Makoto Nakazawa

Toho University, Edo, Tōkyō, Japan

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Publications (130)384.15 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Myocarditis (MC) is an important cause of cardiac dysfunction in children. Fulminant MC is sometimes fatal, and sequelae may develop during follow-up. We conducted a nationwide survey to determine the clinico-epidemiological features of MC in Japanese children and adolescents. Survey questionnaires were mailed to 627 hospitals, which were asked if they had treated MC patients aged between 1 month and 17 years during the period from January 1997 through December 2002. Responses were collected until December 2005, and data were collected and analyzed until January 2008. A total of 169 patients were reported: 64 fulminant cases, 89 acute cases, and 8 chronic cases. Incidence was 43.5 cases/year and 0.26 cases/100,000. Pathogens were identified in 37 patients; coxsackie virus accounted for 60%. Major cardiovascular manifestations at onset were congestive heart failure, refractory arrhythmia, and syncope in 70, 37, and 17 patients, respectively. Intravenous immunoglobulin was administered to 73 patients. Mechanical support seemed to be effective and life-saving. Among the 169 patients, 123 survived. Cardiovascular sequelae were reported in 49 patients. The survival rate for children with fulminant MC was disappointing. Overall, two-thirds of survivors had no sequelae. Mechanical support may reduce the mortality and the risk of clinical worsening.
    Circulation Journal 02/2012; 76(5):1222-8. · 3.58 Impact Factor
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    ABSTRACT: BACKGROUND: There are few articles on mortality and morbidity of adult patients with Eisenmenger's syndrome (ES) in the current era when disease targeting therapy (DTT) has been available. METHODS AND RESULTS: 198 patients (a median age 35years, 64% female) with ES who visited the 16 participating institutes in Japan and Korea from 1998 to 2009 were enrolled. Clinical data during adulthood were collected from each institutional chart and analyzed centrally. During a median follow-up of 8years, 30 patients died including 14 sudden deaths. 89 patients took oral medication of DTT and clinical improvement was observed in 54 of them. However, survival rate in patients taking DTT was not different from those without (87% vs 84%, p=0.55). When the clinical data in between first and last clinic visits were compared in 85 patients, the patients with NYHA ≧ III increased from 24% to 48% (p<0.001), SpO(2) decreased from 89% to 85% (p=0.008) and hematocrit increased from 51.4% to 52.9% (p=0.04). Non-survivors had poorer NYHA function class, lower body weight (BW), lower body mass index (BMI), and higher serum level of Cr at the first visits than survivors. CONCLUSIONS: Long term survival and clinical status of adult patients with ES remains unsatisfactory even in the current era of DTT. Poor NYHA functional class, low BW, low BMI and high serum level of Cr were related to mortality. DTT therapy improved clinical status in many patients with Eisenmenger's syndrome, but no significant impact on survival could be shown.
    International journal of cardiology 01/2012; · 6.18 Impact Factor
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    ABSTRACT: Despite the recent progress of cardiac surgery, the indications for surgical intervention during the active phase of infective endocarditis have not yet been established in patients with congenital heart diseases due to the limited number of such patients. The present study aims to determine the surgical indications for active infective endocarditis in congenital heart diseases. A retrospective observational cohort multi-center study on infective endocarditis with congenital heart diseases was conducted from January 1997 to December 2001 in Japan and 239 patients were registered. Sixty-one (26%) of the 239 patients had undergone surgical therapy for active infective endocarditis, which was defined as cardiac surgery during administration of intravenous antibiotics. There were 7 deaths (11%). A univariate regression analysis revealed that the factors significantly associated with the need for surgical intervention for active IE were the lack of diagnosis of cardiac disorders before the onset of infective endocarditis, aortic valve infective endocarditis, perivalvular abscess, presence of heart failure, and change of antibiotics. A stepwise logistic regression analysis revealed that the presence of a perivalvular abscess, heart failure and a change in the antibiotics were independent determinant factors for the need for surgical treatment of active infective endocarditis in patients with congenital heart diseases. Surgery should therefore be considered even during the active phase in patients with congenital heart diseases and infective endocarditis, when they develop associated with heart failure, a perivalvular abscess, or the need for a change in antibiotics.
    International journal of cardiology 12/2010; 157(1):59-62. · 6.18 Impact Factor
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    Yoshiki Mori, Makoto Nakazawa, Toshikatsu Yagihara
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    ABSTRACT: Pediatric cardiac catheterization is sometimes associated with serious complications. However, there are no data regarding the organization of pediatric cardiac catheterization laboratories to minimize complications. The aim of this study was to determine the current organization of pediatric cardiac catheterization laboratories with regard to patient safety in Japan. We sent questionnaires to 105 institutions and obtained data from 82. Major complications requiring surgical therapy or death occurred in 22 institutes (27%). The incidence of major complications did not relate to the number of procedures performed. The procedures were performed without written informed consent in 21% of all institutions. The time to inform about the procedures was within 30 min in 43 institutes (52%). A pre-procedure meeting was held in 56 institutions (68%). The anesthetist attended the diagnostic procedures in 23% and the therapeutic procedures in 53%. The drugs and defibrillator for resuscitation were available in almost all institutions, but a pacemaker was not in 23 institutions (28%). The procedures were performed under the "back-up" of cardiovascular surgeons in 38 institutions (46%). There are still large numbers of institutions in Japan, which need much improvement in the organization of pediatric cardiac catheterization laboratories as an aspect of patient safety.
    Journal of Cardiology 09/2010; 56(2):183-8. · 2.30 Impact Factor
  • Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2010; 55(10).
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    ABSTRACT: Congenital atresia of the left main coronary ostium is a rare coronary artery anomaly. A 3-year-old boy who was asymptomatic had a heart murmur because of mitral regurgitation. He underwent reconstruction of the left main coronary artery, but stenosis occurred in the early postoperative period. Although the patient underwent repair of the coronary artery stenosis, the distal portion of the left coronary artery re-stenosed. Percutaneous transluminal coronary angioplasty for the stenosis was performed successfully and there has not been any sign of re-stenosis for 30 months to date.
    Circulation Journal 07/2009; 73(12):2360-2. · 3.58 Impact Factor
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    ABSTRACT: Thromboembolic events account for significant morbidity and mortality after the Fontan procedure, but the underlying mechanisms remain unclear. P-selectin on platelets indicates platelet activation. Thrombomodulin (TM), a receptor for thrombin and a major anticoagulant proteoglycan on the endothelial membrane, reflects the anticoagulant activity of the endothelium. The present study investigated the hypothesis that the balance between platelet activation and endothelial biological function is impaired in Fontan patients. Platelet P-selectin as a marker of platelet activation, plasma TM levels and protein C activity, as markers of anticoagulant activity of the endothelium, and thrombin-antithrombin complex III (TAT) were examined in 43 Fontan patients. P-selectin levels on platelets (4.5 +/-1.4 vs 3.4 +/-0.4 mean fluorescence intensity, P<0.001) and TAT levels (80.2 +/-322.6 vs 1.9 +/-0.9 ng/ml, P<0.05) were significantly higher in Fontan patients than in control subjects. On the other hand, plasma TM levels (1.5 +/-0.8 vs 2.2 +/-0.3 FU/ml, P<0.01) and protein C activity (71 +/-35 vs 118 +/-25%, P<0.001) were significantly lower in Fontan patients compared with controls. These abnormalities were not seen in patients after other surgical procedures for congenital heart disease. Platelet activation is enhanced and endothelial function is impaired in patients after the Fontan procedure, which may partly explain the thromboembolic complications in Fontan patients.
    Circulation Journal 07/2009; 73(9):1705-10. · 3.58 Impact Factor
  • Tsutomu Saji, Makoto Nakazawa, Kensuke Harada
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    ABSTRACT: A questionnaire study was performed to determine the current status of palivizumab prophylaxis against respiratory syncytial virus infection in Japanese children with congenital heart disease <2 years of age. Palivizumab prophylaxis decreased the respiratory syncytial virus hospitalization rate by 42.8%.
    The Pediatric Infectious Disease Journal 10/2008; 27(12):1108-9. · 3.57 Impact Factor
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    ABSTRACT: After the arterial switch procedure, decreased distensibility of the aortic root has been reported, which means impaired aortic reservoir function of the coronary circulation, but there have been no reports regarding the relationship of this issue to myocardial perfusion. Therefore, in the present study the aortic reservoir function and coronary supply-demand balance were examined in patients after undergoing the arterial switch operation (ASO) around the time of entering elementary school. Diastolic runoff (DR), which is the percentage of diastolic blood flow to total cardiac output, was measured as the index of aortic reservoir function. The subendocardial viability ratio was investigated as the index of coronary supply - demand balance. In the patient group, the aortic root was dilated (p<0.0001) and distensibility was impaired (p<0.0001) in comparison with an age-matched control group. However, there was no difference between the 2 groups in DR or subendocardial viability ratio. Coronary supply - demand balance was preserved in the pediatric ASO patients, despite the aortic root dysfunction. The preserved DR suggests that dilatation of the aorta compensates for aortic reservoir function. Because large artery dysfunction predicts future cardiovascular diseases, careful follow-up is crucial.
    Circulation Journal 08/2008; 72(8):1291-5. · 3.58 Impact Factor
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    ABSTRACT: Mutations of the bone morphogenetic protein receptor II gene (BMPR2), and 1 mutation of the activin receptor-like kinase 1 gene (ALK1) have been reported in patients with pulmonary arterial hypertension (PAH). A genomic study of ALK1 and BMPR2 was conducted in 21 PAH probands under 16 years of age to study the relationship between the clinical features of the patients and these genes. In all 4 familial aggregates of PAH, 3 ALK1 or 1 BMPR2 mutations were identified. Among 17 probands aged between 4 and 14 years with idiopathic PAH, 2 ALK1 mutations (2/17: 11.8%) and 3 BMPR2 mutations (3/17: 17.6%; 5 mutations in total: 5/17: 29.4%) were found. Each proband with the ALK1 mutation developed PAH, as did the probands with the BMPR2 mutation. Hence, it is proposed that ALK1 plays as notable a role as BMPR2 in the etiology of PAH. Furthermore, asymptomatic carriers with the ALK1 mutation within the serine - threonine kinase domain are at risk of developing PAH and hereditary hemorrhagic telangiectasia, so close follow-up is recommended for those individuals.
    Circulation Journal 02/2008; 72(1):127-33. · 3.58 Impact Factor
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    ABSTRACT: Despite developments in preventative and medical therapy, infective endocarditis (IE) carries a high rate of mortality. Risk factors for mortality are unknown in pediatric and adult patients with congenital heart disease (CHD). We determined the risk factors for in-hospital mortality in pediatric and adult patients with CHD. A retrospective observational cohort study was conducted from January 1997 to December 2001 in Japan. Of the 239 patients for whom complete data were available, 216 patients with CHD were identified. Outcomes were alive or deceased. The proposed modified Duke's criteria identified 137 patients, aged 1 month to 62 years with a median of 12 years, with IE. In-hospital mortality was 10%. Four risk factors were independently associated with mortality by stepwise logistic regression analysis: (1) vegetation size > or =20 mm (odds ratio 40.6, 95% confidence interval 2.42 to 681); (2) age <1 year (odds ratio 19.5, 95% confidence interval 1.74 to 219); (3) presence of heart failure (odds ratio 7.16, 95% confidence ratio 1.34 to 38.4); and (4) Staphylococcus aureus as a causative organism (odds ratio 5.68, 95% confidence interval 1.16 to 27.9). Surgical intervention emerged as a predictive factor for lower in-hospital mortality (odds ratio 0.045, 95% confidence interval 0.003 to 0.70) by stepwise logistic regression analysis. In conclusion, surgical intervention, which decreases the risk of in-hospital mortality, should always be considered.
    The American Journal of Cardiology 02/2008; 101(1):114-8. · 3.21 Impact Factor
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    ABSTRACT: Infective endocarditis (IE) due to Streptococcus pneumoniae (S. pneumoniae) carries a high mortality rate. However, little is known about pneumococcal IE in children and no optimal therapy has been established. Thus, we attempted to identify the clinical features of this disorder through a Japanese nationwide survey. Members of the Japanese Society of Pediatrics Cardiology and Cardiac Surgery registered 170 pediatric patients with IE diagnosed during a 5-year period (1997-2001). Nine of these patients (5.3%) had pneumococcal IE. The clinical course, treatment and outcome of these 9 patients, aged 7 months to 4 years, were analyzed. Pneumococcal IE was associated with congenital heart disease in 7 patients and accompanied by other systemic infections including meningitis, pneumonia and otitis media, in 4 patients. Five of the 9 (55.6%) strains isolated by blood culture were penicillin-resistant S. pneumoniae strains. Seven patients were treated with carbapenem. Three underwent cardiac surgery due to cardiac failure and/or vegetation. One died due to septic shock on the first day of hospitalization. In children, pneumococcal endocarditis is often accompanied by severe systemic infections. The majority of pediatric cases are caused by penicillin-resistant S. pneumoniae strains. Carbapenem is an effective for IE caused by penicillin-resistant S. pneumoniae. This survey might be helpful to establish proper management strategies for pediatric pneumococcal IE.
    International journal of cardiology 02/2008; 123(3):298-301. · 6.18 Impact Factor
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    ABSTRACT: Tachyarrhythmia during pregnancy may have an adverse effect on the mother and the fetus. Heart rate variability (HRV) is a significant marker of autonomic nervous function and may predict tachyarrhythmia. HRV and incidence of arrhythmia in women with repaired congenital heart disease (CHD) during pregnancy were examined. Twenty-eight patients with repaired CHD (35 pregnancies, age: 26+/-3.5 years at their first pregnancy, 22+/-6.2 years post-repair) and 19 healthy pregnant volunteers (controls, 19 pregnancies, age: 28+/-5.5 years) were enrolled. Holter monitoring and laboratory tests were examined at 28+/-4 weeks of gestation and 22+/-13 weeks postpartum in patients and 28+/-3 weeks of gestation in controls. Time and frequency variables of HRV were analyzed. Compared with controls and postpartum, there was a significantly higher incidence of tachyarrhythmia during pregnancy in women with CHD (4 episodes of supraventricular tachyarrhythmia (SVT) and 5 of non-sustained ventricular tachycardia, P=0.02). HR response in tetralogy of Fallot was impaired (781+/-50 ms, P=0.02). Most of HRV variables were significantly suppressed (average RR 740+/-64 ms, SDRR 99+/-22 ms, low and high frequency domains (341+/-165 ms2 and 256+/-181 ms2) (P<0.05). Reduced SDRR and high frequency domains were observed in patients with tachyarrhythmia. Furthermore, there were increased left ventricular end-diastolic dimensions 48+/-5 mm (P=0.001) and atrial natriuretic peptide levels 33+/-13 pg/ml (P=0.01) in the CHD patients compared with postpartum levels. Impaired autonomic nervous activity, volume overload of the heart and operative scar all play a contributory role in higher incidence of tachyarrhythmia during pregnancy in patients with repaired CHD compared to healthy pregnant controls. Close monitoring of patients with CHD for tachyarrhythmia during pregnancy is, thus, warranted.
    International journal of cardiology 12/2007; 122(2):143-8. · 6.18 Impact Factor
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    11/2007: pages 273 - 276; , ISBN: 9780470988664
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    11/2007: pages 282 - 284; , ISBN: 9780470988664
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    ABSTRACT: Although not all newborns with Ebstein's anomaly present with severe cardiomegaly in utero, some of them cannot live after birth because of the lung hypoplasia. To clarify the relationship between the intrauterine cardiomegaly and the outcome of the patients with Ebstein's anomaly or tricuspid valve dysplasia, we calculated the ratio of the area of the heart against the thorax (CTAR) in the transverse view of the thorax at the level of the cardiac four-chamber view in the fetal echocardiogram and compared it to the outcome. The study population consisted of four patients with Ebstein's anomaly and one patient with tricuspid valve dysplasia who were diagnosed in utero. The ranges obtained from 53 normal fetal cases were 20%± 8% (mean ± 2 SD) at below 20 week's gestation, 25%± 10% at the gestational age of 21 to 30 weeks, and 29%± 6.4% at the gestational age of 31 to 40 weeks. The CTARs of these five cases measured 81.6%, 51%, 55.2%, 47.5%, and 75.6%, respectively, and were abnormally higher than the normal value. Two fetuses died in utero with severe hydrops fetalis. Two fetuses whose cardiothoracic ratios by chest X ray were 100% died at twelve hours of life. One patient died at 110 days. The cross-sectional area of the thorax was smaller than the normal range in 3 (cases 1, 4, and 5) out of these 5 cases. Thus, we conclude that fetal Ebstein's anomaly and tricuspid valve dysplasia associated with massive tricuspid regurgitation with a large CTAR ratio (higher than 50%) and small thoracic cross-sectional area has a very poor prognosis bothprena-tally and neonatally. (ECHOCARDIOGRAPHY, Volume 11, May 1994)
    Echocardiography 08/2007; 11(3):215 - 220. · 1.26 Impact Factor
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    ABSTRACT: Adults with cyanotic congenital heart disease (CCHD) are associated with a significant incidence of morbid events and premature deaths that may be predicted during childhood. We aimed to identify predictive factors related to long-term prognosis through a Japanese multi-center cross-sectional study. Data were collected from 253 adults with CCHD (126 men; age 28 (18 to 56) years) from 15 participating centers between 1998 and 2003. Laboratory data such as cardiothoracic ratio (CTR), percutaneous oxygen saturation (SpO2), hematocrit levels (Ht) and platelet counts (Pl-c) at the age of 15 years were collected for predictive factor analysis for death and cardiovascular and systematic events. Predictive factors were determined by multivariate Cox regression analysis. After a mean follow-up of 21 (0-42) years, 23 patients died with a median age of 29 (18-54) years (heart failure in 8, sudden in 6 and systematic complications in 9). Survival since 18 years of age was 91% and 84% at 10 and 20 years, respectively. Significant predictive factor for death was Pl-c<130x10(9)/l and for renal failure (n=7) was Ht>65%. 162 patients were hospitalized and predictors for hospitalization due to heart failure (n=45) were common atrioventricular canal CTR>60% and Pl-c<100x10(9)/l and that due to arrhythmias (n=44) were systematic right ventricle and CTR>60%. This multi-center study provides an objective basis of assessing the long-term prognosis in patients with CCHD. These data are useful in making decisions regarding medical management and in favorably altering the non-operative course of the disease.
    International journal of cardiology 08/2007; 120(1):72-8. · 6.18 Impact Factor
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    ABSTRACT: The basic mechanisms of thromboembolism in cyanotic congenital heart disease (CCHD) have not been well clarified. P-selectin on the platelets reflects platelet activation. Thrombomodulin is a critical cofactor for thrombin-mediated activation of protein C and reflects the anticoagulant activity of the endothelium. The present study was performed to evaluate whether platelet activation exists in patients with CCHD. Platelet P-selectin as a marker of platelet activation, plasma thrombomodulin level and protein C activity as markers of anticoagulant activity of the endothelium and thrombin - antithrombin complex III (TAT) were examined in 35 patients with CCHD. Plasma thrombomodulin level (1.1+/-0.9 vs 2.2+/-0.3 FU/ml) and protein C activity (71.1+/-29.8 vs 117.8+/-24.8%) were significantly lower in patients with CCHD as compared with the control subjects. The levels of plasma TAT (255+/-811 vs 1.9+/-0.9 ng/ml) and P-selectin on platelets (6.3 +/-4.5 vs 3.3+/-0.3 mean fluorescence intensity) were significantly higher in the patients with CCHD than in the controls. Four of the CCHD patients who experienced thromboembolic events had elevated levels of platelet P-selectin (p=0.02) compared with CCHD patients without thromboembolic events. Platelet activation exists in patients with CCHD and it may play an important role in the thromboembolic events in CCHD.
    Circulation Journal 07/2007; 71(6):948-53. · 3.58 Impact Factor
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    ABSTRACT: Aortopulmonary collaterals (APCs) are frequently observed before and after the Fontan procedure. However, the mechanism of the development of APCs is unknown. We hypothesized that one or several antiangiogenic and/or angiogenic growth factors might play a role in the development of APCs. Eighty-five patients were enrolled and divided into 3 groups (Fontan group: 30 patients after the Fontan procedure, cyanotic group: 29 patients with cyanotic heart disease, and control group: 26 patients with cyanotic heart disease after biventricular repair). We measured basic fibroblast growth factor, vascular endothelial growth factor (VEGF), hepatocyte growth factor, and endostatin at catheterization. Angiographic evaluation for the presence of APCs using a 4-point scale (grade 1: absent APCs, > or = grade 2: significantly present APCs) was performed, and the relation of the serum levels of these factors to the presence of APCs was assessed. The grade of APCs significantly increased in the Fontan group, but it decreased in the control group. The serum VEGF levels were higher in the Fontan group (280 +/- 174 pg/mL) and the cyanotic group (302 +/- 245 pg/mL) than in the control group (111 +/- 91 pg/mL) (P = .0004), and they were higher in patients with APCs (383 +/- 204 pg/mL) than in those without APCs (115 +/- 65 pg/mL) (P < .0001). There was no significant difference in the serum basic fibroblast growth factor, hepatocyte growth factor, and endostatin levels between the 3 groups. Aortopulmonary collaterals increase after the Fontan procedure. Serum VEGF levels are associated with the presence of APCs. Vascular endothelial growth factor may play a role in the development of APCs in patients with cyanotic heart disease and after the Fontan procedure.
    American heart journal 06/2007; 153(6):987-94. · 4.65 Impact Factor
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    ABSTRACT: The aim of this retrospective study was to evaluate the effectiveness of indomethacin therapy for patent ductus arteriosus (PDA) in full-term infants. The patients were 41 full-term infants with a PDA birth weight (BW) > or =2500 g and a gestational age (GA) > or =37 weeks. The echocardiographic evaluation and medical management of PDA in these infants was similar to that for PDA in low-birth-weight infants. Indomethacin (0.2-0.25 mg/kg/dose) was given intravenously at 12-24-hour intervals within 23 days of birth. Of the 41 infants, 12 showed complete closure, and 13 showed improvement of clinical symptoms. These 25 infants were classified as the responder group (61%). The other 16 infants, who did not show improvement in clinical symptoms, were classified as the nonresponder group. Statistical analysis revealed no difference between the two groups regarding GA, BW, Apgar score at 1 minute, minimum diameter of the DA before treatment, the average age at the initiation of treatment, and DA flow pattern. No severe adverse reactions were observed in any infant. Indomethacin therapy appears to be an effective medical treatment option for PDA in full-term symptomatic infants prior to considering surgical treatment.
    Pediatric Cardiology 01/2007; 28(1):46-50. · 1.20 Impact Factor

Publication Stats

2k Citations
384.15 Total Impact Points

Institutions

  • 2012
    • Toho University
      • Department of Pediatrics
      Edo, Tōkyō, Japan
  • 2009
    • Sakakibara Heart Institute
      Фучу, Tōkyō, Japan
  • 1999–2009
    • Tokyo Women's Medical University
      • • Department of Cardiology
      • • Department of Cardiovascular Surgery
      Edo, Tōkyō, Japan
  • 2008
    • Hokkaido University
      • Department of Pediatrics
      Sapporo-shi, Hokkaido, Japan
  • 2005–2008
    • Chiba University
      • Department of Pediatrics
      Chiba-shi, Chiba-ken, Japan
  • 2004
    • Tokyo Woman's Christian University
      Edo, Tōkyō, Japan
  • 1983–2003
    • Tokyo Junshin Women's College
      • • Department of Pediatric Cardiology
      • • Department of Pediatric Cardiovascular Surgery
      Edo, Tōkyō, Japan
  • 1991
    • Kyushu University
      Hukuoka, Fukuoka, Japan