Bio


I am a board-certified attending cardiothoracic surgeon in Japan. Throughout my clinical experience and research, I found that insufficient myocardial blood flow had little impact on myocardial functional recovery since percutaneous coronary intervention or coronary artery bypass grafting (CABG) could approach and supply blood flow to the superficial large coronary arteries, but not to intramyocardial microvascular arteries, particularly where microvasculature was either scarce or absent. In addition, myocardial ischemia-reperfusion (I/R) adversely affected cardiac functional recovery in ischemic hearts, including transplanted hearts. Therefore, I have a keen interest in addressing myocardial microvascular dysfunction and myocardial I/R injury in research.
During my Ph.D. in cardiovascular surgery, I focused on a prostacyclin analog that has thromboxane A2 synthase inhibitory activity and can promote angiogenesis and restore myocardial blood flow through proangiogenic and vasodilatory effects. I applied a microform of this compound in the porcine ischemia cardiomyopathy model with a direct epicardial placement, elucidating promoted myocardial angiogenesis, leading to myocardial function recovery. Then, I developed nanoparticles (NPs) that incorporated this compound which I subsequently applied to a rat ischemia myocardial reperfusion model with intravenous injection to elucidate attenuated myocardial I/R injury with selective accumulation in the ischemic myocardium, better-preserved capillary networks, a better-preserved myocardial blood flow, and a smaller infarct size. Furthermore, I have worked on tissue engineering for myocardial regeneration using induced pluripotent stem cells (iPSCs) and adipose-derived mesenchymal stem cells. With human iPSCs-derived cardiomyocyte sheets of direct implantation on the ischemic myocardial tissue, we elucidated myocardial regeneration through thickened myocardial tissue, proangiogenic effects, improved cardiac performance, and attenuated left ventricular remodeling in both small and large animals. These works have already been published (below are representative), and I gained several academic awards and research grants (ongoing research support; Japan Heart Foundation/Bayer Research Grant Abroad, 01/01/2022 - 12/31/2022).
My career goal is to become a leader in academic cardiovascular surgery. During my postdoctoral fellowship, I plan to develop novel therapeutic methods to obtain better outcomes for ischemic heart disease in which there is room for improvement through engineering analysis and the creation of innovative solutions. I am extremely excited to start on the proposed project, as it perfectly intertwines my bioengineering background and clinical interests. As such, the School of Medicine Dean's Postdoctoral Fellowship will be invaluable to my development as a young investigator. Dr. Woo is an exceptional mentor with remarkable renown for training academic surgeons and Stanford University provides incredible resources for research. I feel extremely fortunate to have such an ideal environment to carry out this project and continue advancing the field of cardiothoracic surgery through bioengineering.

Honors & Awards


  • Best Scientific Paper, The Japanese Association for Thoracic Surgery (2019)
  • Best Teaching Award, National Cerebral, and Cardiovascular Center, Japan (2019)
  • Japan Heart Foundation/Bayer Research Grant Abroad, Bayer foundation (2019)
  • Young Investigator’s Award, Department of Surgery, Osaka University Graduate School of Medicine, Japan (2019)
  • Best of Basic Scientific Research for Cardiovascular Surgery, Japan Circulation Society (2018)
  • Young Investigator’s Award, Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Japan (2018)
  • Young Investigator Award, The 60th Annual Meeting of Kansai Thoracic Surgical Association, Japan (2017)
  • Basic Research Award (Hearse-Yamamoto Award), Japanese Society for Cardiovascular Surgery (2016)
  • Best of Basic Scientific Poster Award, American Heart Association (2016)
  • Young Investigator Award, The 59th Annual Meeting of Kansai Thoracic Surgical Association, Japan (2016)
  • Young Investigator Award, Japanese Surgical Society (2016)

Boards, Advisory Committees, Professional Organizations


  • Board Certified Instructor of Cardiovascular Surgery, The Japanese Society of Cardiovascular Surgery, ID: 21-1436 (2021 - Present)
  • Board Certified International Cardiovascular Surgeon, The Asian Society for Cardiovascular Surgery, ID: 842-6777 (2019 - Present)
  • Board Certified Cardiovascular Surgeon, The Japanese Society of Cardiovascular Surgery ID: 5001419 (2017 - Present)
  • Board Certified General Surgeon, The Japan Surgical Society ID: 1003775 (2013 - Present)

Professional Education


  • PhD, Osaka University Graduate School of Medicine, Faculty of Medicine, Department of Cardiovascular Surgery, Osaka, Japan (2018)
  • MD, Shimane University, Shimane, Japan (2007)

Stanford Advisors


All Publications


  • Prostacyclin Analogue-Loaded Nanoparticles Attenuate Myocardial Ischemia/Reperfusion Injury in Rats. JACC. Basic to translational science Yajima, S., Miyagawa, S., Fukushima, S., Sakai, Y., Iseoka, H., Harada, A., Isohashi, K., Horitsugi, G., Mori, Y., Shiozaki, M., Ohkawara, H., Sakaniwa, R., Hatazawa, J., Yoshioka, Y., Sawa, Y. 2019; 4 (3): 318-331

    Abstract

    Intravenously injected ONO-1301-containing nanoparticles (ONO-1301NPs), unlike an ONO-1301 solution, selectively accumulated in the ischemia/reperfusion (I/R)-injured myocardium of rats and contributed to the prolonged retention of ONO-1301 in the targeted myocardial tissue. In the ischemic area, proangiogenic cytokines were up-regulated and inflammatory cytokines were down-regulated upon ONO-1301NP administration. Consequently, ONO-1301NP-injected rats exhibited a smaller infarct size, better-preserved capillary networks, and a better-preserved myocardial blood flow at 24 h after I/R injury, compared with those in vehicle-injected or ONO-1301 solution-injected rats. ONO-1301NPs attenuate the myocardial I/R injury via proangiogenic and anti-inflammatory effects of the drug.

    View details for DOI 10.1016/j.jacbts.2018.12.006

    View details for PubMedID 31312756

    View details for PubMedCentralID PMC6609885

  • Microvascular Dysfunction Related to Progressive Left Ventricular Remodeling due to Chronic Occlusion of the Left Anterior Descending Artery in an Adult Porcine Heart. International heart journal Yajima, S., Miyagawa, S., Fukushima, S., Isohashi, K., Watabe, T., Ikeda, H., Horitsugi, G., Harada, A., Sakaniwa, R., Hatazawa, J., Sawa, Y. 2019; 60 (3): 715-727

    Abstract

    Occlusion of a major coronary artery induces myocardial infarction (MI), leading to left ventricle (LV) remodeling due to progressive microvasculature dysfunction. Irreversible impairment in microvascular function has been suggested to extend from the infarcted region into the infarct-border or remote regions, depending on the time to revascularization. Our aim was to determine whether the occlusion of a major coronary artery induces microvascular dysfunction in the adjacent area perfused by intact coronary arteries using a porcine model for chronic total occlusion of the left anterior descending artery (LAD). MI was induced via an ameroid constrictor ring around the LAD in adult Göttingen pigs (Sus scrofa domesticus, n = 5). Age-matched normal pigs were treated as controls (n = 3). Cardiac magnetic resonance showed reduced systolic regional wall motion in the left circumflex (LCx) and right coronary artery (RCA) territories, with a progressively worsening motion in the infarction-adjacent area over an eight-week period. On 13N-ammonia positron emission tomography (PET), myocardial blood flow (MBF) during hyperemia was significantly greater in the LCx and RCA territories (particularly in the infarction-adjacent area) compared to that in the LAD territory at four weeks after infarct induction. Subsequently, the flow significantly decreased, approaching that in the LAD territory at eight weeks after infarct induction. Fluoroscopy-guided pressure-wire studies showed significantly higher microvascular resistance in the LCx area at eight weeks compared to that in controls. Electron microscopy showed endothelium swelling and microvasculature disruption in areas adjacent to the LCx and RCA territories. Anterior MI caused coronary microvascular dysfunction in the adjacent area, associated with a reduced MBF and regional wall motion.

    View details for DOI 10.1536/ihj.18-346

    View details for PubMedID 31105143

  • A prostacyclin agonist and an omental flap increased myocardial blood flow in a porcine chronic ischemia model. The Journal of thoracic and cardiovascular surgery Yajima, S., Miyagawa, S., Fukushima, S., Sakai, Y., Isohashi, K., Watabe, T., Ikeda, H., Horitsugi, G., Harada, A., Sakaniwa, R., Hatazawa, J., Sawa, Y. 2018; 156 (1): 229-241.e14

    Abstract

    We hypothesized that therapeutic efficacy may be augmented by a combination of placing a sheet immersed in ONO-1301SR, a slow-release synthetic prostacyclin agonist-inducing multiproangiogenic cytokines, over the left ventricle and a pedicled omental flap in a chronic myocardial infarct heart.A minipig chronic myocardial infarction was generated by placing an ameroid constrictor ring around the left anterior descending artery for 4 weeks. The minipigs were then assigned into 4 groups of 6 each: sham, omental flap only, ONO-1301SR only, and ONO-1301SR combined with an omental flap (combined). Four weeks after treatment, therapeutic efficacy was evaluated histologically and via several modalities used in the clinical setting.In an angiogram and pressure wire study, the combined group induced development of collateral arteries to decrease the resistance and increase the flow reserve of microvasculature in the left circumflex territory. In a 13N-ammonia positron emission tomography study, the combined group displayed a prominent increase in myocardial blood flow and myocardial flow reserve in the left circumflex territory, particularly at the infarct-border region. Consequently, the combined group showed greater regional cardiac function in the left circumflex territory particularly at the infarct-border region, contributing to a greater global ejection fraction with a smaller left ventricular endosystolic volume. Pathologically, attenuated fibrosis, nonswollen myocytes, and upgraded capillary density and proangiogenic cytokines were prominent in the combined group.ONO-1301SR combined with a pedicled omental flap synergistically promoted myocardial angiogenesis, leading to function recovery in a porcine chronic myocardial infarction model.

    View details for DOI 10.1016/j.jtcvs.2018.02.086

    View details for PubMedID 29627179

  • Early Outcomes of Intuity Rapid Deployment Aortic Valve Replacement Compared With Conventional Biological Valves in Japanese Patients. Circulation journal : official journal of the Japanese Circulation Society Ono, Y., Yajima, S., Kainuma, S., Kawamoto, N., Tadokoro, N., Kakuta, T., Koga-Ikuta, A., Fujita, T., Fukushima, S. 2022

    Abstract

    This study aimed to elucidate the short-term surgical outcomes and hemodynamics of the Intuity valve compared to the standard bioprosthesis in Japanese patients.Methods and Results: Among the 307 consecutive patients who underwent aortic valve replacement (AVR) between February 2019 and March 2021, the Intuity valve was implanted in 95 patients (Intuity group) and a conventional stented bioprosthesis was implanted in 193 patients (conventional group). After propensity score matching, there was no significant difference in in-hospital mortality between the Intuity (n=2, 3%) and conventional groups (n=0, P=0.490). Operation, cardiopulmonary bypass, and aortic cross-clamping times were significantly shorter in the Intuity group. Although the effective orifice area index, trans-prosthetic mean pressure gradient, and peak velocity were similar between the 2 groups at 1 week postoperatively, the Intuity group showed a better mean pressure gradient and peak velocity at 1 year postoperatively. Complete atrioventricular block requiring permanent pacemaker implantation developed in 2 patients (3%) in the Intuity group and none in the conventional group (P=0.476). Mild or greater paravalvular leakage was present in 8 patients (13%) in the Intuity group and 2 patients (3%) in the conventional group (P=0.095).AVR using the Intuity valve in Japanese patients is satisfactory, with a better valve performance and a low incidence of complete atrioventricular block at 1 year postoperatively.

    View details for DOI 10.1253/circj.CJ-21-0959

    View details for PubMedID 35569971

  • Late spontaneous internal thoracic artery graft dissection after coronary bypass grafting: a case report EUROPEAN HEART JOURNAL-CASE REPORTS Ishibuchi, K., Yajima, S., Yamamoto, W., Otsuji, S. 2022; 6 (2): ytac040

    Abstract

    Internal thoracic artery (ITA) grafts are commonly used for coronary artery bypass grafting, with dissection to the graft being a rare occurrence. Herein, we describe a case of spontaneous ITA graft dissection occurring 11 years after grafting, with no clear precipitating incidence.The patient was a 61-year-old man who presented with a 3-month history of chest pain and dyspnoea. Dissection of the left internal thoracic artery (LITA) graft was observed on angiography, with a thrombolysis in the myocardial infarction (TIMI) grade 2 blood flow. Intravascular ultrasound confirmed an intimal tear in the proximal graft, with an intramural haematoma. In the absence of atherosclerotic changes, the dissection was treated directly using multiple drug-eluting stents to prevent further extension of the intramural haematoma proximally into the subclavian artery and distally to the anastomosis site. Post-procedural angiography revealed an enlarged true lumen of the LITA, shrinking of the intramural haematoma, and improvement in blood flow to a TIMI grade 3. Chest symptoms resolved immediately after the procedure, with the patient remaining asymptomatic over the 6-month period following the procedure.Dissection of the ITA graft can occur spontaneously long after the initial grafting. Intravascular ultrasound is useful for diagnosis. Ensuring adequate coverage of the edges of the dissection with stenting could prevent further extension of the intramural haematoma.

    View details for DOI 10.1093/ehjcr/ytac040

    View details for Web of Science ID 000764048700029

    View details for PubMedID 35295725

    View details for PubMedCentralID PMC8922694

  • Perceval sutureless aortic valve replacement after ascending aortic replacement. Clinical case reports Yajima, S., Satoh, A., Sekiya, N., Yamazaki, S., Uemura, H., Tanaka, H., Yamamura, M., Sakaguchi, T. 2021; 9 (12): e05126

    Abstract

    In patients with a narrow sinotubular junction, small sinus of Valsalva, or extensibility loss in the aortic root, aortic valve replacement (AVR) with a standard valve is challenging due to limited surgical field. Detailed preoperative measurements of the aortic root render performing AVR using the Perceval valve easy.

    View details for DOI 10.1002/ccr3.5126

    View details for PubMedID 34917364

    View details for PubMedCentralID PMC8645176

  • Repair of pacemaker lead-induced right ventricular perforation via a left mini-thoracotomy. Journal of cardiology cases Uemura, H., Yajima, S., Sekiya, N., Yamazaki, S., Satoh, A., Tanaka, H., Yamamura, M., Sakaguchi, T. 2021; 24 (6): 307-309

    Abstract

    Cardiac perforation is a rare but serious and life-threatening complication of permanent pacemaker implantation, with an incidence of 0.1-6%. Surgery is usually performed through a median sternotomy; however, sternotomy-related morbidity remains a concern. Herein, we report a case of surgical repair performed via a left mini-thoracotomy for a right ventricular perforation caused by implantation of a permanent pacemaker lead in a 56-year-old woman. Through the left fifth intercostal space, the pacemaker lead was observed to have penetrated the left ventricular myocardium, reaching the pericardium. The lead had passed through the right ventricle and the inferior ventricular septum and protruded from the left ventricular myocardium. After pacemaker lead removal, a dark blow-out type hemorrhage occurred; hence, repair was performed using a pair of pledgeted Mattress sutures. In conclusion, left mini-thoracotomy provides an adequate surgical field and has less impact on hemodynamics when operating at the cardiac apex. .

    View details for DOI 10.1016/j.jccase.2021.05.008

    View details for PubMedID 34917217

    View details for PubMedCentralID PMC8642623

  • Surgical Strategy for Chronic Type B Dissecting Aortic Aneurysm to Prevent Aorta-Related Events. Annals of vascular surgery Ryomoto, M., Sakaguchi, T., Tanaka, H., Yamamura, M., Sekiya, N., Yajima, S., Uemura, H., Sato, A. 2021

    Abstract

    This study was aimed to evaluate the outcomes of performing open repair or thoracic endovascular aortic repair for chronic type B dissecting aortic aneurysm.From July 2004 to February 2019, 52 patients underwent surgery as open repair (n = 32) or endovascular repair (n = 20) for chronic type B dissecting aortic aneurysm. Replacement of the aorta was limited to the aneurysmal portion with or without reconstructing the visceral arteries or the segmental arteries. Stent grafts were deployed in the true lumen above the celiac artery to cover the primary entry for even DeBakey IIIb dissection.Operative mortality and morbidity rates, including spinal cord ischemia incidence, did not differ between the groups. Operative mortality and morbidity rates, including spinal cord ischemia incidence, did not differ between the groups. In the endovascular repair group, 3 patients died due to rupture of residual false lumen in the early, and late postoperative follow-up. The 5-year rate of freedom from all-cause death, aorta-related death, and aorta-related event were 84% ± 6%, 94% ± 3% and 84% ± 6%. The endovascular repair was independently associated with all-cause death (hazard ratio [HR], 5.7; confidence interval [CI], 1.02-31.6; P = 0.04) and aorta-related event (HR, 30.9; CI 4.9-195.0; P < 0.001). In the open group, postoperative residual aortic diameter was an independent predictor of aorta-related events, and the threshold was 41 mm.Open repair remains a better option than simple endovascular repair alone in DeBakey IIIb dissection, but the distal un-resected aortic portion over 41 mm was associated with late aortic events.

    View details for DOI 10.1016/j.avsg.2021.10.046

    View details for PubMedID 34788707

  • Inactive large cerebral hemorrhage is not exacerbated by the adjustment of anticoagulation post open-heart surgery. Journal of cardiology cases Satoh, A., Yajima, S., Sekiya, N., Yamazaki, S., Uemura, H., Ueda, D., Tanaka, H., Yamamura, M., Sakaguchi, T. 2021; 24 (4): 186-189

    Abstract

    Optimal timing of open-heart surgery for the treatment of patients with cerebral hemorrhage remains controversial because systemic heparinization may lead to catastrophic bleeding. Several recent reports have shown that patients who undergo open-heart surgery .within a few weeks of cerebral hemorrhage have a much lower risk of exacerbated bleeding than previously considered. Herein, we report a case of left atrial myxoma and large hemorrhagic embolic stroke, which was successfully operated on with no exacerbation of cerebral hemorrhage. Careful assessment of time-course changes in cerebral hemorrhage by neurological imaging and adjustment of anticoagulation can help prevent the exacerbation of postoperative cerebral hemorrhage and neurological deterioration. .

    View details for DOI 10.1016/j.jccase.2021.04.003

    View details for PubMedID 35059053

    View details for PubMedCentralID PMC8758593

  • Off-Pump Resection of an Epicardial Cyst by Using a Minimally Invasive Approach. The Annals of thoracic surgery Uemura, H., Yajima, S., Ryomoto, M., Sekiya, N., Yamashita, K., Tanaka, H., Yamamura, M., Satoh, A., Ueda, D., Sakaguchi, T. 2021; 112 (2): e119-e121

    Abstract

    A 25-year-old man presented with palpitations and subsequently received a diagnosis of a large epicardial cyst (6.8 × 3.8 cm) originating from the left ventricle. The cyst compressed the left atrium and ventricle and led to left ventricular diastolic dysfunction. Contrast-enhanced chest computed tomography revealed that the circumflex artery passed over or through the cyst. We successfully resected the cyst without using cardiopulmonary bypass through a left mini-thoracotomy with thoracoscopic assistance. The diastolic dysfunction improved after the procedure. Most epicardial cysts may be treated in this fashion if the cyst is located in the left side of the heart.

    View details for DOI 10.1016/j.athoracsur.2020.11.050

    View details for PubMedID 33444579

  • Reverse remodelling after aortic valve replacement for chronic aortic regurgitation. Interactive cardiovascular and thoracic surgery Koga-Ikuta, A., Fukushima, S., Kawamoto, N., Saito, T., Shimahara, Y., Yajima, S., Tadokoro, N., Kakuta, T., Fukui, T., Fujita, T. 2021; 33 (1): 10-18

    Abstract

    This study aimed to assess the long-term outcomes and investigate the factors related to left ventricular (LV) reverse remodelling after aortic valve replacement (AVR) in patients with chronic aortic regurgitation (AR).A total of 246 patients who underwent AVR for chronic AR at our institution were included in this retrospective study. Primary end-points included all-cause mortality, cardiac mortality and major adverse cerebral and cardiovascular events. Secondary end-points included cardiac function on echocardiography 1 year after surgery. We explored the predictive factors for reverse remodelling 1 year after surgery.The 10-year survival rate was 86.0%, with no cardiac deaths in 93.8% and no major adverse cerebral and cardiovascular events in 79.9% of patients. Postoperative LV function and symptoms were significantly improved 1 year after surgery, but 34 patients (13.8%) did not recover normal function and structure. A significant negative correlation was found between the incidence of cardiac death and major adverse cerebral and cardiovascular events and reverse remodelling. Multivariate logistic regression identified preoperative LV ejection fraction (P = 0.001, odds ratio = 1.057) and LV end-systolic dimension index (P = 0.038, odds ratio = 0.912) as significant predictive factors of reverse remodelling 1 year after surgery.Preoperative LV ejection fraction and LV end-systolic dimension index were predictive factors for reverse remodelling after surgery, which was associated with late outcomes. Earlier surgery may thus help to restore normal LV function and achieve better late outcomes after AVR for AR.

    View details for DOI 10.1093/icvts/ivab046

    View details for PubMedID 33615334

    View details for PubMedCentralID PMC8691506

  • Graft Traction Resolved Left Ventricular Outflow Tract Obstruction. The Annals of thoracic surgery Sekiya, N., Ryomoto, M., Tanaka, H., Yamamura, M., Yamashita, K., Yajima, S., Uemura, H., Satoh, A., Ueda, D., Sakaguchi, T. 2021; 111 (6): e415-e417

    Abstract

    We admitted a 76-year-old woman for treatment of an ascending aortic aneurysm with left ventricular outflow tract (LVOT) obstruction and systolic anterior motion (SAM) of the mitral valve. Echocardiography showed an elevated velocity of the LVOT flow with a sigmoid septum. Mild mitral regurgitation was also detected due to SAM. We performed a graft replacement of the ascending aorta, after which the LVOT obstruction and SAM were resolved. We report a case in which the traction of a graft likely released the compression on the aortic root and ventricular septum.

    View details for DOI 10.1016/j.athoracsur.2020.09.073

    View details for PubMedID 33352177

  • Emergency sandwich patch repair via right ventricular incision for postinfarction ventricular septal defects: a case series. European heart journal. Case reports Shimahara, Y., Fukushima, S., Yajima, S., Tadokoro, N., Kakuta, T., Asaumi, Y., Kobayashi, J., Fujita, T. 2021; 5 (5): ytab141

    Abstract

    The surgical treatment for postinfarction ventricular septal defect (VSD) remains challenging, especially in emergency cases. Several authors have reported the efficacy of a sandwich patch VSD repair via a right ventricular (RV) incision. However, this procedure remains uncommon, and its efficacy is still unknown, especially when performed under an emergency.We were able to perform sandwich patch VSD repair via an RV incision on seven consecutive patients with VSD following an ST-segment elevation myocardial infarction (STEMI) from March 2017 to December 2019. Bovine pericardial patches were used for sandwich patches. Two patients developed inferior STEMI, and the other patients developed anterior STEMI. Six patients received intra-aortic balloon pump prior to surgery, and the other received extracorporeal membrane oxygenation with Impella. The interval between the diagnosis of VSD and surgery was within 1 day in all patients except one (5 days). All seven patients underwent VSD repair in the emergency status. Four patients underwent concomitant coronary artery bypass grafting. The hospital mortality rate was 14.3% (1/7). Early postoperative transthoracic echocardiography revealed that only one patient developed more than trace residual shunt. The postoperative right atrial pressure was not significantly elevated at ≤12 mmHg in all patients. No patient developed early postoperative prolonged low cardiac output syndrome.In patients with postinfarction VSD, a sandwich patch VSD repair via an RV incision is a promising procedure with a low incidence of residual shunt development and hospital mortality, even in emergency cases.

    View details for DOI 10.1093/ehjcr/ytab141

    View details for PubMedID 34268476

    View details for PubMedCentralID PMC8276610

  • Benefits of robotically-assisted surgery for complex mitral valve repair. Interactive cardiovascular and thoracic surgery Fujita, T., Kakuta, T., Kawamoto, N., Shimahara, Y., Yajima, S., Tadokoro, N., Kitamura, S., Kobayashi, J., Fukushima, S. 2021; 32 (3): 417-425

    Abstract

    To determine whether robotic mitral valve repair can be applied to more complex lesions compared with minimally invasive direct mitral valve repair through a right thoracotomy.We enrolled 335 patients over a 9-year period; 95% of the robotic surgeries were performed after experience performing direct mitral valve repair.The mean age in the robotic versus thoracotomy repair groups was 61 ± 14 vs 55 ± 11 years, respectively (P < 0.001); 97% vs 100% of the patients, respectively, had degenerative aetiologies. Repair complexity was simple in 106 (63%) vs 140 (84%), complex in 34 (20%) vs 20 (12%) and most complex in 29 (17%) vs 6 (4%) patients undergoing robotic versus thoracotomy repair, respectively. The average complexity score with robotic repair was significantly higher versus thoracotomy repair (P < 0.001). The robotic group underwent more chordal replacement using polytetrafluoroethylene and less resections. All patients underwent ring annuloplasty. Cross-clamp time did not differ between the groups, and no strokes or deaths occurred. More patients undergoing robotic repair underwent concomitant procedures versus the thoracotomy group (30% vs 14%, respectively; P < 0.001). The overall repair rate was 100%, with no early mortality or strokes in either group. Postoperative mean residual mitral regurgitation was 0.3 in both groups, and the mean pressure gradient through the mitral valve was 2.4 vs 2.7 mmHg (robotic versus thoracotomy repair, respectively; P = 0.031).Robotic surgery can be applied to repair more complex mitral lesions, with excellent early outcomes.

    View details for DOI 10.1093/icvts/ivaa271

    View details for PubMedID 33221856

    View details for PubMedCentralID PMC8906674

  • Successful surgical resection and reconstruction for a huge primary cardiac lymphoma filling the right heart. Journal of cardiac surgery Taguchi, T., Fukushima, S., Yajima, S., Saito, T., Kawamoto, N., Tadokoro, N., Kakuta, T., Fujita, T. 2021; 36 (1): 342-344

    Abstract

    Primary cardiac lymphoma (PCL) is rare, with a frequency of 1.0%-1.6% among cardiac malignant tumors. Chemotherapy is often selected as a first-line treatment for PCL. However, when the tumor causes heart failure or life-threatening hemodynamic collapse, antecedent urgent surgery is required. We herein report a successful case of complete tumor resection and reconstruction of the right atrium and right ventricle using a bovine pericardial patch combined with tricuspid valve replacement in a patient with a huge PCL filling the right heart that manifested as tricuspid valve stenosis and subsequent heart failure.

    View details for DOI 10.1111/jocs.15152

    View details for PubMedID 33124696

  • Durable ventricular assist device implantation for systemic right ventricle: a case series. European heart journal. Case reports Tadokoro, N., Fukushima, S., Hoashi, T., Yajima, S., Taguchi, T., Shimizu, H., Fujita, T. 2020; 4 (6): 1-9

    Abstract

    A systemic right ventricle (RV) after atrial switch in transposition of the great arteries (TGA) or congenitally corrected TGA (ccTGA) often results in advanced heart failure in adulthood.Four patients with INTERMACS Class III underwent durable ventricular assist device (VAD) implantation for a systemic RV. Two patients were diagnosed with ccTGA and underwent tricuspid valve replacement, and two were diagnosed with TGA in childhood and underwent Mustard repair. The two patients with ccTGA received an EVAHEART (Sun Medical, Nagano, Japan) and HeartMate 3 (Abbott Laboratories, Abbott Park, IL, USA) at the age of 56 years and 34 years, respectively. Of the patients with TGA, one received a Heartmate II at age 40 years, and one received a HeartMate 3 at age 40 years. All patients were weaned from cardiopulmonary bypass without subpulmonic VAD support and transferred to the intensive care unit with optimum VAD support. No in-hospital deaths, cerebrovascular accidents, or other major complications occurred. The post-VAD right heart catheter study showed a remarkable reduction in pulmonary capillary wedge pressure in all patients.The indications for and surgical technique of durable VAD implantation for a systemic RV after atrial switch of TGA or ccTGA have not been fully established. A durable VAD, including the HeartMate 3, was successfully implanted in four such patients in this study. Pre-operative three-dimensional computed tomography images and intraoperative transoesophageal echocardiography guidance helped to determine the positions of the inflow and pump.

    View details for DOI 10.1093/ehjcr/ytaa359

    View details for PubMedID 33629019

    View details for PubMedCentralID PMC7891278

  • Influence of Induction Therapy Using Basiliximab With Delayed Tacrolimus Administration in Heart Transplant Recipients - Comparison With Standard Tacrolimus-Based Triple Immunosuppression. Circulation journal : official journal of the Japanese Circulation Society Watanabe, T., Yanase, M., Seguchi, O., Fujita, T., Hamasaki, T., Nakajima, S., Kuroda, K., Kumai, Y., Toda, K., Iwasaki, K., Kimura, Y., Mochizuki, H., Anegawa, E., Sujino, Y., Yagi, N., Yoshitake, K., Wada, K., Matsuda, S., Takenaka, H., Ikura, M., Nakagita, K., Yajima, S., Matsumoto, Y., Tadokoro, N., Kakuta, T., Fukushima, S., Ishibashi-Ueda, H., Kobayashi, J., Fukushima, N. 2020; 84 (12): 2212-2223

    Abstract

    Appropriate indications and protocols for induction therapy using basiliximab have not been fully established in heart transplant (HTx) recipients. This study elucidated the influence of induction therapy using basiliximab along with delayed tacrolimus (Tac) initiation on the outcomes of high-risk HTx recipients.Methods and Results:A total of 86 HTx recipients treated with Tac-based immunosuppression were retrospectively reviewed. Induction therapy was administered to 46 recipients (53.5%) with impaired renal function, pre-transplant sensitization, and recipient- and donor-related risk factors (Induction group). Tac administration was delayed in the Induction group. Induction group subjects showed a lower cumulative incidence of acute cellular rejection grade ≥1R after propensity score adjustment, but this was not significantly different (hazard ratio [HR]: 0.63, 95% confidence interval [CI]: 0.37-1.08, P=0.093). Renal dysfunction in the Induction group significantly improved 6 months post-transplantation (P=0.029). The cumulative incidence of bacterial or fungal infections was significantly higher in the Induction group (HR: 10.6, 95% CI: 1.28-88.2, P=0.029).These results suggest that basiliximab-based induction therapy with delayed Tac initiation may suppress mild acute cellular rejection and improve renal function in recipients with renal dysfunction, resulting in its non-inferior outcome, even in high-risk patients, when applied to the appropriate recipients. However, it should be carefully considered in recipients at a high risk of bacterial and fungal infections.

    View details for DOI 10.1253/circj.CJ-20-0164

    View details for PubMedID 33148937

  • Early results of robotically assisted mitral valve repair in a single institution: report of the first 100 cases. General thoracic and cardiovascular surgery Kakuta, T., Fukushima, S., Shimahara, Y., Yajima, S., Tadokoro, N., Minami, K., Kobayashi, J., Fujita, T. 2020; 68 (10): 1079-1085

    Abstract

    Robotically assisted mitral valve repair was approved for use in Japan in April 2018. The study objective was to assess the safety and clinical outcomes of robotic mitral valve surgery in the first 100 cases performed in our center.We reviewed the first 100 patients who underwent robotic primary mitral valve repair, including concomitant procedures, from April 2018 to August 2019. The cause of mitral valve disease was degenerative (n = 94), endocarditis (n = 2), functional (n = 2), and other (n = 2).There was no in-hospital or 30-day mortality. Mitral valve repair was completed in all patients. Only one patient required conversion to full sternotomy due to left ventricular apex bleeding. In echocardiography performed before hospital discharge, the mitral regurgitation was graded as none or trivial in 94 patients (94%) and mild in 4 (4%). Only two patients required surgical re-intervention due to postoperative hemolysis with moderate mitral regurgitation. For patients who underwent the mitral valve procedure alone, the median times of the total operation, cardiopulmonary bypass, aortic clamping, and console usage were 185, 112, 71, and 60 min, respectively. The learning curve showed that the operation time decreased slightly during the first ten cases and then plateaued at a mean of approximately 180 min.Robotically assisted mitral valve repair was feasible, safe, and therapeutically effective in the first 100 cases, with a minimal learning curve. The robotically assisted approach provides a high-quality surgical view and tremorless suture/cut handling, which will contribute to further development of minimally invasive mitral valve surgery.

    View details for DOI 10.1007/s11748-020-01317-2

    View details for PubMedID 32072433

  • Long-term outcomes after reoperation for mitral paravalvular leaks: a single-centre experience. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Yajima, S., Fukushima, S., Yamashita, K., Shimahara, Y., Tadokoro, N., Kakuta, T., Sakaniwa, R., Kobayashi, J., Fujita, T. 2020

    Abstract

    We aimed to analyse the pathology of paravalvular leak (PVL), and determine the long-term outcomes of redo mitral valve replacement and risk factors of all-cause mortality.Seventy-nine patients (mean age 70 ± 9 years; 54 female, 68%) who underwent redo mitral valve replacement for mitral PVL between January 2000 and May 2019 were retrospectively reviewed. Indications for PVL intervention were haemolytic anaemia (57/79, 72%), New York Heart Association class III/IV congestive heart failure (56/79, 71%) and prosthetic valve endocarditis with PVL (2/79, 3%).PVL most commonly occurred at lateral sectors (42/79, 55%). Early mortality occurred in 2 patients (3%) due to low cardiac output syndrome. Two patients (3%) had residual PVL at discharge. Sixteen patients (23%) developed late PVL (mean follow-up, 3.4 ± 2.9 years), among whom 11 (69%) developed PVL at same area as that preoperatively. Additionally, 9 patients (56%) developed PVL at lateral sectors in late follow-up. At 1, 5 and 10 years, the survival rate was 93%, 72% and 45%; rate of freedom from cardiac death was 96%, 92% and 78%; and rate of freedom from PVL recurrence was 94%, 82% and 54%, respectively. Chronic kidney disease was the only risk factor in the multivariate analysis for mortality [P = 0.013; hazard ratio 4.0 (1.4-11.0)].Surgery for mitral PVL confers reasonable early and long-term outcomes. Greater attention to the anterolateral annulus may help prevent PVL.

    View details for DOI 10.1093/ejcts/ezaa331

    View details for PubMedID 32944776

  • Central conversion from peripheral extracorporeal life support for patients with refractory congestive heart failure. Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs Fukushima, S., Tadokoro, N., Koga, A., Shimahara, Y., Yajima, S., Kakuta, T., Kuroda, K., Nakajima, S., Watanabe, T., Yanase, M., Fukushima, N., Kobayashi, J., Fujita, T. 2020; 23 (3): 214-224

    Abstract

    Conversion from peripheral extracorporeal life support (ECLS) to the central one can improve and stabilize hemodynamics in patients with refractory congestive heart failure-related multiorgan failure, whereas indication and selection of the type of the central ECLS have not been fully established. Institutional outcome of the conversion therapy was herein reviewed to verify indication and selection of three types of central ECLS. This study enrolled an institutional consecutive surgical series of 24 patients with refractory congestive heart failure under peripheral ECLS, related to fulminant myocarditis (n = 15), dilated cardiomyopathy (n = 5), or acute myocardial infarction (n = 4). They were converted to central Y-extracorporeal membrane oxygenation (ECMO, n = 6), extracorporeal ventricular assist device (EC-VAD, n = 12), or pump catheter (n = 6), dependent upon the degree of multiorgan failure. Despite the different degree of multiorgan failure prior to the conversion, improvement in end-organ perfusion and reduction in right atrial and pulmonary artery pressure were promptly achieved regardless of the type of the central ECLS. There were five in-hospital mortalities (21%) during the central ECLS, whereas mechanical support was weaned-off in 11 cases (46%) and durable LVAD was subsequently implanted for bridge to transplantation in eight cases (33%). Conversion from the peripheral ECLS to the central ones, such as central Y-ECMO, EC-VAD or pump catheter, promptly established a sufficient support with heart and lung unloading in patients with refractory congestive heart failure.

    View details for DOI 10.1007/s10047-020-01157-0

    View details for PubMedID 32076901

  • Robotic mitral valve repair for rheumatic mitral stenosis and regurgitation: a case report. European heart journal. Case reports Yajima, S., Fukushima, S., Kakuta, T., Fujita, T. 2020; 4 (1): 1-6

    Abstract

    Rheumatic mitral valve (MV) disease is the major cause of congestive cardiac failure in children and young adults, particularly in developing countries. Mitral valve repair with minimum prosthetic material is the gold standard treatment for this condition. However, MV repair for rheumatic MV disease is known to be technically demanding.A 27-year-old woman without a history of cardiac disease presented with dyspnoea on exertion. Echocardiography revealed rheumatic severe mitral stenosis and regurgitation, with thickening of the bileaflets, doming of the anterior leaflet, shortening of the posterior leaflet, fusions of the lateral and particularly the medial commissure, and enlargement of the mitral annulus. We successfully performed robot-assisted MV repair with bicommissural release, patch augmentation of the two leaflets, and implantation of an originally sized partial band.Robotic MV repair can contribute to precise valve inspection and operative procedures. This approach seems feasible for complex rheumatic MV disease particularly in young patients.

    View details for DOI 10.1093/ehjcr/ytz240

    View details for PubMedID 32128486

    View details for PubMedCentralID PMC7047053

  • Benefits of the Modified Bicaval Anastomosis Technique for Orthotopic Heart Transplantation From a Size-Mismatched Marginal Donor. Circulation journal : official journal of the Japanese Circulation Society Kakuta, T., Fukushima, S., Shimahara, Y., Yajima, S., Kawamoto, N., Tadokoro, N., Fukushima, N., Kitamura, S., Kobayashi, J., Fujita, T. 2019; 84 (1): 61-68

    Abstract

    Size-mismatched heart transplantation (HTx) is associated with a risk of stenosis of the caval anastomosis site or low cardiac output syndrome. We developed a modified bicaval anastomosis technique (mBCAT) that achieved an adjustable caval anastomosis to compensate for size mismatch. This study was performed to validate the rationale of the mBCAT for size-mismatched HTx.Methods and Results:This institutional consecutive series involved 106 patients who underwent HTx with the mBCAT during an 18-year period. The cohort was divided into 3 groups according to the donor-to-recipient body weight ratio: <0.8, undersized group (n=17); 0.8-1.3, size-matched group (n=68); and >1.3, oversized group (n=21); outcomes were compared. The undersized, size-matched, and oversized groups showed no significant differences in the rate of mild or worse echocardiographic tricuspid regurgitation at 1 month [1 (5.8%), 7 (10.2%), and 1 (4.8%), respectively; P=0.87] or the survival rate at 10 years [100%, 93.9%, and 100%, respectively; P=0.25]. The right heart catheter study revealed no pressure gradient across the orifices of both cavae in any patient. Additionally, the cardiac index immediately post-HTx was significantly low in the undersized group (P=0.008), but was similar to the other groups at 6 months post-HTx (P=0.16).The mBCAT prevented caval anastomosis-related complications in size-mismatched HTx and achieved excellent hemodynamics regardless of donor size.

    View details for DOI 10.1253/circj.CJ-19-0441

    View details for PubMedID 31801926

  • Three-dimensional simulation for left ventricular assist device implantation in a small patient with chest wall deformity. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Yajima, S., Toda, K., Tsukiya, T., Sawa, Y. 2019; 55 (4): 788-789

    Abstract

    The rate of patients requiring left ventricular assist device (LVAD) implantation remains at a pace exceeding 2000 per year worldwide. Children and small adult patients, with a body surface area <1.5 m2, are at a disadvantage for receiving an implantable LVAD because of its large pump size. Preoperative simulation of the results of various LVAD implantation methods and devices in such challenging cases will be helpful for surgeons. Herein, we introduce a preoperative LVAD simulation method using image processing software and present a case in which we obtained satisfactory results.

    View details for DOI 10.1093/ejcts/ezy309

    View details for PubMedID 30189028

  • Tumorigenicity assay essential for facilitating safety studies of hiPSC-derived cardiomyocytes for clinical application. Scientific reports Ito, E., Miyagawa, S., Takeda, M., Kawamura, A., Harada, A., Iseoka, H., Yajima, S., Sougawa, N., Mochizuki-Oda, N., Yasuda, S., Sato, Y., Sawa, Y. 2019; 9 (1): 1881

    Abstract

    Transplantation of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC-CMs) is a promising treatment for heart failure, but residual undifferentiated hiPSCs and malignant transformed cells may lead to tumor formation. Here we describe a highly sensitive tumorigenicity assay for the detection of these cells in hiPSC-CMs. The soft agar colony formation assay and cell growth analysis were unable to detect malignantly transformed cells in hiPSC-CMs. There were no karyotypic abnormalities during hiPSCs subculture and differentiation. The hiPSC markers TRA1-60 and LIN28 showed the highest sensitivity for detecting undifferentiated hiPSCs among primary cardiomyocytes. Transplantation of hiPSC-CMs with a LIN28-positive fraction > 0.33% resulted in tumor formation in nude rats, whereas no tumors were formed when the fraction was < 0.1%. These findings suggested that combination of these in vitro and in vivo tumorigenecity assays can verify the safety of hiPSC-CMs for cell transplantation therapy.

    View details for DOI 10.1038/s41598-018-38325-5

    View details for PubMedID 30760836

    View details for PubMedCentralID PMC6374479

  • Cell Spray Transplantation of Adipose-derived Mesenchymal Stem Cell Recovers Ischemic Cardiomyopathy in a Porcine Model. Transplantation Mori, D., Miyagawa, S., Yajima, S., Saito, S., Fukushima, S., Ueno, T., Toda, K., Kawai, K., Kurata, H., Nishida, H., Isohashi, K., Hatazawa, J., Sawa, Y. 2018; 102 (12): 2012-2024

    Abstract

    Allogeneic adipose-derived mesenchymal stem cells (ADSC) are promising cell sources for cell therapy to treat ischemic cardiomyopathy (ICM). We hypothesized that ADSC transplantation via the new cell spray method may be a feasible, safe, and effective treatment for ICM.Human ADSCs were acquired from white adipose tissue. Porcine ICM models were established by constriction of the left anterior descending coronary artery. Adipose-derived mesenchymal stem cells were spread over the surface of the heart via cell spray in fibrinogen and thrombin solutions. The cardiac function was compared with that of the control group.Adipose-derived mesenchymal stem cells were successfully transplanted forming a graft-like gel film covering the infarct myocardium. Premature ventricular contractions were rarely detected in the first 3 days after transplantation. Echocardiography and magnetic resonance imaging revealed improved cardiac performance of the ADSC group at 4 and 8 weeks after transplantation. Systolic and diastolic parameters were significantly greater in the ADSC group at 8 weeks after transplantation. Histological examination showed significantly attenuated left ventricular remodeling and a greater vascular density in the infarct border area in the ADSC group. Moreover, the coronary flow reserve was maintained, and expression levels of angiogenesis-related factors in the infarct border and remote areas were significantly increased.Spray method implantation of allogenic ADSCs can improve recovery of cardiac function in a porcine infarction model. This new allogenic cell delivery system may help to resolve current limitations of invasiveness and cost in stem cell therapy.

    View details for DOI 10.1097/TP.0000000000002385

    View details for PubMedID 30048399

  • Development of a vitrification method for preserving human myoblast cell sheets for myocardial regeneration therapy. BMC biotechnology Ohkawara, H., Miyagawa, S., Fukushima, S., Yajima, S., Saito, A., Nagashima, H., Sawa, Y. 2018; 18 (1): 56

    Abstract

    Tissue-engineered cardiac constructs have potential in the functional recovery of heart failure; however, the preservation of these constructs is crucial for the development and widespread application of this treatment. We hypothesized that tissue-engineered skeletal myoblast (SMB) constructs may be preserved by vitrification to conserve biological function and structure.Scaffold-free cardiac cell-sheet constructs were prepared from SMBs and immersed in a vitrification solution containing ethylene glycol, sucrose, and carboxyl poly-L-lysine. The cell sheet was wrapped in a thin film and frozen rapidly above liquid nitrogen to achieve vitrification (vitrification group, n = 8); fresh, untreated SMB sheets (fresh group, n = 8) were used as the control. The cryopreserved SMB sheets were thawed at 2 days, 1 week, 1 month, and 3 months after cryopreservation for assessment. Thawed, cryopreserved SMB sheets were transplanted into rat hearts in a myocardial infarction nude rat model, and their effects on cardiac function were evaluated. Cell viability in the cardiac constructs of the vitrification group was comparable to that of the fresh group, independent of the period of cryopreservation (p > 0.05). The structures of the cell-sheet constructs, including cell-cell junctions such as desmosomes, extracellular matrix, and cell membranes, were maintained in the vitrification group for 3 months. The expression of cytokine genes and extracellular matrix proteins (fibronectin, collagen I, N-cadherin, and integrin α5) showed similar levels in the vitrification and fresh groups. Moreover, in an in vivo experiment, the ejection fraction was significantly improved in animals treated with the fresh or cryopreserved constructs as compared to that in the sham-treated group (p < 0.05).Overall, these results show that the vitrification method proposed here preserves the functionality and structure of scaffold-free cardiac cell-sheet constructs using human SMBs after thawing, suggesting the potential clinical application of this method in cell-sheet therapy.

    View details for DOI 10.1186/s12896-018-0467-5

    View details for PubMedID 30200961

    View details for PubMedCentralID PMC6131806

  • Multiple coronary stenting negatively affects myocardial recovery after coronary bypass grafting. General thoracic and cardiovascular surgery Yajima, S., Yoshioka, D., Fukushima, S., Toda, K., Miyagawa, S., Yoshikawa, Y., Hata, H., Saito, S., Domae, K., Sawa, Y. 2018; 66 (8): 446-455

    Abstract

    We aimed to elucidate the relationship between the magnitude of myocardial recovery after coronary artery bypass grafting (CABG) and the prognosis and to explore the predictors of myocardial non-recovery.Eighty-one patients with a preoperative left ventricular ejection fraction (LVEF) ≤ 40% who underwent isolated CABG between 2002 and 2015 and had undergone echocardiographic follow-up (median follow-up, 3.1 years; interquartile range 1.2-6.0 years) were analyzed. The Recovery group comprised patients with LVEF improvement ≥ 10%, whereas the Non-recovery group comprised those with an LVEF improvement < 10%. Group differences in overall survival, freedom from major adverse cardiac events (MACEs), and readmission due to heart failure were evaluated. In addition, the risk factors for LVEF non-recovery were evaluated in a multivariate analysis.A total of 39 patients (48%) were in the Recovery group, whereas 42 patients (52%) were in the Non-recovery group. Although the survival and freedom from MACE rates were comparable, the rate of freedom from heart failure requiring hospitalization at 1, 5, and 8 years of follow-up was significantly lower in the Non-recovery group than in the Recovery group (p = 0.012). A history of percutaneous coronary intervention (PCI) was an exclusive independent risk factor for post-CABG myocardial non-recovery (odds ratio, 16.0; 95% confidence interval, 3.44-125). Furthermore, the number of coronary stents was negatively correlated with LVEF recovery (r = - 0.460, p = 0.024).Great consideration should be taken when performing CABG in patients with left ventricular dysfunction and a history of PCI, particularly in those with multiple coronary stents.

    View details for DOI 10.1007/s11748-018-0937-7

    View details for PubMedID 29761271

  • Definitive Determinant of Late Significant Tricuspid Regurgitation After Aortic Valve Replacement. Circulation journal : official journal of the Japanese Circulation Society Yajima, S., Yoshioka, D., Toda, K., Fukushima, S., Miyagawa, S., Yoshikawa, Y., Saito, S., Domae, K., Ueno, T., Kuratani, T., Sawa, Y. 2018; 82 (3): 886-894

    Abstract

    Uncertainties remain regarding the course of existing tricuspid regurgitation (TR) after aortic valve replacement (AVR), and its long-term impact on outcome. We investigated changes in existing TR after isolated AVR for severe aortic stenosis (AS), the impact of preoperative TR on long-term outcome, and predictors of late significant TR.Methods and Results:After excluding mild mitral regurgitation and severe TR, 226 consecutive patients undergoing isolated AVR for severe AS between 2002 and 2015 were reviewed. Patients were classified into a non-TR (none/trivial preoperative TR, n=159) and a TR group (mild/moderate preoperative TR, n=67). During follow-up (median, 4.3 years), late significant TR was more prevalent in the TR group (n=20; 35.0%) than in the non-TR group (n=13; 9.6%; HR, 10.0; 95% CI: 4.44-24.7; P<0.001). The TR group developed more right heart failure (n=3; 5% vs. no patients in the non-TR group, P=0.007), and had a decreased estimated glomerular filtration rate (relative to baseline) until 5 years postoperatively. The tricuspid annulus diameter index was an independent predictor of late significant TR development.Preoperative mild or moderate TR is aggravated after isolated AVR, resulting in a high incidence of renal dysfunction and right heart failure. Concomitant tricuspid valve intervention should be considered in patients undergoing AVR for severe AS with mild or moderate TR accompanied by dilated tricuspid annulus.

    View details for DOI 10.1253/circj.CJ-17-0996

    View details for PubMedID 29238013

  • Pivotal Role of Non-cardiomyocytes in Electromechanical and Therapeutic Potential of Induced Pluripotent Stem Cell-Derived Engineered Cardiac Tissue. Tissue engineering. Part A Iseoka, H., Miyagawa, S., Fukushima, S., Saito, A., Masuda, S., Yajima, S., Ito, E., Sougawa, N., Takeda, M., Harada, A., Lee, J. K., Sawa, Y. 2018; 24 (3-4): 287-300

    Abstract

    Although engineered cardiac tissues (ECTs) derived from induced pluripotent stem cells (iPSCs) are promising for myocardial regenerative therapy, the appropriate ratio of cardiomyocytes to non-cardiomyocytes is not fully understood. Here, we determined whether ECT-cell content is a key determinant of its structure/function, thereby affecting ECT therapeutic potential for advanced heart failure. Scaffold-free ECTs containing different ratios (25%, 50%, 70%, or 90%) of iPSC-derived cardiomyocytes were generated by magnetic-activated cell sorting by using cardiac-specific markers. Notably, ECTs showed synchronized spontaneous beating when cardiomyocytes constituted ≥50% of total cells, with the electrical-conduction velocity increasing depending on cardiomyocyte ratio; however, ECTs containing 90% cardiomyocytes failed to form stable structures. ECTs containing 25% or 50% cardiomyocytes predominantly expressed collagen and fibronectin, whereas ECTs containing 70% cardiomyocytes predominantly expressed laminin and exhibited the highest contractile/relaxation properties. Furthermore, transplantation of ECTs containing 50% or 70% cardiomyocytes into a rat chronic myocardial infarction model led to a more profound functional recovery as compared with controls. Notably, transplanted ECTs showed electrical synchronization with the native heart under Langendorff perfusion. Collectively, these results indicate that the quantity of non-cardiomyocytes is critical in generating functional iPSC-derived ECTs as grafts for cardiac-regeneration therapy, with ECTs containing 50-70% cardiomyocytes exhibiting stable structures and increased cardiotherapeutic potential.

    View details for DOI 10.1089/ten.TEA.2016.0535

    View details for PubMedID 28498040

    View details for PubMedCentralID PMC5792250

  • Human Pluripotent Stem Cell-Derived Cardiac Tissue-like Constructs for Repairing the Infarcted Myocardium. Stem cell reports Li, J., Minami, I., Shiozaki, M., Yu, L., Yajima, S., Miyagawa, S., Shiba, Y., Morone, N., Fukushima, S., Yoshioka, M., Li, S., Qiao, J., Li, X., Wang, L., Kotera, H., Nakatsuji, N., Sawa, Y., Chen, Y., Liu, L. 2017; 9 (5): 1546-1559

    Abstract

    High-purity cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) are promising for drug development and myocardial regeneration. However, most hiPSC-derived CMs morphologically and functionally resemble immature rather than adult CMs, which could hamper their application. Here, we obtained high-quality cardiac tissue-like constructs (CTLCs) by cultivating hiPSC-CMs on low-thickness aligned nanofibers made of biodegradable poly(D,L-lactic-co-glycolic acid) polymer. We show that multilayered and elongated CMs could be organized at high density along aligned nanofibers in a simple one-step seeding process, resulting in upregulated cardiac biomarkers and enhanced cardiac functions. When used for drug assessment, CTLCs were much more robust than the 2D conventional control. We also demonstrated the potential of CTLCs for modeling engraftments in vitro and treating myocardial infarction in vivo. Thus, we established a handy framework for cardiac tissue engineering, which holds high potential for pharmaceutical and clinical applications.

    View details for DOI 10.1016/j.stemcr.2017.09.007

    View details for PubMedID 29107590

    View details for PubMedCentralID PMC5829319

  • Intravenous retro-uterine echographic surveillance of the foetus during surgical thrombectomy for life-threatening pulmonary thromboembolism. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Yajima, S., Saito, S., Toda, K., Sawa, Y. 2017; 52 (5): 995-997

    Abstract

    Pulmonary thromboembolism is a life-threatening disease, particularly during pregnancy. We report a case of successful cardiopulmonary resuscitation followed by surgical thrombectomy in a 35-year-old woman at 28 weeks of gestation. Intracardiac echocardiography was percutaneously located behind the uterus, and greatly assisted monitoring of the foetal condition and haemodynamic status.

    View details for DOI 10.1093/ejcts/ezx206

    View details for PubMedID 28605430

  • Redo coronary bypass grafting for congenital left main coronary atresia: a case report. Journal of cardiothoracic surgery Yajima, S., Toda, K., Nishi, H., Yoshioka, D., Nakamura, T., Miyagawa, S., Yoshikawa, Y., Fukushima, S., Sawa, Y. 2017; 12 (1): 26

    Abstract

    Congenital left main coronary atresia is an extremely rare coronary anomaly. Long-term surgical outcomes and the optimal management strategies for recurrence of ischemia remain uncertain. Herein, we present a case involving successful redo coronary artery bypass grafting for unstable angina 27 years after the initial coronary artery bypass grafting for congenital left main coronary atresia.A 33-year-old woman was referred to our department with unstable angina. At the age of 6, she had undergone coronary artery bypass grafting of the second diagonal branch using the left internal thoracic artery and the obtuse marginal branch using saphenous vein grafting for left main coronary atresia. Although a coronary angiogram showed a patent left internal thoracic artery graft to the second diagonal branch and a patent saphenous vein graft to the obtuse marginal branch, the left anterior descending artery was not being perfused by the grafts because of a disruption of blood flow to the left anterior descending artery from the left internal thoracic artery. Therefore, we performed a redo coronary artery bypass grafting using the in situ right internal thoracic artery to the first diagonal branch, which was to be connected to the left anterior descending artery, resulting in amelioration of the ischemia of the left anterior wall. The patient was discharged 10 days after the operation and has been in good health for over 3 years without recurrence of chest symptoms.Coronary revascularization using a saphenous vein and left internal thoracic artery grafts is effective in achieving an adequate blood supply to the distal coronary arteries, and this effect can last for decades. However, careful follow-up is necessary because recurrent myocardial ischemia due to the development of a coronary artery occlusion may occur in adulthood.

    View details for DOI 10.1186/s13019-017-0588-2

    View details for PubMedID 28506276

    View details for PubMedCentralID PMC5433066

  • Symptomatic peripheral artery disease is associated with decreased long-term survival after coronary artery bypass: a contemporary retrospective analysis. Surgery today Nakamura, T., Toda, K., Miyagawa, S., Yoshikawa, Y., Fukushima, S., Saito, S., Yoshioka, D., Yajima, S., Yoshida, S., Sawa, Y. 2016; 46 (11): 1334-40

    Abstract

    Little has been documented about whether the severity of peripheral artery disease (PAD) affects the postoperative outcomes of coronary artery bypass grafting (CABG).We performed a retrospective analysis of 683 patients who underwent isolated CABG, comparing preoperative profiles and postoperative outcomes between patients with PAD (n = 116) and those without PAD (n = 567). Kaplan-Meier analysis was done to examine the long-term survival and the Cox proportional hazard model was used to establish the preoperative risk factors associated with survival.The PAD patients were older and had more preoperative comorbidities than those without PAD. There were three operative deaths in each group (p = 0.07). The patients with PAD had more postoperative complications related to transfusion requirement (p = 0.004), the need for re-exploration for bleeding (p = 0.04), longer ventilation time (p < 0.001), and longer ICU stay (p = 0.001), than those without PAD. The 10-year survival rate of the PAD patients was lower than that of the non-PAD patients (p < 0.001). Univariate and multivariate analyses revealed that symptomatic PAD (p = 0.008) was associated with decreased long-term survival.Symptomatic PAD was found to be an independent factor for poor long-term survival after CABG. Thus, aggressive screening measures for coronary disease, early surgical revascularization, and secondary prevention may improve the early and long-term outcomes of these patients.

    View details for DOI 10.1007/s00595-016-1379-4

    View details for PubMedID 27444027

  • Bilateral internal thoracic artery grafting via T-shaped partial sternotomy in a patient with terminal tracheostoma. Journal of cardiac surgery Yajima, S., Tsutsumi, Y., Monta, O., Uenaka, H., Ohashi, H. 2016; 31 (11): 690-691

    View details for DOI 10.1111/jocs.12845

    View details for PubMedID 27611225

  • Total arch replacement for a subacute type A dissection in a patient with a terminal tracheostoma after total laryngectomy: report of a case. Surgery today Yoshioka, D., Takahashi, T., Suhara, H., Higuchi, T., Sijo, T., Yajima, S., Ishizaka, T., Satoh, H. 2012; 42 (8): 785-7

    Abstract

    Standard full median sternotomy for total arch replacement in tracheostomy patients may lead to mediastinitis and graft infection. Several approaches for typical cardiac surgery, including a T-shaped sternotomy, have been used in patients with both terminal and transient tracheostomas; however, these procedures offer inadequate surgical exposure of the arch vessels. We herein report the case of a 67-year-old man with a subacute type A aortic dissection with a terminal tracheostoma after total laryngectomy, who successfully underwent total arch replacement by a fourth intercostal thoracotomy performed using an anterior bilateral approach and the arch-first technique. To our knowledge, this is the first report of a case of total arch replacement in a patient with subacute aortic dissection and a terminal tracheostoma.

    View details for DOI 10.1007/s00595-011-0071-y

    View details for PubMedID 22127538