Faculty Profiles - KASAHARA Shingo

Papers - KASAHARA Shingo

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Intracoronary Cardiac Progenitor Cells in Single Ventricle Physiology: The PERSEUS (Cardiac Progenitor Cell Infusion to Treat Univentricular Heart Disease) Randomized Phase 2 Trial. International journal

Shuta Ishigami, Shinichi Ohtsuki, Takahiro Eitoku, Daiki Ousaka, Maiko Kondo, Yoshihiko Kurita, Kenta Hirai, Yosuke Fukushima, Kenji Baba, Takuya Goto, Naohiro Horio, Junko Kobayashi, Yosuke Kuroko, Yasuhiro Kotani, Sadahiko Arai, Tatsuo Iwasaki, Shuhei Sato, Shingo Kasahara, Shunji Sano, Hidemasa Oh

Circulation research 120 ( 7 ) 1162 - 1173 2017.3

Language：English Publishing type：Research paper (scientific journal)

RATIONALE: Patients with single ventricle physiology are at high risk of mortality resulting from ventricular dysfunction. The preliminary results of the phase 1 trial showed that cardiosphere-derived cells (CDCs) may be effective against congenital heart failure. OBJECTIVE: To determine whether intracoronary delivery of autologous CDCs improves cardiac function in patients with single ventricle physiology. METHODS AND RESULTS: We conducted a phase 2 randomized controlled study to assign in a 1:1 ratio 41 patients who had single ventricle physiology undergoing stage 2 or 3 palliation to receive intracoronary infusion of CDCs 4 to 9 weeks after surgery or staged reconstruction alone (study A). The primary outcome measure was to assess improvement in cardiac function at 3-month follow-up. Four months after palliation, controls had an alternative option to receive late CDC infusion on request (study B). Secondary outcomes included ventricular function, heart failure status, somatic growth, and health-related quality of life after a 12-month observation. At 3 months, the absolute changes in ventricular function were significantly greater in the CDC-treated group than in the controls (+6.4% [SD, 5.5] versus +1.3% [SD, 3.7]; P=0.003). In study B, a late CDC infusion in 17 controls increased the ventricular function at 3 months compared with that at baseline (38.8% [SD, 7.7] versus 34.8% [SD, 7.4]; P<0.0001). At 1 year, overall CDC infusion was associated with improved ventricular function (41.4% [SD, 6.6] versus 35.0% [SD, 8.2]; P<0.0001) and volumes (P<0.001), somatic growth (P<0.0001) with increased trophic factors production, such as insulin-like growth factor-1 and hepatocyte growth factor, and quality of life, along with a reduced heart failure status (P<0.0001) and cardiac fibrosis (P=0.014) relative to baseline. CONCLUSIONS: Intracoronary infusion of CDCs after staged palliation favorably affected cardiac function by reverse remodeling in patients with single ventricle physiology. This impact may improve heart failure status, somatic growth, and quality of life in patients and reduce parenting stress for their families. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01829750.

DOI： 10.1161/CIRCRESAHA.116.310253

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HFpEF(heart failure with preserved ejection fraction)に対する心臓内幹細胞移植の有効性

逢坂大樹, 後藤拓弥, 石神修大, 佐野俊和, 平井健太, 大月審一, 笠原真悟, 佐野俊二, 王英正

日本循環器学会学術集会抄録集 81回 CP - 219 2017.3

単腔内循環は単心室の仔ブタモデルにおける心臓前駆細胞の静注送達後の細胞生着を促進する(Single Chamber Circulation Enhances Cell Engraftment after Intravenous Delivery of Cardiac Progenitor Cells in Piglet Models of Univentricular Heart)

王英正, 後藤拓弥, 逢坂大樹, 佐野俊和, 平井健太, 笠原真悟, 佐野俊二

日本循環器学会学術集会抄録集 81回 PJ - 401 2017.3

Enhanced EP4 Expression in a Pulmonary Artery Aneurysm With Dissection in a Patient With Pulmonary Arterial Hypertension. International journal

Satoshi Akagi, Kazufumi Nakamura, Utako Yokoyama, Shingo Kasahara, Toshihiro Sarashina, Kentaro Ejiri, Hiroshi Ito

Circulation. Cardiovascular imaging 10 ( 2 ) 2017.2

Treatment Outcomes for Patients with Fontan Associated Protein-losing Enteropathy

Kurita Yoshihiko, Baba Kenji, Kondo Maiko, Eitoku Takahiro, Tsukahara Hirokazu, Sano Shunji, Kasahara Shingo, Iwasaki Tatsuo, Sato Shuhei, Ohtsuki Shinichi

Pediatric Cardiology and Cardiac Surgery 33 ( 3 ) 202 - 210 2017

Language：Japanese Publisher：Japanese Society of Pediatric Cardiology and Cardiac Surgery

Background: Protein-losing enteropathy (PLE) following the Fontan operation has been an extremely difficult complication to treat successfully. This study aimed to assess the prognosis and to establish appropriate treatment strategies for PLE.Methods: From 1991 to 2014, 23 patients with PLE following the Fontan operation were identified from clinical database at Okayama University Hospital. Data were collected retrospectively.Results: A total of 401 patients underwent Fontan operation at our institution during the study period. In this cohort, the 5.7％ incidence of PLE was relative to the total number of Fontan operations. Following PLE diagnosis, patients had a 68％ and 54％ survival rate at 5 and 10 years, respectively. The causes of death included sepsis, multiple organ failure, heart failure, and intracranial bleeding. In the treatment of PLE, 23 (100％) patients were treated with medication, 10 (43％) patients underwent catheter intervention and 15 (65％) patients underwent surgery. Patients who died were older at the time of PLE diagnosis and were associated with a longer interval between the Fontan operation and PLE diagnosis. Decreased survival was observed in patients with the following conditions post-PLE treatment: a cardiac index (CI)＜2.8 L/min/mm, decreased ventricular ejection fraction (vEF)＜50％, and high central venous pressure (meanCVP)≧15 mmHg.Conclusion: Our current treatment for PLE was only partially successful. Strategies for reducing CVP and improving both CI and vEF may be effective. Further studies are necessary to determine better treatment strategies for the future.

DOI： 10.9794/jspccs.33.202

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A staged decompression of right ventricle allows growth of right ventricle and subsequent biventricular repair in patients with pulmonary atresia and intact ventricular septum. International journal

Yasuhiro Kotani, Shingo Kasahara, Yasuhiro Fujii, Takahiro Eitoku, Kenji Baba, Shin-Ichi Otsuki, Yosuke Kuroko, Sadahiko Arai, Shunji Sano

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 50 ( 2 ) 298 - 303 2016.8

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: To achieve the growth of right-sided heart structures, our choice of the first palliation for patients with pulmonary atresia and intact ventricular septum (PA-IVS) includes a modified Blalock-Taussig shunt (BTS) with pulmonary valvotomy. We sought to analyse the impact of the first palliation on the growth of right-sided heart structures and factors associated with a choice of definitive surgical procedure. METHODS: Fifty patients with PA-IVS who underwent a staged surgical approach from 1991 to 2012 were retrospectively reviewed. RESULTS: Right ventricular (RV)-coronary artery fistulas were seen in 42% of patients at the time of birth. All 50 patients had a modified BTS with pulmonary valvotomy. Six patients died after the first palliation or inter-stage. Thirty patients achieved a biventricular repair (BVR group), 6 patients had a 1 + 1/2 ventricular repair (1 + 1/2V group) and 5 patients had a Fontan completion (Fontan group). After modified BTS with pulmonary valvotomy, tricuspid valve z-score did not increase in any of the group (BVR: pre -2.79 vs post -2.24, 1 + 1/2V: pre -5.25 vs post -6.69, Fontan: pre -6.82 vs post -7.94). Normalized RV end-diastolic volume increased only in BVR group after modified BTS with pulmonary valvotomy (BVR: pre 32% vs post 64%, 1 + 1/2V: pre 43% vs post 42%, Fontan: pre 29% vs post 32%). Major RV-coronary artery fistula was a strong factor with proceeding single-ventricle palliation [BVR: 4/30 (13%) patients, 1 + 1/2V: 1/6 (17%) and Fontan: 4/5 (80%)]. CONCLUSIONS: Tricuspid valve growth was not obtained by modified BTS with pulmonary valvotomy; therefore, tricuspid valve size at birth appeared to be a predictor for achieving BVR. Proportionate RV growth was seen only in patients who achieved BVR. However, RV growth was not seen in patients having 1 + 1/2 ventricular repair. Major RV-coronary artery fistula was a strong predictor for proceeding single-ventricle palliation.

DOI： 10.1093/ejcts/ezw124

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小児インターベンション心臓病学の近年の進歩研究からカテーテルラボへ単心室血行動態を持つ小児に対する自己cardiosphere derived cellの冠動脈内注入療法(Intracoronary Infusion of Autologous Cardiosphere Derived Cells for Single Ventricle Physiology Children)

栄徳隆裕, 大月審一, 馬場健児, 近藤麻衣子, 栗田佳彦, 福嶋遥佑, 重光祐輔, 平井健太, 王英正, 佐野俊二, 笠原真悟

日本小児循環器学会雑誌 32 ( Suppl.1 ) s1 - 103 2016.7

単心室循環の血行動態に着目した経静脈的細胞投与による心筋再生医療の新たな可能性

後藤拓弥, 逢坂大樹, 石神修大, 平井健太, 高橋生, 笠原真悟, 佐野俊二, 王英正

日本小児循環器学会雑誌 32 ( Suppl.1 ) s1 - 353 2016.7

A prospective randomized trial comparing the clinical effectiveness and biocompatibility of heparin-coated circuits and PMEA-coated circuits in pediatric cardiopulmonary bypass. International journal

Hideshi Itoh, Shingo Ichiba, Yoshihito Ujike, Takuma Douguchi, Shingo Kasahara, Sadahiko Arai, Shunji Sano

Perfusion 31 ( 3 ) 247 - 54 2016.4

Language：English Publishing type：Research paper (scientific journal)

OBJECT: We compared the clinical effectiveness and biocompatibility of poly-2-methoxyethyl acrylate (PMEA)-coated and heparin-coated cardiopulmonary bypass (CPB) circuits in a prospective pediatric trial. METHODS: Infants randomly received heparin-coated (n=7) or PMEA-coated (n=7) circuits in elective pediatric cardiac surgery with CPB for ventricular septum defects. Clinical and hematologic variables, respiratory indices and hemodynamic changes were analyzed perioperatively. RESULTS: Demographic and clinical variables were similar in both groups. Leukocyte counts were significantly lower 5 minutes after CPB in the PMEA group than the heparin group. Hemodynamic data showed that PMEA caused hypotension within 5 minutes of CPB. The respiratory index was significantly higher immediately after CPB and 1 hour after transfer to the intensive care unit (ICU) in the PMEA group, as were levels of C-reactive protein 24 hours after transfer to the ICU. CONCLUSION: Our study shows that PMEA-coated circuits, unlike heparin-coated circuits, cause transient leukopenia during pediatric CPB and, perhaps, systemic inflammatory respiratory syndrome after pediatric CPB.

DOI： 10.1177/0267659115598217

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ECMOが必要であったtachycardia induced cardiomyopathyの1例

枝木大治, 小松弘明, 佐野俊和, 木村紘爾, 堀尾直裕, 小林純子, 衛藤弘城, 黒子洋介, 小谷恭弘, 新井禎彦, 笠原真悟, 佐野俊二

岡山医学会雑誌 128 ( 1 ) 81 - 82 2016.4

Effect of the Pulsatile Extracorporeal Membrane Oxygenation on Hemodynamic Energy and Systemic Microcirculation in a Piglet Model of Acute Cardiac Failure. International journal

Hideshi Itoh, Shingo Ichiba, Yoshihito Ujike, Takuma Douguchi, Hideaki Obata, Syuji Inamori, Tatsuo Iwasaki, Shingo Kasahara, Shunji Sano, Akif Ündar

Artificial organs 40 ( 1 ) 19 - 26 2016.1

Language：English Publishing type：Research paper (scientific journal)

The objective of this study was to compare the effects of pulsatile and nonpulsatile extracorporeal membrane oxygenation (ECMO) on hemodynamic energy and systemic microcirculation in an acute cardiac failure model in piglets. Fourteen piglets with a mean body weight of 6.08 ± 0.86 kg were divided into pulsatile (N = 7) and nonpulsatile (N = 7) ECMO groups. The experimental ECMO circuit consisted of a centrifugal pump, a membrane oxygenator, and a pneumatic pulsatile flow generator system developed in-house. Nonpulsatile ECMO was initiated at a flow rate of 140 mL/kg/min for the first 30 min with normal heart beating, with rectal temperature maintained at 36°C. Ventricular fibrillation was then induced with a 3.5-V alternating current to generate a cardiac dysfunction model. Using this model, we collected the data on pulsatile and nonpulsatile groups. The piglets were weaned off ECMO at the end of the experiment (180 min after ECMO was initiated). The animals did not receive blood transfusions, inotropic drugs, or vasoactive drugs. Blood samples were collected to measure hemoglobin, methemoglobin, blood gases, electrolytes, and lactic acid levels. Hemodynamic energy was calculated using the Shepard's energy equivalent pressure. Near-infrared spectroscopy was used to monitor brain and kidney perfusion. The pulsatile ECMO group had a higher atrial pressure (systolic and mean), and significantly higher regional saturation at the brain level, than the nonpulsatile group (for both, P < 0.05). Additionally, the pulsatile ECMO group had higher methemoglobin levels within the normal range than the nonpulsatile group. Our study demonstrated that pulsatile ECMO produces significantly higher hemodynamic energy and improves systemic microcirculation, compared with nonpulsatile ECMO in acute cardiac failure.

DOI： 10.1111/aor.12588

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Anomalous right subclavian artery from pulmonary artery. International journal

Ko Yoshizumi, Shingo Kasahara, Shunji Sano

Asian cardiovascular & thoracic annals 24 ( 1 ) 115 - 115 2016.1

Transcoronary infusion of cardiac progenitor cells in hypoplastic left heart syndrome: Three-year follow-up of the Transcoronary Infusion of Cardiac Progenitor Cells in Patients With Single-Ventricle Physiology (TICAP) trial. International journal

Suguru Tarui, Shuta Ishigami, Daiki Ousaka, Shingo Kasahara, Shinichi Ohtsuki, Shunji Sano, Hidemasa Oh

The Journal of thoracic and cardiovascular surgery 150 ( 5 ) 1198 - 1207 2015.11

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: Our aim was to assess midterm safety and clinical outcomes of intracoronary infusion of cardiosphere-derived cells (CDCs) after staged palliation in patients with hypoplastic left heart syndrome (HLHS). METHODS: In this prospective, controlled study, 14 consecutive patients with HLHS who were undergoing 2- or 3-stage surgical palliations were assigned to receive intracoronary CDC infusion 1 month after cardiac surgery (n = 7), followed by 7 patients allocated to a control group with standard care alone. The primary end point was to assess procedural feasibility and safety; the secondary end point was to evaluate cardiac function and heart failure status through 36-month follow-up. RESULTS: No complications, including tumor formation, were reported within 36 months after CDC infusion. Echocardiography showed significantly greater improvement in right ventricular ejection fraction (RVEF) in infants receiving CDCs than in controls at 36 months (+8.0% ± 4.7% vs +2.2% ± 4.3%; P = .03). These cardiac function improvements resulted in reduced brain natriuretic peptide levels (P = .04), lower incidence of unplanned catheter interventions (P = .04), and higher weight-for-age z score (P = .02) at 36 months relative to controls. As independent predictors of treatment responsiveness, absolute changes in RVEF at 36 months were negatively correlated with age, weight-for-age z score, and RVEF at CDC infusion. CONCLUSIONS: Intracoronary CDC infusion after staged procedure in patients with HLHS is safe and improves RVEF, which persists during 36-month follow-up. This therapeutic strategy may enhance somatic growth and reduce incidence of heart failure.

DOI： 10.1016/j.jtcvs.2015.06.076

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Surgical outcome of hypoplastic left heart syndrome with intact atrial septum. International journal

Sadahiko Arai, Yasuhiro Fujii, Yasuhiro Kotani, Yosuke Kuroko, Shingo Kasahara, Shunji Sano

Asian cardiovascular & thoracic annals 23 ( 9 ) 1034 - 8 2015.11

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The surgical outcomes of hypoplastic left heart syndrome with intact atrial septum remains very poor in spite of the introduction of prenatal diagnosis before the Norwood operation. The hybrid operation consisting of bilateral pulmonary artery banding and balloon atrioseptectomy is one of the treatment strategies to potentially improve this patient population, however, the long-term outcomes are unknown. METHODS: Six consecutive patients with hypoplastic left heart syndrome with intact atrial septum, who underwent the hybrid operation between October 2006 and July 2014, were retrospectively reviewed. Hypoplastic left heart syndrome with highly restrictive atrial communication was excluded. RESULTS: Three patients died after the hybrid operation, due to sepsis, cerebral bleeding, and heart failure. Three patients underwent the modified Norwood operation. One of these died due to severe hypoxia while awaiting the bidirectional Glenn operation. The others underwent a bidirectional Glenn operation and subsequent Fontan completion but died due to lung dysfunction and sudden hemoptysis. CONCLUSIONS: The hybrid operation for hypoplastic left heart syndrome with intact atrial septum may have improved the neonatal outcome and Fontan completion rate in this extremely high-risk group of patients, but the long-term outcome remains dismal. Considering the late mortality related to pulmonary complications, aggressive fetal intervention to create a nonrestrictive atrial septal communication to promote normal development of the pulmonary vessels may be the last resort to improve the long-term outcome.

DOI： 10.1177/0218492315606581

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Left Ventricular Myxoma Occluding the Suprarenal Abdominal Aorta in an Infant. International journal

Takuya Kawabata, Shingo Kasahara, Shin-ichi Ohtsuki, Yosuke Kuroko, Yasuhiro Kotani, Yasuhiro Fujii, Ko Yoshizumi, Sadahiko Arai, Shunji Sano

The Annals of thoracic surgery 100 ( 1 ) 309 - 11 2015.7

Language：English Publishing type：Research paper (scientific journal)

Myxoma is the most common primary cardiac tumor in adults; however, it is extremely rare in infants. Acute occlusion of the abdominal aorta by a cardiac myxoma is also rare. We report the case of an infant with acute occlusion of the suprarenal abdominal aorta by a left ventricular myxoma. The patient underwent successful catheter embolectomy of the abdominal aorta and surgical resection of the cardiac myxoma. This is a very rare case report of the combination of infantile left ventricular myxoma and acute occlusion of the abdominal aorta.

DOI： 10.1016/j.athoracsur.2014.08.066

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Current Management of Severe CHF by Mechanical Support and Cardiac Transplant 左心低形成症候群に対する心筋幹細胞を用いた再生医療

佐野俊二, 樽井俊, 石神修大, 小林純子, 後藤拓弥, 奥山倫弘, 逢坂大樹, 黒子洋介, 馬場健児, 大月審一, 新井禎彦, 笠原真悟, 王英正

日本小児循環器学会雑誌 31 ( Suppl.1 ) s1 - 147 2015.7

Fontan循環不全の心停止患者に対してV-A Extracorporeal Membrane Oxygenationが奏功した1症例

高寛, 伊藤英史, 堂口琢磨, 氏家良人, 笠原真悟, 佐野俊二

体外循環技術 42 ( 2 ) 133 - 136 2015.6

Language：Japanese Publisher：(一社)日本体外循環技術医学会編集委員会

Fontan循環不全の心停止患者に対してV-A extracorporeal mambrane oxygenation(ECMO)が奏功した1症例を経験したので報告する。患者は40歳の男性で身長161cm、体重55.6kg、体表面積1.48m2であった。2013年4月からFontan循環不全による蛋白漏出性胃腸症および腹水貯留を認め、Biderectional Glenn(BDG)とmodified B-T shunt(m-BTS)手術へ移行する予定で同年5月に当院へ入院した。入院中に痙攣発作から心停止となりECMOを導入した。ECMOは右総頸動脈送血、左大腿静脈脱血にて行い灌流量は2.4L/min/m2で管理した。ECMO導入後は循環動態が安定し中心静脈圧は20mmHgから10mmHgへ減少した。ECMO導入後に神経障害、多臓器不全を認めなかった。Fontan循環不全の心停止患者に対してECMOを導入することによって静脈圧を下げることができ、安定した全身循環を保ちつつBDGとm-BTS手術へ移行することが可能であった。(著者抄録)

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頻脈誘発性心筋症による心原性ショックに対してExtracorporeal membrane oxygenationを導入し奏功した1症例

宮本綾子, 伊藤英史, 高寛, 西村まどか, 堂口琢磨, 氏家良人, 笠原真悟, 佐野俊二

体外循環技術 42 ( 2 ) 137 - 140 2015.6

Language：Japanese Publisher：(一社)日本体外循環技術医学会編集委員会

頻脈誘発性心筋症(tachycardia induced cardiomyopathy:TIC)による心原性ショックに対してExtracorporeal membrane oxygenation(ECMO)を導入し奏功した1症例を経験したので報告する。患者は2歳10ヵ月の女児で身長84.5cm、体重10kgであった。生後1ヵ月に多発性筋性部心室中隔欠損症、多源性心房頻拍と診断され、生後2ヵ月で肺動脈絞扼術を施行した。2012年10月に心拍数190回/分、収縮期血圧50mmHg、拡張期血圧35mmHg、平均血圧40mmHg、心臓超音波検査で左室駆出率(left ventricular ejection fraction:LVEF)が13%、無尿で心原性ショック状態であり抗不整脈薬を投与しても改善が認められないためECMOを導入した。ECMO導入後も抗不整脈薬の投与を継続した。ECMO導入後に心拍数、左室拡張末期径と血清脳性ナトリウム利尿ペプチドの減少、更にLVEFの改善を認めたことからTICと診断した。ECMOにより循環動態を保ちながら、抗不整脈薬の投与を継続したことで心拍数の正常化を得ることができ、心機能の改善を認めたと考える。(著者抄録)

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Acute respiratory distress syndrome in a child with severe epileptic disorder treated successfully by extracorporeal membrane oxygenation: a case report. International journal

Nobuyuki Nosaka, Shingo Ichiba, Kohei Tsukahara, Emily Knaup, Kumiko Hayashi, Shingo Kasahara, Yoshinori Kobayashi, Makio Oka, Katsuhiro Kobayashi, Harumi Yoshinaga, Yoshihito Ujike

BMC pediatrics 15 29 - 29 2015.4

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is now a candidate therapy for children with acute respiratory failure. CASE PRESENTATION: We report our experience of using central ECMO therapy for acute respiratory distress syndrome followed by seizure in a 15-month-old girl with a severe epileptic disorder. Her respiratory distress was refractory to standard medical treatment and mechanical ventilatory support. Her condition was complicated by development of a pneumothorax. The patient was successfully weaned off ECMO and discharged without deterioration of her neurological status. CONCLUSION: The successful outcome in this case resulted from the central ECMO, which enabled "lung rest" and adequate cerebral blood flow. In skilled ECMO facilities, early implementation of ECMO would give some advantages to patients such as the one presented here. Given the invasiveness and the ease of the procedure, introduction of dual-lumen catheters adequately sized for pediatric patients in Japan is required.

DOI： 10.1186/s12887-015-0348-1

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小児心不全に対する心臓内自己幹細胞移植療法による右室リモデリング退縮効果の解明

石神修大, 後藤拓弥, 奥山倫弘, 逢坂大樹, 新井禎彦, 笠原真悟, 佐野俊二, 王英正

日本外科学会定期学術集会抄録集 115回 CR - 2 2015.4

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Papers - KASAHARA Shingo