Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Hazumu Nagata Last modified date:2021.05.28

Assistant Professor / Department of Perinatal and Pediatric Medicine, Gratuated School of Medical Sciences, Kyushu University / Pediatrics / Kyushu University Hospital

1. Kiyoshi Uike, Hazumu Nagata, Yuichiro Hirata, Kenichiro Yamamura, Eiko Terashi, Toshiharu Matsuura, Eiji Morihana, Kazuhiro Okubo, Kanako Ishii, Yasunari Sakai, Tomoaki Taguchi, Shoichi Ohga, Effective shunt closure for pulmonary hypertension and liver dysfunction in congenital portosystemic venous shunt, Pediatric Pulmonology, 10.1002/ppul.23944, 53, 4, 505-511, 2018.04, Objective: Congenital portosystemic venous shunt (CPSVS) is a rare vascular malformation with a high risk of mortality from pulmonary arterial hypertension (PAH), but the treatment outcome of CPSVS closure remains elusive. Our aim was to investigate the clinical features and establish the optimal management of CPSVS with or without PAH. Methods: Twenty-four patients with CPSVS treated in Kyushu University Hospital between 1990 and 2015 were enrolled in this study. The patients were divided into a PAH group (n = 9) and a non-PAH group (n = 15). Clinical characteristics and outcomes were evaluated. Results: The first manifestation of CPSVS at diagnosis (28.5 [1-216] months) was hypergalactosemia in 13 (54%) or PAH in six (25%) patients. PAH was the cause of all three deaths. The PAH group had higher levels of serum total bile acid, manganese, and total bilirubin, along with higher pulmonary vascular resistance index (PVRI) than the non-PAH group (7.2 [5.1-38.1] vs 1.2 [0.5-3.3] unit/m 2 , P < 0.001). Five of nine PAH patients underwent CPSVS closure at a median of 38 months (range 21-118) after PAH diagnosis. Pulmonary artery pressure improved after CPSVS closure with PAH-specific therapy, but normal range was not achieved. CPSVS closure improved the hepatic synthetic function of four PAH patients. Eigh­t of 15 non-PAH patients who received CPSVS closure did not develop PAH for a median of 34.5 months (range 6-164) after the procedure. Conclusions: CPSVS closure with PAH-specific therapy successfully controlled PAH. Early CPSVS closure may prevent the occurrence and progression of PAH with CPSVS.­..
2. Koichiro Yoshimaru, Toshiharu Matsuura, Yoshiaki Takahashi, Yusuke Yanagi, Hazumu Nagata, Shoichi Ohga, Tomoaki Taguchi, The efficacy of serum brain natriuretic peptide for the early detection of portopulmonary hypertension in biliary atresia patients before liver transplantation, Pediatric Transplantation, 10.1111/petr.13203, 22, 5, 2018.08, Severe portopulmonary hypertension (POPH) is a contraindication for liver transplantation (LT) because of the high risk of postoperative heart failure. The early detection of POPH is important for patients with biliary atresia (BA). Brain natriuretic peptide (BNP) is known to be correlated with liver fibrosis in patients with liver cirrhosis. The aim of this study was to elucidate the efficacy of BNP measurement for the follow-up of patients with BA. Thirty-two patients with BA were identified from September 2011 to December 2016. As indices of liver fibrosis/cirrhosis, APRI (P <.0001), FIB-4 (P <.0001), Child-Pugh score (P <.0001), IV collagen (P =.0005), and hyaluronic acid (P =.0291) had high or moderate correlations with BNP. Patients with splenomegaly, esophageal varices, liver fibrosis, and collateral veins had significantly higher BNP levels than those without. Patients diagnosed with POPH had significantly higher BNP levels in comparison with those patients without (P =.0068). In contrast, PELD/MELD scores showed an almost negligible correlation with the BNP level. LT was successful in 3 asymptomatic BA patients with POPH who had high BNP levels despite the low PELD/MELD scores. In conclusion, routine serum BNP surveillance can be easy to predict asymptomatic POPH. This may help to identify POPH before it reaches a stage that would contraindicate LT..
3. Yuzo Yamasaki, Satoshi Kawanami, Takeshi Kamitani, Koji Sagiyama, Seitaro Shin, Takuya Hino, Hazumu Nagata, Hidetake Yabuuchi, Michinobu Nagao, Hiroshi Honda, Patient-related factors influencing detectability of coronary arteries in 320-row CT angiography in infants with complex congenital heart disease, International Journal of Cardiovascular Imaging, 10.1007/s10554-018-1363-8, 34, 9, 1485-1491, 2018.09, To investigate the performance of second-generation 320-row computed tomographic (CT) angiography (CTA) in detecting coronary arteries and identify factors influencing visibility of the coronary arteries in infants with complex congenital heart disease (CHD). Data of 60 infants (aged 0–2 years, median 2 months) with complex CHD who underwent examination using 320-row CTA with low-dose prospective electrocardiogram-triggered volume target scanning were reviewed. The coronary arteries of each infant were assessed using a 0–4-point scoring system based on the number of coronary segments with a visible course. Clinical parameters, the CT value in the ascending aorta, image noise, and the radiation dose were subjected to univariate and multivariate analyses. The mean coronary score for all examinations was 2.6 ± 1.5 points. The mean attenuation in the ascending aorta was 306.7 ± 66.2 HU and the mean standard deviation was 21.7 ± 4.4. The mean effective radiation dose was 1.27 ± 0.39 mSv. Multivariate regression analysis showed significant correlations between coronary score and body weight (p < 0.05) and between coronary score and the CT value in the ascending aorta (p < 0.02). Second-generation 320-row CTA with prospective electrocardiogram-triggered volume target scanning and hybrid iterative reconstruction allows good visibility of the coronary arteries in infants with complex CHD. Body weight and the CT value in the ascending aorta are important factors influencing the visibility of the coronary arteries in infants..
4. Yusaku Nagatomo, Jun Muneuchi, Yasutaka Nakashima, Etsuro Nanishi, Hiromitsu Shirozu, Mamie Watanabe, Kiyoshi Uike, Hazumu Nagata, Yuichiro Hirata, Kenichiro Yamamura, Yasuhiko Takahashi, Seigo Okada, Yasuo Suzuki, Shunji Hasegawa, Shoichi Ohga, Effective infliximab therapy for the early regression of coronary artery aneurysm in Kawasaki disease, International Journal of Cardiology, 10.1016/j.ijcard.2018.04.062, 271, 317-321, 2018.11, Background: There is limited information available regarding the role of infliximab (IFX) following the acute phase of Kawasaki disease (KD). We aimed to evaluate whether IFX is associated with coronary artery aneurysm (CAA) regression. Methods: Between 2005 and 2016, we identified 971 consecutive patients with KD from 3 tertiary institutions, and 49 (5%) with CAAs were enrolled in our study. Patients were divided into 2 groups: 27 who received IFX and 22 who did not. The persistence rate of CAAs was compared between the groups. Results: Age, sex, and duration of the febrile period did not significantly differ between the groups. The maximum value of C-reactive protein was higher in the IFX- than in the non-IFX group. The maximum z-score of CAAs did not differ between the groups. The 2-, 4- and 6-year cumulative persistence rate of CAA was 24%, 24% and 24% in IFX-group, whereas 67%, 52% and 33% in non-IFX group, respectively (P = 0.03). The median duration of CAA regression was 1.1 vs. 4.6 years. Among those who developed medium- or large-sized CAAs, the 2-, 4- and 6-year cumulative persistence rate of CAA was 33%, 33% and 33% in IFX group, whereas 77%, 51% and 48% in non-IFX group, respectively (P = 0.047). Multivariate logistic regression analysis indicated that the maximum z-score (hazard ratio 0.72, p < 0.001) and response to IFX (hazard ratio 4.56, p = 0.017) were independently related to regression. Conclusion: IFX therapy was observed to be effective for the early improvement of CAAs in patients with intravenous immunoglobulin-resistant KD..
5. Yuka Matsunaga, masataka ishimura, Hazumu Nagata, Kiyoshi Uike, Tadamune Kinjo, Masayuki Ochiai, Kenichiro Yamamura, Hidetoshi Takada, Yoshihisa Tanoue, Masaki Hayakawa, Masanori Matsumoto, Toshiro Hara, Shoichi Ohga, Thrombotic microangiopathy in a very young infant with mitral valvuloplasty, Pediatrics and Neonatology, 10.1016/j.pedneo.2018.02.002, 59, 6, 595-599, 2018.12, Background: Thrombotic microangiopathies (TMA) are microvascular occlusive disorders characterized by systemic or intrarenal platelet aggregation, thrombocytopenia, and red cell fragmentation. Post-operative TMA mostly occurs in adult patients with cardiovascular surgery, with the distinct pathophysiology from classical thrombotic thrombocytopenic purpura (TTP) although the exact pathophysiology remains unclear. Case presentation: A one-month-old infant developed TMA after the initial surgery of double outlet right ventricle. ADAM metallopeptidase with thrombospondin type 1 motif 13 (ADAMTS13) activity was sustained (64%) with the undetectable inhibitor. Von Willebrand factor (VWF) multimer analyses showed absent high-molecular weight multimers. Echocardiography disclosed severe mitral regurgitation. The mitral valve repair 32 days after the initial valvuloplasty led to prompt resolution of TMA. These suggested that TMA occurred in association with valvulopathy-triggered turbulent shear flow, mechanical hemolysis and endothelial damage. The consumption of large VWF multimers might account for the vascular high shear stress shown in Heyde syndrome. Conclusion: The youngest case of post-operative TMA underscores the critical coagulopathy after the first surgical intervention for congenital heart disease..
6. Hazumu Nagata, Eiko Terashi, Mamoru Muraoka, Kiyoshi Uike, Yuichiro Hirata, Hideki Tatewaki, Yasuyuki Fujita, Kenichiro Yamamura, Shoichi Ohga, High incidence of ductal closure or narrowing at birth in patients with right ventricular outflow tract obstruction with normal orientation of the ductus arteriosus, Cardiology in the Young, 10.1017/S1047951118001798, 29, 1, 54-58, 2019.01, Background Ductal patency is mandatory to manage patients with ductal-dependent pulmonary circulation. The aim of this study is to elucidate the morphological and haemodynamic features of ductus arteriosus with right ventricular outflow tract obstruction, and investigate the appropriate perinatal management.Patients and methods Patients with prenatal diagnosis of right ventricular outflow tract obstruction at our institution between 2010 and 2015 were included in the study. Reverse orientation of the ductus arteriosus is defined as an inferior angle of 90° at the aortic junction, and normal orientation of the ductus arteriosus as an angle of >90°. We retrospectively reviewed the shape and flow pattern of ductus arteriosus and the clinical characteristics of the cases.Results A total of 39 patients were enrolled. The shape was divided into normal orientation (n=15) and reverse orientation (n=24) of the ductus arteriosus. There was no significant difference in the type of oxygen saturation at birth and age at shunt operation between both the groups. However, the median narrowest diameter of ductus arteriosus in the normal orientation group was significantly smaller than that in the reverse orientation group (2.0 [1.0-5.4] versus 3.0 [1.3-4.4] mm, p0.05). In two patients of the normal orientation group, ductus arteriosus had closed at birth, and one of whom died because of severe cyanosis.Conclusions Normal orientation pattern might have high incidence of an early narrowing or closure of ductus arteriosus at birth. The critical patients need careful evaluation by repeated foetal echocardiography and further maternal interventions..
7. Yasutaka Nakashima, Etsuro Nanishi, Kenichiro Yamamura, Kiyoshi Uike, Eiko Terashi, Yuichiro Hirata, Hazumu Nagata, Eiji Morihana, Tamami Tanaka, Satoshi Honjo, Hidetoshi Takada, Shoichi Ohga, Procalcitonin levels predicting the infliximab response of immunoglobulin resistant Kawasaki disease, Cytokine, 10.1016/j.cyto.2018.11.025, 114, 26-31, 2019.02, Objective: To search the predictive factors of infliximab resistance in intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) patients. Study design. Twenty-seven patients with KD who received infliximab after 4–5 g/kg of IVIG therapy from 2013 to 2015 were consecutively recruited in this study. They were divided into two groups: patients who responded to infliximab (infliximab-responsive group, n = 15) and patients who required additional therapy for the disease control (infliximab-resistant group, n = 12). We analyzed the clinical and laboratory parameters just before the infliximab treatment including serum levels of procalcitonin and cytokines with respect to the infliximab response. Results: Serum procalcitonin concentration (P = 0.017), neutrophils to lymphocytes ratio (P = 0.013), and % neutrophils (P = 0.004) were higher, and serum sodium concentration (P = 0.017) was lower in infliximab-resistant group than those of infliximab-responsive group, respectively. Multivariate logistic regression analyses indicated that higher procalcitonin concentration (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.00–5.00, P = 0.046) and lower sodium levels (OR 0.64, 95% CI 0.32–1.00, P = 0.047), but not other variables, were associated with infliximab-resistance. Serum procalcitonin concentrations positively correlated with the serum levels of interleukin-6, soluble tumor necrosis factor receptor type 1 and type 2, respectively. Analyses of the receiver operating characteristic (ROC) curve showed that the cut-off value of procalcitonin 2.0 ng/ml had 58.3% of sensitivity and 93.3% of specificity. ROC analysis yielded an area under the curve (AUC) of 0.739 to predict infliximab-resistance. Conclusion: Serum procalcitonin might be an effective biomarker to predict infliximab resistance in severe KD patients who are refractory to IVIG treatment..
8. Kenichiro Yamamura, Ichiro Sakamoto, Eiji Morihana, Yuichiro Hirata, Hazumu Nagata, Yuzo Yamasaki, Yukihiko Okumura, Kenichi Kouhashi, Kazuhiro Koto, Hiroyuki Tsutsui, Shoichi Ohga, Elevated non-invasive liver fibrosis markers and risk of liver carcinoma in adult patients after repair of tetralogy of Fallot, International Journal of Cardiology, 10.1016/j.ijcard.2019.04.032, 287, 121-126, 2019.07, Background: Congestive hepatopathy and hepatocellular carcinoma is a serious complication after Fontan procedure. Liver fibrosis due to hepatic congestion could occur also in adult patients after repair of tetralogy of Fallot (rTOF). However, the incidence and severity remain unclear. Methods: A total of 111 patients with adult congenital heart disease between 2009 and 2016 were enrolled. Liver fibrosis markers and hemodynamic parameters assessed by cardiac magnetic resonance imaging and catheterization were analyzed in 50 rTOF patients having significant pulmonary regurgitation and/or stenosis, 50 Fontan patients and 11 controls. Results: Liver fibrosis markers in patients with rTOF were significantly higher than controls, and tended to be lower than Fontan patients (median, hyaluronic acid: 25.8 vs. 15.9 vs. 40.8, type IV collagen: 129 vs. 113 vs. 166, ng/mL, p < 0.05, respectively). Patients with rTOF showed abnormal hyaluronic acid levels more frequently than controls, and less frequently than Fontan patients (22% vs. 0% vs. 38%, respectively, p < 0.05). Multivariate analyses indicated a positive association of right atrial pressure with type IV-collagen or hyaluronic acid levels (each, p < 0.001, p = 0.003). Abdominal ultrasonography revealed hepatic congestion in 50% of rTOF patients tested. Liver biopsy of the two rTOF patients with highest hyaluronic acid levels showed pathological evidence of moderate and severe (F2 and F3)liver fibrosis and one had combined hepatocellular and cholangiocarcinoma. Conclusions: We first demonstrated elevated liver fibrosis markers in adult patients with rTOF. These levels may help to predict the progressive liver disease as well as consider the timing of pulmonary valve replacement..