Background The characteristics and outcomes of patients discharged from hospitals with a diagnosis of heart failure (HF) have been described by a number of previous epidemiological studies. However, very little information is available on this issue in general practice in Japan. Methods and Results The Japanese Cardiac Registry of Heart Failure in General Practice (JCARE-GENERAL) is designed to study the characteristics, treatment and outcomes prospectively in a broad sample of outpatients with HF who were managed by cardiologists in hospital (Hospital-HF) and primary care physicians in general practice (GP-HF). Out of 2,685 patients with HF, 1,280 patients were Hospital-HF and 1,405 GP-HF. Compared to the Hospital-HF patients, GP-HF patients were more likely to be elderly and female, and they had a higher prevalence of hypertensive heart disease as a cause of HF. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and β-blockers were more prescribed to Hospital-HF than GP-HF patients. At the follow-up of 1.2 year, after adjustment, the mortality was comparable between the Hospital-HF and GP-HF groups, whereas HF-related admission was higher in the Hospital-HF group than in in the GP-HF group. Conclusions Based on the JCARE-GENERAL, the characteristics, treatment and outcomes of GP-HF patients differed from those of Hospital-HFpatients in Japan. (Circ J 2007; 71: 449 - 454)

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Background Community based studies of congestive heart failure (HF) are lacking in the Japanese population. Methods and Results To delineate the epidemiological and clinical features of advanced HF in the general Japanese population, hospitalized adult cases of HF in all hospitals within the Ninohe district were registered for 3 years. During the survey period, 190 new onset cases (males n=93; females n=97) and a total of 391 hospitalizations (including repeat admissions) were registered. The prevalence of atrial fibrillation in new HF cases was 56% in males and 45% in females. On the basis of the population of the district, the incidence of hospitalized HF was 96 in males and 92 in females per 100,000 person-years. The percentage of HF patients who were ≥65 years of age was 82% in males and 94% in females. In cases undergoing echocardiography, preserved left ventricular systolic function (left ventricular ejection fraction ≥50%) was observed in 29% of males and 41% of females. There was a significant seasonal variation in HF admissions (Spring 32%; Summer 20%; Autumn 20%; Winter 28%; p<0.01). Conclusions In comparison with published results of USA and European community based studies of HF, the present HF cohort showed that: (1) mean age, prevalence of preserved ejection fraction, and trends in seasonal variation were comparable; however (2) the incidence of HF was obviously lower. These epidemiological and clinical characteristics should be taken into consideration when establishing a therapeutic and preventive approach for HF. (Circ J 2007; 71: 455 - 459)

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Background Resistin is derived from fat tissue in rodents, and serum levels are elevated in animal models of obesity and insulin resistance. Recent studies have reported that resistin is correlated with markers of inflammation and oxidative stress and is predictive of coronary atherosclerosis in humans. However, clinical significance of serum resistin has not been examined in heart failure. Therefore, the purpose of this study was to examine whether: (1) resistin is correlated with the severity of heart failure; and (2) resistin can predict clinical outcomes of patients with heart failure. Methods and Results Serum levels of resistin in 126 patients hospitalized for heart failure and 18 control subjects were measured. The patients were followed up with end-points of cardiac death and re-hospitalization caused by worsening of heart failure. The serum resistin level was higher in patients with heart failure than in control subjects and increased with advancing New York Heart Association functional class. The normal upper limit of the resistin level was determined as the mean +2 standard deviation value of control subjects (14.1 ng/ml). In heart failure patients, the cardiac event rate was higher in patients with a high resistin level than in those with a normal level. Among age, body mass index, serum levels of resistin, brain natriuretic peptide, loop diuretics selected by the univariate Cox regression hazard analysis, age and resistin were significant predictors of future cardiac events by multivariate Cox analysis. Conclusion Serum resistin was related to the severity of heart failure and associated with a high risk for adverse cardiac events in patients with heart failure. (Circ J 2007; 71: 460 - 464)

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Background It is widely known that blood flow redistribution is impaired in patients with chronic heart failure (CHF). However, the relationship between exercise tolerance and the degree of blood flow redistribution is not fully understood. Whole-body thallium-201 chloride (²⁰¹Tl) scintigraphy can estimate blood flow distribution. This study will evaluate the relationship between exercise tolerance and blood flow redistribution using whole-body scintigraphy in patients with CHF. Methods and Results Exercise stress whole-body thallium scintigraphy was performed in 19 patients with CHF (mean ejection fraction: 33.0%; peak oxygen uptake: 15.5 ml · min^-1 · kg^-1). Blood flow redistribution was quantified by comparing the regional thallium count (count/pixel) in the thigh and arm. We then assessed the relationship between these parameters and parameters obtained from cardiopulmonary exercise testing. ²⁰¹Thallium-chloride uptake in the thigh increased during exercise compared to rest (p<0.05), while its uptake in the arm was not different between exercise and rest. Increased ²⁰¹Tl uptake in the thigh during exercise was positively correlated with exercise tolerance (r=0.689). In contrast, ²⁰¹Tl uptake in the arm was not correlated with exercise tolerance. Conclusions By using this method, it is concluded that blood flow redistribution to the exercising muscle increases as the exercise tolerance increases in patients with CHF. (Circ J 2007; 71: 465 - 470)

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Background Prolongation of the action potential duration (APD) is observed in ventricular myocytes isolated from the failing heart. The rapid component (I_Kr) and the slow component (I_Ks) of the delayed-rectifier potassium current (I_K) are major determinants of the APD, but less information is available on the genomic modulation of I_K in the remodeled human heart. The aim of the current study was to examine the relationship between I_K transcripts and QT interval in surface electrocardiogram in patients with chronic heart failure (CHF). Methods and Results Total RNA was extracted from right ventricle endomyocardial biopsy samples in 21 CHF patients (age: 53±4 years, mean ± SEM). The KCNH2 and KCNQ1 levels did not differ significantly between controls (New York Heart Association (NYHA) I, n=10) and CHF patients (NYHA II or III, n=11), whereas the KCNE1 level was significantly higher in CHF patients than in controls (relative mRNA levels normalized to GAPDH expression: 6.16±0.31 vs 7.70±0.46, p<0.05). The KCNE1/KCNQ1 ratio was higher in CHF patients than in controls (0.92±0.02 vs 1.06±0.05, p<0.05) and the KCNE1 - KCNQ1 ratio was positively correlated with QT interval (r=0.70, p<0.05). Increasing the KCNE1 concentration caused a shift in activation voltage and slowed the activation kinetics of the KCNE1 - KCNQ1 currents expressed in Xenopus oocytes. Prolongation of the APD and decrease in I_Ks with increasing the amount of KCNE1 concentration were well predicted in a computer simulation. Conclusions In mild-to-moderate CHF patients, the relative abundance of KCNE1 compared to KCNQ1 genes, at least in part, might contribute to the preferential prolongation of QT interval through reducing the net outward current during the plateau of the action potential. (Circ J 2007; 71: 471 -478)

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Background The association of white blood cell (WBC) count with all-cause and cardiovascular disease (CVD) mortality were examined in the National Integrated Project for Prospective Observation of Non-communicable Disease and Its Trends in the Aged (NIPPON DATA) 90. Methods and Results A total of 6,756 Japanese residents (2,773 men and 3,983 women) throughout Japan without a history of CVD were followed for 9.6 years. A Cox proportional hazards regression model was used to estimate the relative risk (RR) and 95% confidence interval (CI). We documented 576 deaths with 161 deaths from CVD. Overall, after adjusting for several confounders including age, sex, body mass index at baseline, smoking status, alcohol consumption, regular exercise, diastlic blood pressure, total cholesterol, high-density lipoprotein-cholesterol and hemoglobin A1c, a graded association between WBC count and higher risk of all-cause mortality was observed (WBC of 9,000-10,000 cells/mm³ vs WBC of 4,000-4,900: RR =1.61, 95% CI: 1.07-2.40, p for trend =0.02). Elevated WBC count was almost significantly associated with high risk of CVD mortality (WBC of 9,000-10,000 vs WBC of 4,000-4,900: RR =1.79, 95% CI: 0.97-3.71). These associations strengthened among women. Stratified by smoking status, never-smokers with WBC counts of 9,000-10,000 had a 3.2 fold elevated risk for CVD death compared with those with WBC counts of 4,000-4,900. Conclusions The WBC count may have potential as a predictor for all-cause mortality, particularly CVD mortality. (Circ J 2007; 71: 479 - 485)

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Background Recently the potential of myocardial repair by transplantation of autologous bone marrow stem cells has been suggested. Whether the additional intracoronary transplantation of autologous peripheral blood stem cells (PBSC), which were mobilized by granulocyte-colony-stimulating factor (G-CSF), could safely improve myocardial function in patients with acute myocardial infarction (AMI) was investigated. Methods and Results Seventy-three patients with AMI who had successfully undergone percutaneous coronary intervention (PCI) were enrolled in the present prospective nonrandomized open-labeled study. Ten patients with elective PCI received G-CSF for 4 days followed by intracoronary PBSC transplantation. Thirty-two patients with primary PCI and 31 patients with recent AMI and elective PCI served as controls. The left ventricular (LV) function was evaluated using echocardiography and magnetic resonance imaging. G-CSF and intracoronary transplantation of PBSC did not incur any periprocedural myocardial damage. After 6 months, the LV ejection fraction was significantly improved in the cell therapy group. For 2 years of the follow-up period, there was no adverse clinical events, except one asymptomatic in-stent restenosis. However, comparable improvement of the LV ejection fraction was also identified in the primary PCI and elective PCI control groups. Conclusions In the present study, additional intracoronary infusion of PBSC was safe and feasible for the patients with AMI who had undergone PCI, but did not lead to a significant improvement in LV function compared to standard reperfusion treatment. (Circ J 2007; 71: 486 - 494)

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Background Recently, a large case-control study (2,851 cases and 2,592 controls) reported that a functional single nuclear polymorphism (SNP) in the proteasome subunit α type 6 gene (PSMA6) conferred a risk of myocardial infarction (MI) in a Japanese population. The SNP (exon 1, -8C/G) is located in the 5' untranslated region of exon 1, and the risk-conferring allele G appears to enhance the transcription of PSMA6, which may exaggerate inflammation through activation of nuclear factor-κ β protein. The frequency of the risk conferring genotype (GG) in cases was reported to be greater than that in controls (12.4% vs 8.9%). The purpose of the present study was to validate this observation in our study population. Methods and Results Subjects with MI (n=433) were recruited from the outpatient clinic of the National Cardiovascular Center. Control subjects (n=2,186) were recruited from the Suita study. The frequencies of the GG genotype did not significantly differ between the control (9.8%) and MI groups (10.6%). Moreover, this genotype was not associated with C reactive protein levels in the Suita study. However, the GG genotype was significantly associated with greater intima-media thickness (n=2,051, p=0.015) after adjusting for blood pressure, sex, body mass index and age in the Suita study. Conclusion The reported genotype in PSMA6 appears not to contribute appreciably to MI, but may contribute slightly to atherosclerosis in the present study population. (Circ J 2007; 71: 495 - 498)

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Background It is unclear whether coronary artery stenosis affects the secretion of N-terminal pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) from the heart independent of ventricular dysfunction. Therefore, this study evaluated the relationship between BNP and NT-proBNP secretion, plasma levels and the severity of coronary artery stenosis in patients with stable coronary artery disease (CAD). Methods and Results Plasma levels of BNP and NT-proBNP in the aortic root (AO) and coronary sinus (CS) in 251 consecutive patients with stable CAD were measured. The transcardiac increase of NT-proBNP was significantly increased with the severity of coronary artery stenosis (p=0.012), but that of BNP was not (p=0.116). The molar ratio of the (CS-AO) NT-pro-BNP/(CS-AO) BNP increased with the severity of coronary artery stenosis (p=0.019) and decreased after coronary revascularization (p=0.018, n=36). Step-wise multivariate linear regression analyses were used to detect independent predictors of the (CS-AO) NT-proBNP among 10 variables including hemodynamic parameters and the Gensini score, which is a measure of the extent and severity of CAD. Among these variables, left ventricular ejection fraction (p<0.0001), left ventricular end-diastolic pressure (p=0.003) and log Gensini score (p=0.008) were significant independent predictors. Conclusion These findings suggest that the transcardiac increase of NT-proBNP from the heart increases with the severity of coronary artery stenosis independent of hemodynamic overload, and plasma NT-proBNP may be superior to BNP to assess disease severity in CAD patients. (Circ J 2007; 71: 499 - 505)

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Background The purpose of the present study was to investigate the elastic characteristics of the aorta in patients with coronary ectasia (CE) and the relationship between these characteristics and echocardiographic left ventricular (LV) diastolic functions. Methods and Results In the first group there were 35 patients with CE, the second group consisted of 35 patients with coronary artery disease (CAD) and the third group consisted of 35 patients with normal coronary arteries. Echocardiographic investigation was carried out for the assessment of the LV diastolic functions. Aortic strain, β index and aortic distensibility were used as aortic elasticity parameters. LV diastolic functions were impaired in both the ectasia group and the CAD group as compared with patients with normal coronary arteries. Beta index and aortic distensibility measurements were similar between the CAD and CE groups. The values obtained for aortic strain, β index and aortic distensibility were lower in the CAD and ectasia groups when compared with the values of the normal group. On performing the stepwise linear multivariable analyses, aortic elastic parameters have been determined to possess the strongest diagnostic power for LV diastolic functions. Conclusions The results of the current study show that stiffness parameters of aorta are impaired in the patients with CE as in the patients with CAD. The increase in aortic stiffness might be responsible for LV diastolic dysfunction. (Circ J 2007; 71: 506 - 510)

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Background The timing of referral to nephrologists is highly variable in patients with chronic kidney disease (CKD). The impact of early referral on the timing of hemodialysis (HD) and mortality in the patients with CKD and cardiovascular diseases (CVD) was evaluated in this present study. Methods and Results A total of 366 patients with CKD and CVD began HD at the National Cardiovascular Center between 1983 and 2003, and survival was followed until 2005. The times between the first evaluation by a nephrologist and the date of the first HD were categorized as late (LR <6 months) or early (ER ≥6 months) referral. Patients were classified into the ER (n=194) and LR (n=172) groups. Clinical data and renal function were not different. In the LR group, the renal function declined more rapidly and the duration between the first visit to the hospital and the first HD was shorter than the ER group. The survival rate after the initiation of HD was better in the ER group. Age, pre end-stage renal disease therapy and cardiac function had a significant impact on survival. Conclusions Early nephrology referral is important and necessary for for patients with CKD and CVD in terms of a better renal prognosis and survival. (Circ J 2007; 71: 511 - 516)

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Background The relationship between regional and global left ventricular function has not been evaluated. The present study aimed to assess whether regional myocardial contraction and relaxation reflect global left ventricular systolic and early diastolic function, respectively. Methods and Results The study involved 45 patients with coronary artery disease (CAD). Conventional echocardiography was performed, and segmental peak strain rate (SR) in the systole (S_SR) and early diastole (E_SR) were obtained from tissue Doppler imaging in each of 18 segments of the left ventricular myocardium from the apical views. The E_SR was significantly correlated with S_SR in all studied segments (r=0.55, p<0.0001). The average values of SR indices in each patient were defined as S_SR index and E_SR index, which were derived by dividing the summed value of the S_SR or E_SR by the number of respective assessable segments. A significant positive relationship was observed between the S_SR index and left ventricular ejection fraction (r=0.85, p<0.0001). Also, there was a positive correlation between the E_SR index and mitral flow E (r=0.68, p<0.0001). Conclusions Regional myocardial contraction and relaxation, as assessed by SR imaging, were closely related in patients with CAD. Furthermore, regional myocardial contraction and relaxation are important factors affecting global left ventricular systolic and early diastolic function. (Circ J 2007; 71: 517 - 523)

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Background We attempted to test the hypothesis that chronic angiotensin II type 1A receptor blockade (ARB) alters myocardial collagen turnover leading to an improvement of diastolic dysfunction in diabetic patients. Methods and Results Forty-eight type 2 diabetic patients were divided into 2 groups: 38 treated with candesartan for 6 months, and 10 without candesartan, as controls. Doppler mitral flow velocity pattern and biomarkers of collagen type I turnover were assessed before and after ARB during a 6-month period. The mitral E/A ratio increased from 0.65±0.11 to 0.75±0.19. The carboxy-terminal propeptide of procollagen type I (PIP), an index of collagen type I synthesis, decreased and the carboxy-terminal telopeptide of collagen type I (CITP), an index of collagen type I degradation, increased following ARB. Consequently, the PIP/CITP ratio, an index of coupling between the synthesis and degradation of collagen type I, decreased. None of the indexes changed in the control group. The change in left ventricular chamber stiffness did not correlate with the change in PICP (r=0.08, p=NS), but it did with the changes in CITP or in the PIP/CITP ratio (r=0.35, p<0.05; r=0.39, p<0.05). Conclusions Chronic ARB improves diastolic dysfunction in diabetic patients, at least partially through the attenuation of myocardial fibrosis, by regulating collagen turnover, particularly by facilitating collagen degradation. (Circ J 2007; 71: 524 - 529)

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Background Previous intravascular ultrasound (IVUS) studies have shown that calcification can be quantified by the determination of the arc on one cross-section. However, because calcium levels change along the length of lesions, it is important to assess the length of calcium using serial cross-sectional images. The correlation between the largest arc and length of each calcium deposit in patients with coronary artery disease (CAD) has not been determined. The present study was performed to determine this correlation. Methods and Results Preinterventional IVUS images of 194 patients with CAD were studied. The largest arc and length of all calcium within the 10-mm-long culprit lesion segment were quantified using serial cross-sectional images. One hundred and ninety-four patients had 277 calcium deposits. In all patients, the length of each calcium exhibited a strong correlation with the largest arc of calcium (R=0.750, p<0.0001). Conclusions Our findings revealed the quantitative characteristics of each calcium within the culprit lesion segment. They will be useful in interpreting results of previous and future IVUS studies, which deal only with the arc of calcium, as well as studies using new modalities such as computed tomography that assess calcium mainly along the long axis of the coronary artery. (Circ J 2007; 71: 530 - 535)

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Background The association between epicardial fat and coronary artery disease has not been evaluated. The objective of the present study was to evaluate the relationship of echocardiographic epicardial fat to the presence and severity of coronary artery disease in a clinical setting. Methods and Results Two hundred and three consecutive patients who underwent echocardiography and diagnostic coronary angiography were studied. The epicardial fat thickness on the free wall of the right ventricle was measured at end-diastole from the parasternal long-axis views of 3 cardiac cycles. Coronary angiograms were analyzed for the extent and severity of coronary artery disease using Gensini's score. The patients were divided into 2 groups according to the fourth quartile of epicardial fat thickness (Group I <7.6 mm; Group II ≥7.6 mm). There were no significant differences in the baseline characteristics except for waist circumference (p=0.023). Significant correlations were demonstrated between epicardial fat thickness and age (r=0.332, p<0.001), C-reactive protein (r=0.182, p=0.009), body mass index (r=0.142, p=0.044) and waist circumference (r=0.229, p=0.001). The patients with a higher epicardial fat thickness were associated with a high Gensini's score (p=0.014). Multivariate analysis showed that age (odds ratio (OR) 5.29, p=0.003), epicardial fat thickness (OR 10.53, p=0.004), diabetes (OR 8.06, p=0.006) and smoking (OR 14.65, p=0.015) were independent factors affecting significant coronary artery stenosis. Conclusions Epicardial fat thickness was significantly correlated with the severity of coronary artery disease in patients with known coronary artery disease. (Circ J 2007; 71: 536 - 539)

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Background Electrocardiographic conduction abnormalities including development of atrioventricular block, bundle branch block or ventricular arrhythmias are characteristic manifestations of cardiac sarcoidosis (CS). The present study seeks to show the minute conduction abnormality by detection of late potentials (LP) on signal averaged electrocardiogram (SAECG). Methods and Results Ten patients with CS, 52 patients with pulmonary sarcoidosis (PS) but no obvious cardiac manifestations and 52 normal controls were studied. All participants underwent SAECG to detect LP. In patients with CS (the CS group), LP were detected in 8 patients (80%). In 52 patients with PS, LP were detected in 25 patients (46.2%, PS-LP(+) group), comparing only 3 (5.8%) of normal controls (p<0.0001). The remaining 27 patients with PS with negative LP were classified in the PS-LP(-) group. In the CS group, premature ventricular contraction frequency on Holter's monitoring and plasma B-type natriuretic peptide concentrations were significantly higher than those in the PS group. However, no significant difference in these parameters between PS-LP(+) and PS-LP(-) groups were found. Conclusions In the PS patients without obvious cardiac manifestations, LP were detected as high as 46.2%, suggesting latent minute conduction abnormality. The higher incidence of LP in PS might be considered as an expression of latent myocardial fibrosis. Close follow-up is needed in these patients. (Circ J 2007; 71: 540 - 545)

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Background In the clinical situation, the saddle-back (S-B) type is more frequently detected than the coved type. In the present study, the discrimination of Brugada syndrome from the S-B type individuals using a marker of the standard 12-lead electrocardiography (ECG) was attempted. Methods and Results The study group consisted of 55 individuals with the S-B type in whom pilsicainide provocation test (PLC test) was carried out. The time from the onset of the QRS wave in lead V₂ (IV ₂) to the peak of the late R-like wave in the QRS wave (PV₂), and the time from IV₂ to the offset of the QRS wave in lead V₅ (EV₅) were measured. The coved type was induced by the PLC test in 29 cases (N-C group), but not in the remaining 26 cases (N-N group). The (IV₂ -PV₂) - (IV₂ - EV₅) value before the PLS test was greater in the N-C group than in the N-N group. The negative predictive value of `(IV<sub>2</sub> - PV<sub>2</sub>) - (IV<sub>2</sub> - EV<sub>5</sub>) ≥0' was 76.4% for the prediction of a positive PLC test. Conclusions A `(IV₂ - PV₂) - (IV₂ - EV₅) ≥0' is a useful ECG marker for the discrimination of Brugada syndrome in the S-B type individuals. (Circ J 2007; 71: 546 - 549)

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Background Prehypertension is a new category of blood pressure (BP) classification according to the Seventh Report of The Joint National Committee. Little is known about the epidemiology of prehypertension in rural China. The purpose of the present study is to determine the prevalence of prehypertension and associated risk factors in rural adult people of China. Methods and Results Through cluster multistage and random sampling method, a resident group of 29,970 people aged ≥35 years old in Liaoning Province was selected from 2004 to 2005. The survey on BP and associated risk factors was carried out. Prehypertension was defined as systolic BP between 120 and 139 mmHg or diastolic BP 80 and 89 mmHg. Overall, the prevalence of prehypertension was 47.0%, males 51.2% and females 42.6%, respectively. The prevalence of hypertension was 36.2%. Multivariable logistic regression showed overweightness, obesity and drinking were risk factors of prehypertension. Female and greater than high school education status were shown as protective factors. Conclusions The prevalence of prehypertension of rural adult people in China is dramatically high and it was associated with many risk factors. Comprehensive lifestyle modifications are needed to be taken to decrease the incidence of prehypertension and to prevent prehypertension people from hypertension and cardiovascular disease. (Circ J 2007; 71: 550 - 553)

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Background To evaluate the use and advantage of microsurgical intervention and intravenous iloprost administration in delayed infantile artery injuries. Methods and Results Four patients were followed up and treated in our clinic between June 2003 and June 2006 for infantile artery injuries and distal ischemia. The average age of the 4 infants (3 girls, 1 boy) was 134.7±33.6 days. The reason for all of the artery injuries was iatrogenic. Tissue necrosis started in patches in 2 babies who were admitted at the 12^th hour after ischemia (19^th and 22^nd hours), and therefore the artery was repaired by microsurgery. Iloprost infusion was also used in addition to the conservative treatments. The other 2 patients were assessed before the first 12 h after distal ischemia and were treated by iloprost without any surgical intervention. None of the patients lost any tissue or extremities during the 9 months (average) follow-up time. One of our patients died following the ventricular septal defect repair at the 9^th month after a successful repair of artery. Discussion We believe that intravenous iloprost infusion is very effective in the treatment of distal ischemia when used in addition to the conservative treatment methods for artery injuries in infants. (Circ J 2007; 71: 554 - 558)

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Background Most of the patients with pulmonary arterial hypertension (PAH) receiving intravenous epoprostenol have experienced catheter-related infections during long-term treatment. Catheter hub was reported to be the most important source of catheter-related infections. To prevent the catheter-related infections, we have introduced a closed hub system and compared the incidence of catheter-related infections with that in patients using a non-closed hub system. Methods and Results We evaluated the results obtained on 24 occasions in 20 patients with PAH between June 1999 and December 2005. On 11 occasions, a non-closed hub system was used and on 13 cases a closed hub system. We classified the catheter-related infection into a catheter-related bloodstream infection (CRBSI) group or a tunnel infection group based on the pathway of bacteria. The CRBSI rate was 0.89 per 1,000 catheter days in the non-closed hub system group vs 0.10 per 1,000 catheter days in the closed hub system group. Kaplan - Meier analysis showed that the risk of CRBSI significantly decreased in the closed hub system group. None of the patients died as a direct consequence of catheter-related infection during the study period. Conclusions We successfully prevented CRBSI by using a closed hub system. (Circ J 2007; 71: 559 - 564)

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Background Takotsubo cardiomyopathy is triggered by emotional or physical stress especially in post-menopausal women. A reduction in estrogen levels following menopause might underlie the high incidence of takotsubo cardiomyopathy. Methods and Results The left ventricular contraction between ovariectomized rats (OVX) and OVX with estrogen supplementation (OVX + E) while subjected to immobilization stress (IMO) was compared. The IMO in combination with general anesthesia impaired the left ventricular contraction in both OVX and OVX + E. Estrogen supplementation tended to improve the IMO-induced cardiac dysfunction and significantly attenuated the increase of blood pressure and heart rate. To understand the protective mechanism of estrogen, the expression of c-fos mRNA, a marker of cellular activation was compared. The mRNA expression of cardioprotective substances in the heart was also investigated. In the OVX + E, the levels of c-fos mRNA were significantly decreased in the paraventricular hypothalamic nucleus, adrenal gland and left ventricle, suggesting that an increase of estrogen attenuates the emotional stress-induced hypothalamo-sympatho-adrenal outflow from the central nervous system to the target organs. An expression of heat shock protein 70 and atrial natriuretic peptide was significantly augmented in the OVX + E. Conclusions These data suggest that estrogen supplementation partially prevents emotional stress-induced cardiovascular responses both by indirect action on the nervous system and by direct action on the heart. (Circ J 2007; 71: 565 - 573)

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Background It is still unclear whether celiprolol, a β₁-selective blocker, reduces myocardial infarct size. This study will examine whether celiprolol reduces myocardial infarct size, as well as investigate the mechanisms for its infarct size-reducing effect in rabbits. Methods and Results Japanese white rabbits underwent 30 min of ischemia and 48 h of reperfusion. Celiprolol (1 or 10 mg · kg ^-1 · h^-1 for 60 min, iv) was administered 20 min before ischemia with or without pretreatment with N^ω-nitro-L-arginine methylester (L-NAME, 10 mg/kg, iv, a nitric oxide synthase inhibitor) or 5-hydroxydecanoic acid sodium salt (5-HD, 5 mg/kg, iv, a mitochondrial K_ATP channel blocker). The area at risk as a percentage of the left ventricle was determined by using Evens blue dye, and the infarct size was determined as a percentage of the area at risk by triphenyl tetrazolium chloride staining. Celiprolol 1 and 10 mg · kg^-1 · h^-1 significantly reduced the infarct size in a dose-dependent manner (36.4±1.7%, n=7 and 25.4±2.9%, n=7, respectively) compared with the control (46.2±3.1%, n=8). The infarct size-reducing effect of celiprolol was completely blocked by L-NAME (40.4 ±2.8%, n=8) but not by 5-HD (27.3±1.0%, n=8). Celiprolol 1 mg · kg^-1 · h ^-1 increased the myocardial interstitial levels of NOx, an indicator of nitric oxide, and reduced the intensity of dihydroetidium staining of myocardium, an indicator of superoxide, during reperfusion after 30 min of ischemia. Conclusion Celiprolol reduces myocardial infarct size and also increases nitric oxide production and reduces superoxide levels but not mitochondrial K_ATP channels in rabbits. (Circ J 2007; 71: 574 - 579)

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Background The purpose of the present study was to investigate the effect of granulocyte colony-stimulating factor (G-CSF) in combination with myelosuppressives on post-myocardial infarction (MI) myocardial repair. Methods and Results Twenty-four hours after 30-min ischemia and reperfusion (day 0), rabbits were assigned to 4 treatment groups: myelosuppressives (M group), G-CSF (G group), the 2 in combination (MG group) or saline (S group). Significantly greater numbers of circulating stem cells were seen in the MG group than in the G group, with attenuated leukocytosis. In addition, MG caused the greatest upregulation of stromal cell-derived factor (SDF)-1 within the infarcted myocardium and thus recruitment of stem cells from the circulation into the infarcted tissue. This led to enhanced myocardial repair, as indicated by the numbers of bone marrow cell-derived cardiomyocytes and endothelial cells, reduction in scar tissue, improvement in cardiac function and reduction in left ventricular remodeling during the chronic phase of MI. These beneficial effects were entirely abolished by the administration of a CXCR4 antagonist AMD3100, which indicates the importance of CXCR4/SDF-1-axis as a mechanism underlying myocardial repair. Conclusion The combination of G-CSF and myelosuppressives may be a useful new therapy that overcomes the insufficiency seen with G-CSF alone. (Circ J 2007; 71: 580 - 590)

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Background Remote reperfusion lung injury occurs in patients with vascular occlusion and surgical procedures. Inosine monophosphate (IMP) produced by adenosine monophosphate deaminase (AMPD) 3 is involved in the remote reperfusion injury. The purpose of the present study was to identify whether IMP administration attenuated the remote reperfusion lung injury in a skeletal muscle ischemia-reperfusion model. Methods and Results A remote reperfusion lung injury was created using reperfusion after the bilateral ligation of the hind-limb. AMPD activity, myeloperoxidase (MPO) activity, IMP, AMPD3 mRNA and tumor necrosis factor (TNF)-α in the lungs before and after reperfusion were analyzed. Furthermore, the effects of IMP on these parameters were examined. AMPD3 mRNA, AMPD activity and IMP production in the lungs significantly increased after ischemia-reperfusion with increases in MPO activity, TNF-α level and decreased oxygen saturation (SpO₂). Histological examination of the lungs demonstrated significant neutrophil infiltration and accumulation. IMP administration significantly reduced MPO activity, TNF-α and neutrophil infiltration, with ameliorated SpO₂. Conclusions Along with the activation of AMPD3, ischemia-reperfusion-induced lung inflammation is associated with increased MPO activity and TNF-α level. IMP significantly decreased the lung injury, MPO activity, TNF-α and increased SpO₂. These findings may lead to the development of a new therapeutic strategy for remote reperfusion lung injury. (Circ J 2007; 71: 591 - 596)

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Background Epigallocatechin-3-gallate (EGCG) is the most potent antioxidant of all the green tea catechins. The objective of the present study was to find out whether it improved the age-induced hemorheological abnormalities or not. Methods and Results Twenty-four-month-old aging guinea pigs were used to test the effects of EGCG on hemorheolohgical properties. Orally feeding EGCG at 30 mg · kg^-1 · day ^-1 for 28 days resulted in a decrease in erythrocyte membrane malondialdehyde, and further improved erythrocyte deformability and blood viscosity at high and middle shear rates. In addition, it also significantly reduced erythrocyte aggregation, and improved blood viscosity at low shear rates and viscoelasticity at oscillatory flow. Consequently, efficiency of blood oxygen transport in aged guinea pigs increased after administration with EGCG. Conclusions Orally feeding EGCG 30 mg · kg^-1 · day^-1 for 28 days significantly improves the abnormal hemorheological parameters. These results suggest that EGCG has considerable potential as a substantial component for the development of new drugs or functional foods in improving the age-induced hemorheological abnormalities. (Circ J 2007; 71: 597 - 603)

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Patients with a left atrial (LA) thrombus are considered at high risk of thromboembolic events. Reports about thrombolytic therapy are limited and optimal guidelines are lacking. In this report, a large, pedunculated, highly mobile thrombus of the LA attached via a short stalk to the LA appendage brim in a 59-year-old female with atrial fibrillation is described. The patient was treated with 100 mg intravenous tissue plasminogen activator for 2 h after the ineffective administration of herapin. The thrombus soon dissolved. However, the patient developed a transient ischemic embolism 12 h later when the post hoc heparin effect was at its nadir. Based on this and other reports, thrombolytic therapy may be effective and safe in patients with acute, non-organized LA thrombi and post hoc heparinization should be sufficient to prevent thromboembolism from rebound coagulation. (Circ J 2007; 71: 604 -607)

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Dynamic intraventricular obstruction is a less well-known mechanical complication of acute myocardial infarction (AMI). Its hallmark is the development of a new systolic murmur, and echocardiography is necessary for diagnosis. We describe a case of a 74-year-old woman with dynamic intraventricular obstruction complicating AMI. Serial echocardiography suggested that the intraventricular gradient was a consequence of basal hyperkinesis, which was a reciprocal response to akinesis of the apical wall. Cilostazol, which was administered to prevent subacute stent thrombosis after percutaneous coronary intervention, might have contributed to the transient intraventricular obstruction. (Circ J 2007; 71: 608 - 612)

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Left ventricular (LV) retraining followed by anatomical repair would be a superior alternative in patients with congenitally corrected transposition (ccTGA) having a deconditioned morphologically left ventricle (MLV); however, LV retraining in older children is a challenging task. A retraining process of the MLV in a teenage patient with ccTGA is reported here. Cardiac catheterization at 7 years of age revealed low pressure of the MLV (33/4 mm Hg) and a LV to right ventricular pressure ratio (LVp/RVp ratio) of 0.32. The first pulmonary artery banding (PAB) was performed at 10 years of age. Although the LVp/RVp ratio reached 0.68, there was no evidence of adequate LV hypertrophy. The second PAB was performed 2 years after the initial PAB, resulting in an increase in the LVp/RVp ratio to 0.93 and an adequate LV hypertrophy. The double switch procedure was successfully performed at 13 years of age. Although the ejection fraction of the MLV mildly decreased, the patient has been doing well during a follow-up period of 4 years. The MLV in the teenage patient with ccTGA was successfully trained using a retraining strategy and has sustained systemic circulation after anatomical repair. (Circ J 2007; 71: 613 - 616)

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Background Because of its side-effects, long-term administration of ticlopidine limits the use of the sirolimus-eluting stent (SES) in Japan. Methods and Results Side-effects of ticlopidine occurred in 41 (9.3%) of 440 patients who underwent SES implantation. The majority were liver dysfunction (4.5%) and rash (3.6%). One patient died from severe liver dysfunction. Neutropenia occurred in 3 patients (0.7%). It is remarkable that 28% of side-effects occurred >8 weeks after the initiation of ticlopidine. Conclusions Ticlopidine has a relative high rate of side-effects. Clopidogrel should be approved for prevention of stent thrombosis as soon as possible. (Circ J 2007; 71: 617 - 619)

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