computed Tomography Impact of Papillary Muscle Imbrication and Ring Annuloplasty CIRCULATION Shudo, Y., Matsumiya, G., Sakaguchi, T., Miyagawa, S., Yoshikawa, Y., Yamauchi, T., Takeda, K., Saito, S., Nakatani, S., Taniguchi, K., Izutani, H., Sawa, Y. 2010; 122 (11): S29-S36

  Abstract

  The optimal surgical procedures in functional mitral regurgitation remain controversial. We applied papillary muscle imbrication (PMI) combined with undersized mitral annuloplasty (UMAP). Multidetector computed tomography (MDCT) provides images of different phases of the cardiac cycle, allowing an assessment of the geometry. In the present study, we evaluated the mitral valve configuration and subvalvular apparatus before and after UMAP and/or PMI using MDCT imaging.We studied 26 patients with functional mitral regurgitation (3+ to 4+) with an ejection fraction ≥35% who underwent diagnostic MDCT examinations before and early after the operation. Of these, 15 underwent UMAP and PMI (UMAP+PMI group) and 11 underwent UMAP (UMAP group). The annular anteroposterior diameter, tenting height, tenting area, and interpapillary muscle distance at end-systole were quantified. The annular anteroposterior diameter, tenting height, and tenting area were significantly decreased after the operation in both groups. Whereas the average change in annular anteroposterior diameter, tenting area, and interpapillary muscle distance did not differ between the 2 groups, the average change in tenting height was greater in the UMAP+PMI group than in the UMAP group (5.1±1.3 versus 3.8±2.3 mm, P=0.036). There was a significant correlation between the change in interpapillary muscle distance and the change in tenting height in the UMAP+PMI group (r=0.788, P=0.0005).Our results examined with MDCT indicated that UMAP combined with PMI improved leaflet tethering compared with UMAP, reflecting differences in the effects of the surgical procedures used, and suggested that concomitant PMI might be beneficial in some cases.

  View details for DOI 10.1161/CIRCULATIONAHA.109.928002

  View details for Web of Science ID 000282294800005

  View details for PubMedID 20837921

• Mechanism of Beneficial Effects of Restrictive Mitral Annuloplasty in Patients With Dilated Cardiomyopathy and Functional Mitral Regurgitation CIRCULATION Takeda, K., Taniguchi, K., Shudo, Y., Kainuma, S., Hamada, S., Matsue, H., Matsumiya, G., Sawa, Y. 2010; 122 (11): S3-S9

  Abstract

  Restrictive mitral annuloplasty (RMA) often leads to reverse left ventricular (LV) remodeling in patients with advanced cardiomyopathy and functional mitral regurgitation. However, the mechanism responsible for its favorable effects on LV ejection performance has been poorly understood. We evaluated systolic wall stress using cineangiographic multidetector computed tomography (MDCT) and our developed software system to assess stress-shortening relations before and after RMA.Twenty-four patients with dilated cardiomyopathy underwent 64-row MDCT before and 2 months after RMA. All patients underwent stringent downsizing annuloplasty with a semirigid complete ring. Reconstructed images were used to calculate LV end-diastolic index (EDVI) and end-systolic volume index (ESVI), LV ejection fraction, and regional and global end-systolic wall stress (ESS). After RMA, LVEDVI and LVESVI decreased from 151±52 to 131±53 mL/m(2) (P=0.0001) and from 114±48 to 92±50 mL/m(2) (P=0.0001), respectively. Global ESS decreased from 157±43 to 139±50 kdyne/cm(2) (P=0.01), and LV ejection fraction improved from 27±8.0 to 33±13% (P=0.0007). There were significant correlations between change in LVEDVI and LVESVI (r=0.88, P<0.0001) and change in LVESVI and global ESS (r=0.68, P=0.0002). Moreover, the magnitude of increase in LV ejection fraction significantly correlated with the degree of reduction in global ESS (r=-0.61, P=0.002). Patients without significant reverse LV remodeling had significantly higher preoperative and postoperative global ESS than those with it.Our study suggests that decrease in afterload after reduction in volume overload was responsible for postoperative reverse LV remodeling process after RMA.

  View details for DOI 10.1161/CIRCULATIONAHA.109.927855

  View details for Web of Science ID 000282294800001

  View details for PubMedID 20837922

• A Simplified Echocardiographic Measurements of Direct Effects of Restrictive Annuloplasty on Mitral Valve Geometry ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES Shudo, Y., Matsue, H., Toda, K., Hata, H., Fujita, S., Taniguchi, K., Sawa, Y. 2010; 27 (8): 931-936

  Abstract

  The purpose of this study was to evaluate the direct effects of restrictive mitral annuloplasty on mitral valve geometry.We studied 23 patients (mean age: 63 ± 5 years) with functional mitral regurgitation (moderate to severe) and advanced cardiomyopathy (ejection fraction: 25 ± 8%) with ischemic (n = 15) or nonischemic (n = 8) conditions, who underwent restrictive annuloplasty. We determined annular septal-lateral diameter, tenting height, tenting area, vertical length of coaptation of the mitral leaflets (coaptation length), and ratio of coaptation length to septal-lateral diameter (coaptation length index) at end-systole, before and after surgery, using transthoracic echocardiography.Annular septal-lateral diameter, tenting height, and tenting area were significantly decreased (34 ± 7 to 20 ± 5 mm, P < 0.05; 9 ± 4 to 5 ± 2 mm, P < 0.05; 210 ± 120 to 80 ± 50 mm(2) , P < 0.05, respectively), whereas coaptation length and coaptation length index were significantly increased (3.4 ± 1.3 to 6.5 ± 2.9 mm, P < 0.05; 0.11 ± 0.06 to 0.33 ± 0.15, P < 0.05, respectively). Spearman's rank correlation analysis revealed that these five variables had a statistically significant correlation with the degree of mitral regurgitation. Furthermore, stepwise regression analysis showed that coaptation length index, in contrast to coaptation length, was the most important correlate with the degree of mitral regurgitation.Our simplified parameters were useful for quantitative and geometrical descriptions of mitral valve geometry, and may also provide important information for developing a surgical strategy for functional mitral regurgitation.

  View details for DOI 10.1111/j.1540-8175.2010.01182.x

  View details for Web of Science ID 000281900100012

  View details for PubMedID 20849480

• Impact of surgical ventricular reconstruction for ischemic dilated cardiomyopathy on restrictive filling pattern. General thoracic and cardiovascular surgery Shudo, Y., Matsumiya, G., Sakaguchi, T., Miyagawa, S., Yamauchi, T., Takeda, K., Saito, S., Taniguchi, K., Sawa, Y. 2010; 58 (8): 399-404

  Abstract

  Little information related to the effects of surgical ventricular reconstruction on left ventricular diastolic function is available. The aims of this study were to examine the effects of surgical ventricular reconstruction on left ventricular diastolic function and assess the predictive significance of that function on clinical outcome in patients with ischemic cardiomyopathy due to broad anteroseptal myocardial infarction undergoing surgical ventricular reconstruction.We studied 21 patients undergoing surgical ventricular reconstruction and combined surgery for ischemic cardiomyopathy with a low ejection fraction (mean ejection fraction 23% +/- 6%). Doppler echocardiography was performed before and 6 +/- 4 months after the operation.There were no deaths within 30 days. Of the 21 patients, 6 reached the clinical endpoint (cardiac death or hospitalization due to congestive heart failure). The Doppler-derived restrictive filling pattern--defined as the deceleration time (DcT) <140 ms and the mitral peak early/mitral late diastolic filling velocity (E/A) ratio >1.5--was significantly related to reaching the clinical endpoint (P < 0.01). Furthermore, stepwise multivariate analysis showed that a preoperative restrictive filling pattern was the only independent predictor of reaching the clinical endpoint (P < 0.005, F = 11.2).In patients with ischemic cardiomyopathy undergoing surgical ventricular reconstruction and combined surgery, surgical ventricular reconstruction did not change the restrictive filling pattern, and the preoperative restrictive filling pattern was an important marker of postoperative clinical outcome.

  View details for DOI 10.1007/s11748-010-0597-8

  View details for PubMedID 20703860

• Assessment of regional myocardial wall stress before and after surgical correction of functional ischaemic mitral regurgitation using multidetector computed tomography and novel software system EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Shudo, Y., Taniguchi, K., Takeda, K., Sakaguchi, T., Matsue, H., Izutani, H., Matsumiya, G., Sawa, Y. 2010; 38 (2): 163-169

  Abstract

  The objective of this study was to assess changes in left ventricular (LV) volume, function and regional myocardial wall stress in non-infarcted segments following restrictive mitral annuloplasty (RMA) in patients with ischaemic cardiomyopathy (ICM) and severe functional mitral regurgitation (MR).Twenty-two patients with ICM (ejection fraction <35%) and severe MR were investigated before and 3 months after RMA using cine-angiographic multidetector row computed tomography (cine-MDCT). For comparative purposes, 38 normal subjects were also studied. Cine-MDCT LV images were reconstructed in a cardiac cycle and regional circumferential wall stress (end-systolic stress (ESS)) was evaluated from the LV end-systolic image using Janz's method. The ESS was determined in six basal and six mid-LV segments of the ventricle based on AHA/ASE criteria. Five apical infarcted segments were not analysed. Mean circumferential fibre shortening (CFS) in both basal and mid-LV regions was determined as a parameter of regional systolic performance.Left ventricular end-diastolic volume (index) (LVEDVI) and left ventricular end-systolic volume (index) (LVESVI) decreased significantly and left ventricular ejection fraction (LVEF) increased after surgery. Neither end-systolic nor end-diastolic sphericity index changed significantly after surgery. Regional ESS significantly decreased in both basal and mid-LV regions after surgery. There was a significant inverse correlation between the change in average value of regional ESS and magnitude of increase in mean CFS of the mid-LV region (r=-0.67, p=0.0018). Postoperative reduction in ESS in the mid-LV region was also correlated with improvement in global EF (r=-0.72, p<0.01).The present cine-MDCT may be useful for assessing regional myocardial stress in patients with ICM. We found that RMA could reduce both end-diastolic and end-systolic volume leading to reduction in regional systolic wall stress, which resulted in improved ejection performance of non-infarcted myocardium in patients with functional MR and ICM.

  View details for DOI 10.1016/j.ejcts.2010.01.029

  View details for Web of Science ID 000280941200010

  View details for PubMedID 20619218

• Cardiomyoblast-like Cells Differentiated from Human Adipose Tissue-Derived Mesenchymal Stem Cells Improve Left Ventricular Dysfunction and Survival in a Rat Myocardial Infarction Model TISSUE ENGINEERING PART C-METHODS Okura, H., Matsuyama, A., Lee, C., Saga, A., Kakuta-Yamamoto, A., Nagao, A., Sougawa, N., Sekiya, N., Takekita, K., Shudo, Y., Miyagawa, S., Komoda, H., Okano, T., Sawa, Y. 2010; 16 (3): 417-425

  Abstract

  Adipose tissue-derived mesenchymal stem cells (ADMSCs) are multipotent cells. Here we examined whether human ADMSCs (hADMSCs) could differentiate into cardiomyoblast-like cells (CLCs) by induction with dimethylsulfoxide and whether the cells would be utilized to treat cardiac dysfunction. Dimethylsulfoxide induced the expression of various cardiac markers in hADMSCs, such as alpha-cardiac actin, cardiac myosin light chain, and myosin heavy chain; none of which were detected in noncommitted hADMSCs. The induced cells were thus designated as hADMSC-derived CLCs (hCLCs). To confirm their beneficial effect on cardiac function, hCLC patches were transplanted onto the Nude rat myocardial infarction model, and compared with noncommitted hADMSC patch transplants and sham operations. Echocardiography demonstrated significant short-term improvement of cardiac function in both the patch-transplanted groups. However, long-term follow-up showed rescue and maintenance of cardiac function in the hCLC patch-transplanted group only, but not in the noncommitted hADMSC patch-transplanted animals. The hCLCs, but not the hADMSCs, engrafted into the scarred myocardium and differentiated into human cardiac troponin I-positive cells, and thus regarded as cardiomyocytes. Transplantation of the hCLC patches also resulted in recovery of cardiac function and improvement of long-term survival rate. Thus, transplantation of hCLC patches is a potentially effective therapeutic strategy for future cardiac tissue regeneration.

  View details for DOI 10.1089/ten.tec.2009.0362

  View details for Web of Science ID 000278083900010

  View details for PubMedID 19624256

• Impact of untreated mild-to-moderate mitral regurgitation at the time of isolated aortic valve replacement on late adverse outcomes EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Takeda, K., Matsumiya, G., Sakaguchi, T., Miyagawa, S., Yamauchi, T., Shudo, Y., Izutani, H., Sawa, Y. 2010; 37 (5): 1033-1038

  Abstract

  The impact of untreated mild-to-moderate mitral regurgitation (MR) on patients undergoing isolated aortic valve replacement (AVR) is uncertain. The aim of this study is to investigate its long-term effects on outcomes.We retrospectively reviewed 193 consecutive patients undergoing isolated AVR between 1993 and 2007. The mean age of the study group was 64+/-12 years, 59% were male and the mean preoperative ejection fraction was 59+/-12%. The pathologic aetiology and degree of MR was determined on preoperative echocardiogram. Patients were stratified into preoperative no/trivial MR (group I; n=134) versus mild-to-moderate MR (group II; n=59). The aetiology of MR in group II was either organic (n=35, 60%) or functional (n=24, 41%). Survival and functional outcome were compared between the two groups and analyses for predictors of adverse events were performed by the Cox proportional hazard model.Operative mortality was 2.6% (n=5). In group II, mean degree of MR significantly decreased from 2.1+/-0.3 to 1.6+/-0.8 during the late period (p=0.003). The improvement in MR grade was more obvious in patients with functional aetiology. Although the actuarial survival was not significantly different between groups, freedom from re-admission for heart failure at 10 years was significantly lower in group II than in group I (23% vs 83%; p=0.002). Multivariate analysis demonstrated that independent predictors of heart failure were presence of mild-to-moderate MR (p=0.012, odds ratio (OR) 3.8) and left ventricular ejection fraction (p=0.004, OR 0.95).Despite the significant reduction after isolated AVR, preoperative mild-to-moderate MR is an independent risk factor impacting long-term functional outcome. Our results suggested that the concomitant mitral valve surgery for mild-to-moderate MR is warranted, especially in patients with reduced left ventricular function.

  View details for DOI 10.1016/j.ejcts.2009.11.046

  View details for Web of Science ID 000278614000008

  View details for PubMedID 20362456

• Redo Arch Aneurysm Repair for New-Onset Aortic Arch Dissection Following Ascending Aortic Surgery: Long Elephant Trunk Technique Combined With Trifurcate-Branched Graft ANNALS OF VASCULAR SURGERY Shudo, Y., Toda, K., Matsue, H., Hata, H., Yoshida, K., Taniguchi, K. 2010; 24 (3)

  Abstract

  Reoperative surgical intervention for a new-onset aortic arch dissection following a Bentall procedure or graft replacement for the ascending aorta is often difficult, especially in elderly patients. Herein, we report a re-do arch replacement method using a trifurcate-branched graft and long elephant trunk anastomosis at the composite root graft on the ascending aorta. The present technique is feasible as an alternative for new-onset or residual aortic arch aneurysm, as well as dissection following an operation for the ascending aorta.

  View details for DOI 10.1016/j.avsg.2009.05.017

  View details for Web of Science ID 000275516100021

  View details for PubMedID 20053528

• Repair for acute type A aortic dissection with a long elephant trunk technique JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Hata, H., Toda, K., Shudo, Y., Kainuma, S., Yoshida, K., Yamamoto, K., Taniguchi, K. 2009; 137 (3): 777-778

  View details for DOI 10.1016/j.jtcvs.2008.07.058

  View details for Web of Science ID 000263791500052

  View details for PubMedID 19258117

• Elephant trunk anastomosis proximal to origin of innominate artery in total arch replacement ANNALS OF THORACIC SURGERY Taniguchi, K., Toda, K., Hata, H., Shudo, Y., Matsue, H., Takahashi, T., Kuki, S. 2007; 84 (5): 1729-1734

  Abstract

  The purpose of this study was to describe our current technique for aortic arch replacement using a four-branched arch graft and a long elephant trunk.Using our method, the ascending aorta is replaced with a four-branched Hemashield arch graft (Hemashield Platinum, Woven Double Velour [Boston Scientific Corp, Wayne, NJ]) while cooling the patient. When 25 degrees C is reached, selective cerebral perfusion is started and the elephant trunk is inserted under open distal conditions into the descending aorta using a catching catheter introduced through a femoral artery. A distal aortic anastomosis is then performed between the four-branched graft and distal aorta incorporating the elephant trunk at the base of the innominate artery. Arch vessels are reconstructed separately during rewarming.Between October 1998 and December 2005, we performed the present technique in 52 patients with no operative deaths within 30 days after the procedure. The mean duration of hypothermic circulatory arrest was 24 +/- 5 minutes, whereas that of selective cerebral perfusion was 86 +/- 9 minutes.The technique described herein requires a shorter circulatory arrest time and is uniformly applicable to patients with extensive thoracic aortic aneurysms.

  View details for DOI 10.1016/j.athoracsur.2007.05.087

  View details for Web of Science ID 000250782500045

  View details for PubMedID 17954096

• Detection of novel serotype K Streptococcus mutans in infective endocarditis patients JOURNAL OF MEDICAL MICROBIOLOGY Nakano, K., Nomura, R., Nemoto, H., Murai, T., Yoshioka, H., Shudo, Y., Hata, H., Toda, K., Taniguchi, K., Amano, A., Ooshima, T. 2007; 56 (10): 1413-1415

  View details for Web of Science ID 000250538100026

  View details for PubMedID 17893184

• Left ventricular mass: impact on left ventricular contractile function and its reversibility in patients undergoing aortic valve replacement EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Taniguchi, K., Takahashi, T., Toda, K., Matsue, H., Shudo, Y., Shintani, H., Mitsuno, M., Sawa, Y. 2007; 32 (4): 588-595

  Abstract

  We examined the relationships of left ventricular (LV) contractile state with LV geometry and hypertrophy in patients with aortic valve disease, and investigated the reversibility of LV hypertrophy and contractility following aortic valve replacement.Preoperative data from quantitative cineangiography and pressure measurements in 132 patients with chronic aortic valve disease, of whom 82 aortic regurgitation (AR), 41 aortic stenosis (AS), and 9 had mixed stenosis and regurgitation (AS-AR), were reviewed. Late after surgery, 59 of the patients (39 with AR, 20 with AS) were studied to elucidate the postoperative reversibility of LV performance and regression of LV hypertrophy.Preoperatively, multiple comparison tests found significant changes in the variables of LV volumes and dimensions in relation to LV contractile state. In stepwise regression analysis, the LV mass index was initially incorporated into a multivariate regression model as an important correlate of LV contractile state. LV geometric variables showed either no or a poor correlation with contractile state. Following aortic valve replacement, improvement of LV contractile dysfunction and regression of LV hypertrophy were limited in many of the patients who had severe preoperative hypertrophy (LV mass index 200% of normal or greater). Further, a close association between LV hypertrophy and LV contractility persisted postoperatively.Our results suggest that the development of LV hypertrophy in terms of an increase in LV mass index, in contrast to changes in geometric patterns, is significantly associated with deterioration in contractile function. LV hypertrophy may become irreversible and pathological at equivalent degrees of hypertrophy (LV mass index >/=200% of normal), regardless of the type of aortic valve lesion.

  View details for DOI 10.1016/j.ejcts.2007.07.003

  View details for Web of Science ID 000250253600007

  View details for PubMedID 17689973

• Successful total arch replacement with long elephant trunk for chronic aortic dissection (DeBakey IIIb) ANNALS OF THORACIC SURGERY Shudo, Y., Taniguchi, K., Matsue, H., Takahashi, T., Toda, K., Hata, H., Sawa, Y. 2007; 84 (2): 659-661

  Abstract

  A 68-year-old man presenting with abdominal distention was found on enhanced computed tomography to have a dilated ascending aorta and aortic dissection (DeBakey IIIb). Through a median sternotomy, we performed a total arch replacement using a four-branched Hemashield graft (Meadox Medical, Oakland, NJ) and a long elephant trunk anastomosis at the base of the innominate artery. Postoperatively, a pseudolumen of the descending aorta was effectively thrombo-excluded to the T12 level. Visceral blood flow was preserved, and the patient's postoperative course was uneventful.

  View details for DOI 10.1016/j.athoracsur.2006.12.013

  View details for Web of Science ID 000248192400053

  View details for PubMedID 17643660

• Hypertrophic cardiomyopathy in China AMERICAN JOURNAL OF CARDIOLOGY Maron, B. J. 2007; 100 (1): 145-146

  View details for DOI 10.1016/j.amjcard.2007.02.069

  View details for Web of Science ID 000247921800028

  View details for PubMedID 17599458

• Radical operation for invasive thymoma with intracaval, intracardiac, and lung invasion JOURNAL OF CARDIAC SURGERY Shudo, Y., Takahashi, T., Ohta, M., Ikeda, N., Matsue, H., Taniguchi, K. 2007; 22 (4): 330-332

  Abstract

  We report a rare case of invasive type AB thymoma (WHO classification system) with intracaval and intracardiac extension into the right atrium. A cardiopulmonary bypass facilitated an en bloc excision of the tumor with a lobectomy, along with a combined resection of the right atrium and reconstruction of the bilateral brachiocephalic veins and right atrium. Aggressive surgical intervention should be considered in such cases, as long-term prognosis is primarily dependent on a complete resection of the extended thymoma.

  View details for DOI 10.1111/j.1540-8191.2007.00417.x

  View details for Web of Science ID 000247943500011

  View details for PubMedID 17661777

• Serotype distribution of Streptococcus mutans a pathogen of dental caries in cardiovascular specimens from Japanese patients JOURNAL OF MEDICAL MICROBIOLOGY Nakano, K., Nemoto, H., Nomura, R., Homma, H., Yoshioka, H., Shudo, Y., Hata, H., Toda, K., Taniguchi, K., Amano, A., Ooshima, T. 2007; 56 (4): 551-556

  Abstract

  The involvement of oral bacteria in the pathogenesis of cardiovascular disease has been studied, with Streptococcus mutans, a pathogen of dental caries, detected in cardiovascular lesions at a high frequency. However, no information is available regarding the properties of S. mutans detected in those lesions. Heart valve specimens were collected from 52 patients and atheromatous plaque specimens from 50 patients, all of whom underwent cardiovascular operations, and dental plaque specimens were taken from 41 of those subjects prior to surgery. Furthermore, saliva samples were taken from 73 sets of healthy mothers (n=73) and their healthy children (n=78). Bacterial DNA was extracted from all specimens, then analysed by PCR with S. mutans-specific and serotype-specific primer sets. The detection rates of S. mutans in the heart valve and atheromatous plaque specimens were 63 and 64 %, respectively. Non-c serotypes were identified with a significantly higher frequency in both cardiovascular and dental plaque samples from the subjects who underwent surgery as compared to serotype c, which was detected in 70-75 % of the samples from the healthy subjects. The serotype distribution in cardiovascular patients was significantly different from that in healthy subjects, suggesting that S. mutans serotype may be related to cardiovascular disease.

  View details for DOI 10.1099/jmm.0.47051-0

  View details for Web of Science ID 000245795600018

  View details for PubMedID 17374899

• Simple and easy method for chordal reconstruction during mitral valve repair ANNALS OF THORACIC SURGERY Shudo, Y., Taniguchi, K., Takahashi, T., Matsue, H. 2006; 82 (1): 348-349

  Abstract

  We describe a simple reproducible method for chordal replacement using expanded polytetrafluoroethylene sutures during a mitral valve repair. With this technique, fine length adjustments of the new chordae are easy to make and it is possible to tie the two ends of the suture securely without slippage.

  View details for DOI 10.1016/j.athorscur.2005.05.087

  View details for Web of Science ID 000238521600071

  View details for PubMedID 16798256