Springer Science and Business Media LLC Acta Medica Okayama 0910-8327 2025 Outcomes of ultra-high-pressure balloon angioplasty for congenital heart disease in single-center experience EN Maiko Kondo Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kurita Department of Pediatrics, Okayama University Hospital Yosuke Fukushima Department of Pediatrics, Okayama University Hospital Yusuke Shigemitsu Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenta Hirai Department of Pediatrics, Okayama University Hospital Yuya Kawamoto Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mayuko Hara Department of Pediatrics, Okayama University Hospital Tomoyuki Kanazawa Department of Pediatric Anesthesiology, Okayama University Hospital Tatsuo Iwasaki Department of Pediatric Anesthesiology, Okayama University Hospital Yasuhiro Kotani Department of Cardiovascular Surgery, Okayama University Hospital Shingo Kasahara Department of Cardiovascular Surgery, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Hospital Kenji Baba Department of Pediatrics, Okayama University Hospital Angioplasty using ultra-high-pressure (UHP) balloons may successfully treat stenotic lesions refractory to high-pressure dilation. The use of UHP balloons in patients with congenital heart disease is mostly for dilation of the pulmonary artery, and there have been few reports on the effectiveness and safety of balloons for other sites. We retrospectively evaluated the efficacy and safety of the ultra-high-pressure balloon angioplasty (UHP-BA) for stenotic lesions in patients with congenital heart disease between January 2020 and December 2022 at Okayama University Hospital. A total of 78 UHP-BAs were performed in 44 patients, with a median age of 6.6 years and a median weight of 17.6 kg. The balloon types used in the UHP-BAs were Yoroi® and Conquest®. UHP-BA performed 39 procedures for the pulmonary artery (PA), 24 for fenestration, 8 for SVC, 4 for shunt, and three for others. The lesion-specific acute procedural success rates for PA, Fontan fenestration, SVC, and shunt were 77%, 75%, 88%, and 75%, respectively. A complication of UHP-BA occurred in 3.8% (3/78). Two of the three patients had pulmonary hemorrhage, and the remaining patients had pulmonary artery embolization due to the migration of a thrombus. There were no fatal complications. Balloon dilation with UHP balloons was safe and effective not only for pulmonary artery stenotic lesions but also for SVC, Fontan fenestration, shunt, and other dilation sites in patients with congenital heart disease. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2047-9980 13 22 2024 Eight-Year Outcomes of Cardiosphere-Derived Cells in Single Ventricle Congenital Heart Disease e038137 EN Kenta Hirai Department of Pediatrics Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryusuke Sawada Department of Pharmacology Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomohiro Hayashi Department of Pediatrics Kurashiki Central Hospital Toru Araki Department of Pediatrics National Hospital Organization Fukuyama Medical Center Naomi Nakagawa Department of Pediatric Cardiology Hiroshima City Hiroshima Citizens Hospital Maiko Kondo Department of Pediatrics Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenji Yasuda Department of Pediatrics Shimane University Faculty of Medicine Takuya Hirata Department of Pediatrics Kyoto University Graduate School of Medicine Tomoyuki Sato Department of Pediatrics Jichi Medical University Yuki Nakatsuka Department of Data Science, Center for Innovative Clinical Medicine Okayama University Hospital Michihiro Yoshida Department of Data Science, Center for Innovative Clinical Medicine Okayama University Hospital Shingo Kasahara Department of Cardiovascular Surgery Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenji Baba Department of Pediatrics Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hidemasa Oh Department of Regenerative Medicine, Center for Innovative Clinical Medicine Okayama University Hospital the TICAP/PERSEUS Study Group Background: Cardiosphere�]derived cell (CDC) infusion was associated with better clinical outcomes at 2 years in patients with single ventricle heart disease. The current study investigates time�]to�]event outcomes at 8 years.<br> Methods and Results: This cohort enrolled patients with single ventricles who underwent stage 2 or stage 3 palliation from January 2011 to January 2015 at 8 centers in Japan. The primary outcomes were time�]dependent CDC treatment effects on death and late complications during 8 years of follow�]up, assessed by restricted mean survival time. Among 93 patients enrolled (mean age, 2.3�}1.3 years; 56% men), 40 received CDC infusion. Overall survival for CDC�]treated versus control patients did not differ at 8 years (hazard ratio [HR], 0.60 [95% CI, 0.21–1.77]; P=0.35). Treatment effect had nonproportional hazards for death favoring CDCs at 4 years (restricted mean survival time difference +0.33 years [95% CI, 0.01–0.66]; P=0.043). In patients with heart failure with reduced ejection fraction, CDC treatment effect on survival was greater over 8 years (restricted mean survival time difference +1.58 years [95% CI, 0.05–3.12]; P=0.043). Compared with control participants, CDC�]treated patients showed lower incidences of late failure (HR, 0.45 [95% CI, 0.21–0.93]; P=0.027) and adverse events (subdistribution HR, 0.50 [95% CI, 0.27–0.94]; P=0.036) at 8 years.<br> Conclusions: By 8 years, CDC infusion was associated with lower hazards of late failure and adverse events in single ventricle heart disease. CDC treatment effect on survival was notable by 4 years and showed a durable clinical benefit in patients with heart failure with reduced ejection fraction over 8 years.<br> Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01273857 and NCT01829750. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0172-0643 46 6 2024 Pulmonary Flow Management by Combination Therapy of Hemostatic Clipping and Balloon Angioplasty for Right Ventricular-Pulmonary Artery Shunt in Hypoplastic Left Heart Syndrome 1635 1642 EN Yusuke Shigemitsu Department of Pediatrics, Okayama University Hospital Maiko Kondo Department of Pediatrics, Okayama University Hospital Yoshihiko Kurita Department of Pediatrics, Okayama University Hospital Yosuke Fukushima Department of Pediatrics, Okayama University Hospital Yuya Kawamoto Department of Pediatrics, Okayama University Hospital Kenta Hirai Department of Pediatrics, Okayama University Hospital Mayuko Hara Department of Pediatrics, Okayama University Hospital Tomoyuki Kanazawa Department of Pediatric Anesthesiology, Okayama University Hospital Tatsuo Iwasaki Department of Pediatric Anesthesiology, Okayama University Hospital Shingo Kasahara Department of Pediatric Anesthesiology, Okayama University Hospital Koichi Kataoka Department of Cardiovascular Surgery, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Hospital Kenji Baba Department of Pediatrics, Okayama University Hospital Controlling pulmonary blood flow in patients who have undergone Norwood palliation, especially early postoperatively, is challenging due to a change in the balance of systemic and pulmonary vascular resistance. We applied a combination therapy of clipping and balloon angioplasty for right ventricle�\pulmonary artery (RV-PA) shunt to control pulmonary blood flow, but the influence of the combination therapy on the PA condition is uncertain. Retrospectively analysis was conducted of all infants with hypoplastic left heart syndrome who had undergone Norwood palliation with RV-PA shunt at Okayama University Hospital from January 2008 to September 2022. A total of 50 consecutive patients underwent Norwood palliation with RV-PA shunt in this study period. Of them, 29 patients underwent RV-PA shunt flow clipping, and the remaining 21 had unclipped RV-PA shunt. Twenty-three patients underwent balloon angioplasty for RV-PA shunt with clips. After balloon angioplasty, oxygen saturation significantly increased from 69 (59–76)% to 80 (72–86)% (p < 0.001), and the narrowest portion of the clipped conduit significantly improved from 2.8 (1.8–3.4) to 3.8 (2.9–4.6) mm (p < 0.001). In cardiac catheterizations prior to Bidirectional cavo-pulmonary shunt (BCPS), there were no significant differences in pulmonary-to-systemic flow ratio (Qp/Qs), ventricular end-diastolic pressure, Nakata index, arterial saturation, mean pulmonary artery pressure and pulmonary vascular resistance index. On the other hand, in Cardiac catheterizations prior to Fontan, Nakata index was larger in the clipped group (p = 0.02). There was no statistically significant difference in the 5-year survival between the two groups (clipped group 96%, unclipped group 74%, log-rank test: p = 0.13). At least, our combination therapy of clipping and balloon angioplasty for RV-PA shunt did not negatively impact PA growth. Although there is a trend toward better but not statistically significant difference in outcomes in the clipped group compared to the non-clipped group, this treatment strategy may play an important role in improving outcomes in hypoplastic left heart syndrome. No potential conflict of interest relevant to this article was reported.

American Association for the Advancement of Science Acta Medica Okayama 1946-6234 12 573 2020 Cardiosphere-derived exosomal microRNAs for myocardial repair in pediatric dilated cardiomyopathy eabb3336 EN Kenta Hirai Department of Pediatric Cardiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Daiki Ousaka Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yosuke Fukushima Department of Pediatric Cardiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Maiko Kondo Department of Pediatric Cardiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takahiro Eitoku Department of Pediatric Cardiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yusuke Shigemitsu Department of Pediatric Cardiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mayuko Hara Department of Pediatric Cardiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenji Baba Department of Pediatric Cardiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tatsuo Iwasaki Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shingo Kasahara Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinichi Ohtsuki Department of Pediatric Cardiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hidemasa Oh Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital Although cardiosphere-derived cells (CDCs) improve cardiac function and outcomes in patients with single ventricle physiology, little is known about their safety and therapeutic benefit in children with dilated cardiomyopathy (DCM). We aimed to determine the safety and efficacy of CDCs in a porcine model of DCM and translate the preclinical results into this patient population. A swine model of DCM using intracoronary injection of microspheres created cardiac dysfunction. Forty pigs were randomized as preclinical validation of the delivery method and CDC doses, and CDC-secreted exosome (CDCex)–mediated cardiac repair was analyzed. A phase 1 safety cohort enrolled five pediatric patients with DCM and reduced ejection fraction to receive CDC infusion. The primary endpoint was to assess safety, and the secondary outcome measure was change in cardiac function. Improved cardiac function and reduced myocardial fibrosis were noted in animals treated with CDCs compared with placebo. These functional benefits were mediated via CDCex that were highly enriched with proangiogenic and cardioprotective microRNAs (miRNAs), whereas isolated CDCex did not recapitulate these reparative effects. One-year follow-up of safety lead-in stage was completed with favorable profile and preliminary efficacy outcomes. Increased CDCex-derived miR-146a-5p expression was associated with the reduction in myocardial fibrosis via suppression of proinflammatory cytokines and transcripts. Collectively, intracoronary CDC administration is safe and improves cardiac function through CDCex in a porcine model of DCM. The safety lead-in results in patients provide a translational framework for further studies of randomized trials and CDCex-derived miRNAs as potential paracrine mediators underlying this therapeutic strategy. No potential conflict of interest relevant to this article was reported.

Lippincott Williams & Wilkins Acta Medica Okayama 00097330 116 4 2015 Intracoronary Autologous Cardiac Progenitor Cell Transfer in Patients With Hypoplastic Left Heart Syndrome (TICAP) : A Prospective Phase 1 Controlled Trial 653 664 EN Shuta Ishigami Departments of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinichi Ohtsuki Departments of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Suguru Tarui Departments of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Daiki Ousaka Departments of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takahiro Eitoku Departments of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Maiko Kondo Departments of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Michihiro Okuyama Departments of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Junko Kobayashi Departments of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenji Baba Departments of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Sadahiko Arai Departments of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takuya Kawabata Departments of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ko Yoshizumi Departments of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Atsushi Tateishi Departments of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yosuke Kuroko Departments of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tatsuo Iwasaki Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shuhei Sato Department of Radilogy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shingo Kasahara Departments of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shunji Sano Departments of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hidemasa Oh Department of Regeneraive Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital RATIONALE: Hypoplastic left heart syndrome (HLHS) remains a lethal congenital cardiac defect. Recent studies have suggested that intracoronary administration of autologous cardiosphere-derived cells (CDCs) may improve ventricular function. OBJECTIVE: The aim of this study was to test whether intracoronary delivery of CDCs is feasible and safe in patients with hypoplastic left heart syndrome. METHODS AND RESULTS: Between January 5, 2011, and January 16, 2012, 14 patients (1.8�}1.5 years) were prospectively assigned to receive intracoronary infusion of autologous CDCs 33.4�}8.1 days after staged procedures (n=7), followed by 7 controls with standard palliation alone. The primary end point was to assess the safety, and the secondary end point included the preliminary efficacy to verify the right ventricular ejection fraction improvements between baseline and 3 months. Manufacturing and intracoronary delivery of CDCs were feasible, and no serious adverse events were reported within the 18-month follow-up. Patients treated with CDCs showed right ventricular ejection fraction improvement from baseline to 3-month follow-up (46.9%�}4.6% to 52.1%�}2.4%; P=0.008). Compared with controls at 18 months, cardiac MRI analysis of CDC-treated patients showed a higher right ventricular ejection fraction (31.5%�}6.8% versus 40.4%�}7.6%; P=0.049), improved somatic growth (P=0.0005), reduced heart failure status (P=0.003), and lower incidence of coil occlusion for collaterals (P=0.007). CONCLUSIONS: Intracoronary infusion of autologous CDCs seems to be feasible and safe in children with hypoplastic left heart syndrome after staged surgery. Large phase 2 trials are warranted to examine the potential effects of cardiac function improvements and the long-term benefits of clinical outcomes. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1522-1946 81 5 2013 Usefulness of balloon angioplasty for the right ventricle-pulmonary artery shunt with the modified norwood procedure 837 842 EN Naoki Ohno Shinichi Ohtsuki Koichi Kataoka Kenji Baba Yoshio Okamoto Maiko Kondo Shunji Sano Shingo Kasahara Osami Honjo Tsuneo Morishima Objective We sought to evaluate the efficacy of balloon angioplasty (BA) for severely desaturated patients due to a stenotic right ventricle (RV) to pulmonary artery (PA) shunt following modified Norwood procedure. Methods Of 87 patients who underwent a Norwood procedure with the RV-PA shunt between February 1998 through March 2010, 22 (25%) patients underwent BA. The efficacy of BA was assessed by angiographic measurement of the changes in the internal diameters of the stenotic portions of the shunt, changes in arterial saturation and clinical outcomes. Results BA was performed for stenotic RV-PA shunts following stage I palliation (n = 17, 77%), or those placed as an additional blood source (n = 5, 23%, 3 patients awaiting biventricular repair, 2 patients following stage II palliation). The location of the BA was at the distal anastomosis in 12 (54.5%), proximal anastomosis in 21 (95.4%) and in the mid-portion of the shunt in 11 (50%) cases. The diameters of these three shunt portions were measured from the anteriorposterior and lateral angiographic images, increasing significantly after BA (p < 0.0001) in all. Arterial saturation significantly improved after BA in all cases (66.5 +/- 4.3% to 79.4 +/- 3.4%, p < 0.0001). Freedom from reintervention was 100%. All patients underwent subsequent elective planned surgery at an appropriate age with no mortality. Conclusions A BA-alone strategy for a stenotic RV-PA shunt was effective for all three shunt portions, minimizing shunt-related premature surgical intervention. No potential conflict of interest relevant to this article was reported.