Background Several clinical studies have demonstrated an inverse relationship between hospital volume of primary percutaneous coronary interventions (PCI) and in-hospital mortality. However, the relationships among hospital primary PCI volume, angiographic results, and in-hospital prognosis in patients with acute myocardial infarction (AMI) have not been fully investigated in Japan. Methods and Results Using the AMI-Kyoto Multi-Center Risk Study database between January 2000 and December 2005, hospitals were classified into quintiles based on their annual volume of primary PCI. The fifth quintile of hospitals was labeled as high-volume, and the other quintiles were combined and defined as low-volume. Although patients undergoing primary PCI in high-volume hospitals (high-volume group, n=764) had a larger number of diseased vessels at initial coronary angiography and lower Thrombolysis In Myocardial Infarction (TIMI) flow grade in the infarct-related artery before PCI, compared with those in low-volume hospitals (low-volume group, n=1,021), the rates of achieving TIMI flow grade 3 just after PCI in the high-volume group was significantly higher than that in the low-volume group. The overall in-hospital mortality did not differ between the 2 groups. On multivariate analysis, in AMI patients undergoing primary PCI, Killip class ≥3 at admission, multivessel disease or left main trunk (LMT) as culprit lesion, number of diseased vessels ≥2 or diseased LMT, and age were the independent positive predictors of in-hospital mortality, whereas the TIMI flow grade 3 after primary PCI and elapsed time <24 h were the negative ones, but not low-volume hospital. Conclusions Angiographic results of primary PCI in high-volume hospitals were superior to those in low-volume hospitals, but there was no significant difference in the in-hospital mortality between AMI patients in high-volume hospitals and those in low-volume hospitals. (Circ J 2008; 72: 1041 - 1046)

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Background The impact of ST-segment elevation resolution in lead aVR on outcomes in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) is unclear. Methods and Results Electrocardigrams (ECGs) were recorded on admission and 6 h later in 367 patients with NSTE-ACS. ST-segment deviation ≥0.5 mm was considered significant: 92 patients had ST-segment elevation in lead aVR on admission ECG (ST↑aVR), and 275 did not. Among patients with ST↑aVR, 50 had ST resolution, defined as a reduction >50% in the degree of ST-segment elevation in lead aVR from admission to 6 h later, and 42 did not. ST↑aVR without ST resolution was associated with older age, greater ST-segment depression in other leads on admission and 6 h later, higher rates of positive troponin T, left main and/or 3-vessel coronary disease, and adverse events such as death, (re)infarction, or urgent revascularization within 30 days after admission. Multivariate analysis showed that ST↑aVR without ST resolution was the strongest independent predictor of death or (re)infarction within 30 days after admission (hazard ratio 5.62, p=0.018). Conclusions ST↑aVR without ST resolution is a strong predictor of 30-day adverse outcomes and correlates with the extent and severity of coronary artery disease in patients with NSTE-ACS. (Circ J 2008; 72: 1047 - 1053)

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Background Sirolimus-eluting stents (SES) reduce restenosis and revascularization rates, compared with bare-metal stents (BMS), in elective percutaneous coronary intervention (PCI). This study investigated the safety and efficacy of SES for emergency PCI in acute coronary syndrome (ACS) patients. Methods and Results The 154 consecutive patients (SES: n=77, BMS: n=77) admitted to hospital with ACS were enrolled in this study. Procedural success (%DS <50%, Thrombolysis In Myocardial Infarction grade 3), major adverse cardiac events (MACE) at 30 days and 8 months, and the incidence of stent thrombosis were evaluated. There was no difference between the groups regarding procedural success. Patients treated with SES had smaller stent diameter (SES 3.04 mm vs BMS 3.24 mm; p=0.01) and longer stent length (25.7 mm vs 21.2 mm; p=0.01). At 30 days, there was no difference between the groups in the incidence of cardiovascular events. At 8 months, patients treated with the SES had a lower rate of repeat PCI (5.6% vs 18.6%; p=0.04) and MACE (9.7% vs 27.1%; p=0.01). Stent thrombosis was no different between groups (1.4% vs 2.9%). Conclusion In emergency PCI for ACS patients, SES implantation significantly reduced cardiovascular events, compared with BMS, by decreasing the incidence of repeat PCI. The safety profile of SES is equal to that of BMS. (Circ J 2008; 72: 1054 - 1058)

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Background Small dense low-density lipoprotein (LDL) has emerged as an important risk factor in coronary atherosclerosis and vascular inflammation, which is related to neointimal hyperplasia. Therefore, the aim of the present study was to investigate whether changes in LDL particle size are related to in-stent restenosis (ISR). Methods and Results The LDL subfraction and lipid profiles were measured in 274 patients (412 stents) at both baseline and follow-up coronary angiography (CAG). The incidence of ISR (80 lesions, 19.4%) was lower in the patients with increased LDL particle size than in those with no change or decrease (14.2% vs 25.8%, p=0.004). Logistic multivariate analysis revealed that stent length (≥24 mm) (odds ratio (OR) =1.913, p=0.027), post minimal luminal diameter (>3 mm) (OR =0.528, p=0.028), acute coronary syndrome (OR =2.294, p=0.005), decrease in high-density lipoprotein-cholesterol (OR =1.028, p=0.047) and increase in LDL particle size (OR =0.528, p=0.031) were independent predictors for ISR. Conclusions In the present study, an increase in the LDL particle size between baseline and follow-up CAG was associated with reduced incidence of ISR. Therefore, modification of LDL particle size may have a beneficial effect on the risk of ISR. (Circ J 2008; 72: 1059 - 1064)

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Background T-1131C, T1259C and IVS3+G476A are naturally occurring variants of the apolipoprotein A5 (APOA5) gene and their possible impact on the development of ischemic stroke was investigated in the present study. Methods and Results PCR-RFLP assays were used to determine the distributions of the APOA5 alleles in small-vessel, large-vessel and mixed subgroups of 378 patients and in 131 stroke-free control subjects. Increased triglyceride levels were found in subjects carrying -1131C, 1259C, IVS3+476A alleles in all stroke groups and in the controls. The -1131C and IVS3+476A alleles, but not the T1259C variant, showed significant accumulation in all stroke subgroups. Logistic regression analysis adjusted for age, gender, body mass index, total cholesterol level, ischemic heart disease, hypertension, diabetes mellitus, smoking-and drinking habits revealed that the IVS3+476A allele represents independent susceptibility factor for stroke (odds ratio for small-vessel: 4.748; large-vessel: 3.905; mixed: 2.926; overall: 3.644 at 95% confidence interval; p<0.05), we could also confirm the previously verified pathogenic role of the -1131C variant. Conclusions All of the 3 APOA5 variants are associated with elevated triglycerides, but only the -1131C and the IVS3+476A alleles confer risk for all types of ischemic stroke; such an association could not be detected for the 1259C allele. (Circ J 2008; 72: 1065 - 1070)

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Background ECG-gating is necessary for cardiac computed tomography, but is not suitable for arrhythmias, so the aim of this study was to evaluate the usefulness of the ECG-edit function for this purpose. Methods and Results Of 1,221 patients undergoing 64-row multidetector-row computed tomography coronary angiography (coronary MDCT), 123 patients (28 atrial fibrillation (Af), 39 premature atrial contractions (PAC), 42 premature ventricular contractions (PVC), 3 PAC + PVC, 10 sinus arrhythmias (SA), and a second-degree atrioventricular block (2°AVB)) had arrhythmias necessitating the ECG-edit function. Short R-R interval was deleted and mid-diastolic phases were selected from the long R-R intervals using the "R+absolute time" method. In the present study, the reconstructed images were evaluated using a triple-grade scale A-C, representing excellent, acceptable, and unacceptable image quality. Image quality, categorized as A, B and C, respectively, was 50%, 36% and 14% for the 28 patients with Af; 56%, 36% and 8% for the 39 PAC patients, and 65%, 33% and 2% in the 42 PVC patients. None of the scans of the PAC + PVC, SA, and 2°AVB patients was ranked as C. Conclusions The ECG-edit function is useful for reconstructing coronary MDCT images in many arrhythmias, and provides clinically acceptable images in most cases. (Circ J 2008; 72: 1071 - 1078)

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Background The diagnosis of myocardial bridging (MB) is of clinical importance because of the association between MB and compromised coronary flow. The aim of this study was to compare the ability of dual-source computed tomography (DSCT) and conventional coronary angiography (CAG) to detect MB. Methods and Results DSCT were performed in 53 patients and 4-dimensional (D) reconstruction was subsequently performed in 16 patients with MB for double-blinded comparison with the findings of CAG. The diameters at systole and diastole of the coronary segments proximal and distal to the MB and of the tunneled segment were measured. The relationship between the rate of stenosis of the tunneled artery and the "milking" effect on 4-D reconstruction was analyzed. Of the 53 patients, CAG and DSCT detected 4 MBs in 3 patients and 21 MBs in 16 patients, respectively (p<0.001). On a per-patient and per-MB basis, significant difference was found between both methods (p=0.001, p<0.001). The 4-D reconstruction showed the milking effect and abnormal blood flow, detecting more MBs than did CAG (p<0.001). The rate of stenosis of the tunneled artery was related to the milking effect on the 4-D reconstruction (r=0.640, p=0.006). Conclusions In the present study, DSCT detected more MBs than CAG, suggesting its clinical application for diagnosis of this condition. (Circ J 2008; 72: 1079 - 1085)

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Background The feasibility of using cardiac multidetector-row computed tomography (MDCT) technology in the quantitative assessment of myocardial blood flow (MBF) using the adenosine triphosphate (ATP) load technique was investigated in the present study. Methods and Results The study group comprised 14 patients (11 men, 3 women, age range 52-79 years, mean age 69.2 years) who underwent cardiac cine MDCT using the ATP-load technique. MBF was estimated from the slope of the linear regression equation with Patlak plots analysis. The overall average MBF was 1.83±0.62 ml · g^-1 · min^-1. Mean MBF in territories with stenosis on coronary angiography was 1.19±0.36 ml · g^-1 · min^-1 and 2.06±0.54 ml · g^-1 · min^-1 (p<0.01) in territories without stenosis. The average MBF in territories with moderate to severe ischemia on myocardial perfusion scintigraphy was 1.32±0.14 ml ·g^-1 · min^-1 and 1.95±0.64 ml · g^-1 · min^-1 (p<0.01) in territories without ischemia. Conclusion MDCT can be used to quantify MBF using first-pass dynamic data. (Circ J 2008; 72: 1086 - 1091)

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Background Because many acute cerebral ischemic events are caused by rupture of vulnerable carotid atheroma and subsequent thrombosis, the present study used both idealized and patient-specific carotid atheromatous plaque models to evaluate the effect of structural determinants on stress distributions within plaque. Methods and Results Using a finite element method, structural analysis was performed using models derived from in vivo high-resolution magnetic resonance imaging (MRI) of carotid atheroma in 40 non-consecutive patients (20 symptomatic, 20 asymptomatic). Plaque components were modeled as hyper-elastic materials. The effects of varying fibrous cap thickness, lipid core size and lumen curvature on plaque stress distributions were examined. Lumen curvature and fibrous cap thickness were found to be major determinants of plaque stress. The size of the lipid core did not alter plaque stress significantly when the fibrous cap was relatively thick. The correlation between plaque stress and lumen curvature was significant for both symptomatic (p=0.01; correlation coefficient: 0.689) and asymptomatic patients (p=0.01; correlation coefficient: 0.862). Lumen curvature in plaques of symptomatic patients was significantly larger than those of asymptomatic patients (1.50±1.0 mm^-1 vs 1.25±0.75 mm^-1; p=0.01). Conclusion Specific plaque morphology (large lumen curvature and thin fibrous cap) is closely related to plaque vulnerability. Structural analysis using high-resolution MRI of carotid atheroma may help in detecting vulnerable atheromatous plaque and aid the risk stratification of patients with carotid disease. (Circ J 2008; 72: 1092-1099)

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Background Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) is associated with a poor prognosis in patients with heart failure (HF). However, some patients do not respond to continuous positive airway pressure (CPAP), so other therapeutic modalities should be considered, such as bi-level positive airway pressure (PAP), which also assists respiration and might be effective for such patients. Methods and Results The 20 patients with HF because of left ventricular systolic dysfunction were assessed: 8 had ischemic etiology, and all had severe CSA according to the apnea - hypopnea index (AHI) determined by polysomnography. All diagnosed patients underwent repeat polysomnography using CPAP. The AHI improved significantly in 11 (AHI <15), but only slightly in 9, in whom the AHI remained high (≥15). Bi-level PAP titration significantly improved the AHI in the latter group. Those who were unresponsive to CPAP had significantly lower PaCO₂, higher plasma brain natriuretic peptide (BNP), longer mean duration of CSR and fewer obstructive episodes than CPAP responders. After 6 months of positive airway support with either CPAP (n=9) or bi-level PAP (n=7), BNP levels significantly decreased and left ventricular ejection fraction significantly increased. Conclusions Bi-level PAP could be an effective alternative for patients with HF and pure CSR-CSA who are unresponsive to CPAP. (Circ J 2008; 72: 1100 - 1105)

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Background For assessment of cardiac sympathetic nervous activity, the conventional protocol for iodine-123-metaiodobenzylguanidine (¹²³I-MIBG) imaging requires several hours. Methods and Results To establish whether it is possible to shorten the conventional ¹²³I-MIBG imaging protocol, anterior planar imaging was performed in 42 heart failure (HF) patients at 5, 15 and 180 min. The washout rate of ¹²³I-MIBG from 5 to 15 min (WR5-15 min) was calculated as a novel index. WR5-15 min closely correlated with the conventional washout rate and inversely correlated with the heart to mediastinum ratio. Univariate Cox analysis revealed that rapid WR5-15 min, augmented plasma B-type natriuretic peptide level, and decreased left ventricular ejection fraction (LVEF) were predictors for cardiac events. Multivariate analysis showed WR5-15 min and LVEF were independent predictors. The cardiac event rate was markedly higher (73%) in patients when both WR5-15 min and LVEF were abnormal. Conclusions WR5-15 min obtained from anterior planar imaging is useful for evaluating the severity of HF and clinical outcome, and may shorten the cardiac ¹²³I-MIBG scintigraphy protocol. (Circ J 2008; 72: 1106 - 1111)

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Background In routine substrate mapping of the left ventricle, an abnormal area is defined as having an amplitude <1.5 mV. However, that is usually too large for catheter ablation in post-infarction ventricular tachycardia (VT) and the use of strict voltage criteria may produce better outcomes. Methods and Results Twenty patients with post-infarction VT underwent substrate mapping using an electroanatomic mapping system. Strict voltage criteria were defined as: non-arrhythmogenic area, >0.6 mV; low-voltage area (LVA), >0.1 to ≤0.6 mV; scar, ≤0.1 mV. Radiofrequency applications targeted the LVA only, which was 48±26 cm², 55% smaller than that of the generally targeted area with an amplitude ≤1.5 mV. The prevalence of delayed electrograms (duration ≥150 ms) was significantly higher in the LVAs than in the border areas with an amplitude of >0.6 to ≤1.5 mV (33.2% vs 3.7%, p<0.001). With the exception of 2 instances of peri-mitral VT, all VT isthmuses resided within the LVA. During follow-up of 24±13 months, 16 patients (80%) have been free of any VT episodes. Conclusions Catheter ablation targeting LVAs with an amplitude ≤0.6 mV appears to be useful for efficient and effective treatment of post-infarction VT. (Circ J 2008; 72: 1112 - 1119)

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Background Atrial fibrillation (AF) characterized by atrial remodeling occurs with obesity-related conditions. Adiponectin, an adipose tissue-derived hormone exerts beneficial effects on ventricular remodeling, so in the present study the potential association between circulating adiponectin levels and atrial remodeling in patients with AF was investigated. Methods and Results The levels of plasma adiponectin, serum carboxy-terminal telopeptide of collagen type I (CITP), as a collagen type I degradation marker, and serum type III procollagen-N-peptide (PIIINP), as a collagen type III synthesis marker, were measured in 304 consecutive patients (162 paroxysmal AF, 46 persistent AF, 96 paroxysmal supra-ventricular tachycardia [controls]). Plasma adiponectin levels were significantly higher in patients with persistent AF than in those with paroxysmal AF or the control patients (p<0.05). Serum CITP levels, but not serum PIIINP levels, were higher in patients with persistent AF compared with the paroxysmal AF and control patients (p<0.05). In addition, there was a positive correlation between adiponectin levels and CITP levels in patients with persistent AF (r=0.39, p<0.005). Conclusions High plasma adiponectin levels are associated with the presence of persistent AF, which is accompanied by increased CITP levels. Thus, measurement of plasma adiponectin could be useful for assessment of AF. (Circ J 2008; 72: 1120 - 1124)

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Background Radiofrequency catheter ablation (RFCA) for curing atrial fibrillation (AF) is often followed by early recurrence and delayed cure, so the present study investigate the predictive factors this in patients with chronic AF. Methods and Results Ninety-two consecutive patients (70 males; mean age, 58.7±6.4 years) with chronic AF who underwent RFCA for treatment of symptomatic AF were enrolled. Early recurrence of AF (ERAF) occurred in 45 patients after ablation. Not achieving AF termination could predict ERAF (odds ratio (OR) 0.95; 95% confidence interval (CI) 0.84-1.13; p=0.02) in multivariate analysis. During a follow-up of 12±11 (range, 5-25) months, delayed cure occurred in 35.6% (16/45) of the patients with ERAF. Left atrial size and AF termination during ablation were related to delayed cure. AF termination was the only independent predictive factor for delayed cure (OR 1.47; 95% CI 1.05-1.87; p=0.02). Conclusion Not achieving AF termination is the only independent predictor of ERAF. Among patients with ERAF, those with a smaller left atrium and AF termination have a higher probability of delayed cure. AF termination can independently predict delayed cure. These results emphasize the importance of AF termination during ablation for patients with chronic AF. (Circ J 2008; 72: 1125 - 1129)

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Background Patients after atrial switch operation for transposition of the great arteries have limited exercise performance. Rigid atrial baffles may cause a relative preload reduction. Previous studies have had suboptimal control groups, which ideally should consist of patients with congenitally corrected transposition of the great arteries (ccTGA) without previous heart surgery, having a systemic right ventricle, but lacking rigid atrial baffles. Therefore the aim of this study was to test the impact of atrial baffles by comparing 12 atrial switch patients with 11 ccTGA patients. Methods and Results Systemic right ventricular stroke volume (SV), heart rate, cardiac index, and other parameters were assessed during rest and dobutamine stress magnetic resonance imaging. The most important difference between the groups was that the atrial switch patients could not increase SV during stress, whereas ccTGA patients increased it significantly. There was no difference between groups in the rise of the cardiac index. Heart rate increased significantly more in atrial switch patients than in ccTGA patients. Conclusions The results support the hypothesis that atrial baffles restrict a rise in SV under dobutamine stress in patients after atrial switch operation for transposition of the great arteries. (Circ J 2008; 72: 1130 - 1135)

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Background Dilatation of the bronchial arteries is a well-recognized feature in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The purpose of the current study was to use computed tomography (CT) to assess the relationship between dilated bronchial arteries and the extent of thrombi, and to evaluate the predictive value of the former for surgical outcome. Methods and Results Fifty-nine patients with CTEPH and 16 with pulmonary arterial hypertension (PAH) were retrospectively evaluated. The total cross-sectional area of bronchial arteries was measured by CT and its relationship with the central extent of thrombi or surgical outcome was assessed. The total area of the bronchial arteries in CTEPH patients was significantly larger than that in PAH patients (median [range], 6.9 [1.7-29.5] mm² vs 3.2 [0.8-9.4] mm²), with the total area of bronchial arteries correlating with the central extent of thrombi. In patients who had undergone pulmonary thromboendarterectomy (PTE) (n=22), the change in PaO₂ after surgery had a tendency to correlate with the total area of the bronchial arteries. Conclusion The total cross-sectional area of the bronchial arteries correlated with the extent of central disease in patients with CTEPH, and it might predict gas exchange improvement after PTE. (Circ J 2008; 72: 1136 - 1141)

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Background Combination therapy has been proposed in treatment algorithms for idiopathic pulmonary arterial hypertension (IPAH), so the additional effects of bosentan in IPAH patients already treated with high-dose epoprostenol (EPO) was evaluated in the present study. Methods and Results Bosentan (62.5 mg twice daily) was administered to 8 IPAH patients already being treated with high-dose EPO (average dose 99.6±43.4 ng · kg^-1 · min^-1). Hemodynamics were assessed at baseline and at 2 days and then 1 year after the initiation of bosentan. Because a remarkable elevation of mixed venous oxygen saturation was observed at the initiation of bosentan, the dosage of EPO was reduced in 7 patients (from 99.6±43.4 to 82.8±31.3 ng · kg^-1 · min^-1, p<0.05). There was a significant decrease from the baseline value for systolic pulmonary artery pressure (80.1±19.3 to 66.8±16.5 mmHg, p<0.05). These effects were maintained for 1 year without progression of PAH in 6 patients whose condition had been stabilized at baseline. Conclusions The additional use of bosentan for IPAH patients whose condition has been stabilized by high-dose EPO is safe and effective. (Circ J 2008; 72: 1142 - 1146)

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Background The pulmonary vascular changes induced by epoprostenol in patients with idiopathic pulmonary artery hypertension (IPAH) have not been reported by a clinical study. Methods and Results Analysis 1 compared the wedged pulmonary angiography (PAG) findings prior to initiation of epoprostenol therapy (n=24) with those after initiation (n=16). Analysis 2 compared the PAG findings prior to and after initiation of epoprostenol therapy (n=9) in the same pulmonary arteries in the same subjects. In analysis 1, a "cotton grass-like" stain originating from the peripheral pulmonary vessels (each vessel could not be distinguished on angiography) was not observable in any of 24 cases before initiation of epoprostenol therapy, but was visible in 13 of 16 cases after (p<0.0001). In analysis 2, the diameter of subsegmental arteries changed from 3.0±0.9 mm (mean ± standard deviation) to 3.7±1.2 mm (p=0.004) between the 2 time periods. Cotton grass-like stain was not found in any cases before epoprostenol, but in all 9 cases after chronic use (p=0.004). Conclusions After initiating epoprostenol therapy, cotton grass-like stain appeared in most patients with IPAH. The possible reason for this is release of severe vasoconstriction and/or emergence of neovascularization. (Circ J 2008; 72: 1147 - 1151)

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Background Patients with congestive heart failure (CHF) are often re-hospitalized, worsening both their quality of life and prognosis. Although renal dysfunction reportedly increases the risk of CHF, the association between renal dysfunction and re-hospitalization for CHF remains unclear. Methods and Results Patients with CHF and decreased renal function were reviewed. The estimated glomerular filtration rate (GFR) was calculated with the Modification of Diet in Renal Disease equation. Patients with decreased renal function (estimated GFR on admission <45 ml ·min^-1 · 1.73 m^-2) were re-hospitalized more frequently than were patients with preserved renal function (estimated GFR on admission ≥45). Patients with decreased renal function were older and had higher rates of anemia, worsening renal function during hospitalization, and previous hospitalization for CHF. Independent predictors of re-hospitalization for CHF identified with multivariate analysis were age, previous hospitalization for CHF, decreased renal function, and non-use of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker. Conclusions Renal dysfunction is an independent predictor of re-hospitalization for CHF, so careful follow-up is needed, even after discharge. (Circ J 2008; 72: 1152 - 1157)

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Background Polymorphisms of the upstream transcription factor 1 (USF1) have been associated with familial combined hyperlipidemia and coronary heart disease. The impact of this gene on subclinical atherosclerosis is unknown. Associations of 3 allelic variants of the USF1 gene and their haplotypes with carotid artery intima - media thickness (IMT), carotid artery compliance (CAC) and brachial artery flow mediated dilatation (FMD) were studied in a population of Finnish healthy young adults. Methods and Results The study population comprised 2,281 individuals participating in the Cardiovascular Risk in Young Finns study. IMT, CAC and FMD values were measured by ultrasound examination. Genotypes were analysed using the 5' nuclease assay. A significant difference in IMT was found for usf1s1 (rs3737787) and usf1s8 (rs2516838) genotypes (p-values 0.046 and 0.021, respectively). Moreover, there was a significant difference between groups in haplotype 1 and haplotype 2 for IMT (p-values 0.011 and 0.028 respectively). In multivariate stepwise linear regression models adjusted by age, sex, body mass index, systolic and diastolic blood pressures, smoking, C-reactive protein, glucose, high- and low-density lipoprotein-cholesterols and triglycerides there were significant associations for the usf1s1 minor genotype AA to predict low IMT (p=0.038) and usf1s8 minor genotype GG to predict high IMT (p=0.003). There was also a significant association for haplotype 2 to predict low IMT in the otherwise similar multivariate model (p=0.006). No associations were found for polymorphisms and CAC, FMD or serum lipids. Conclusions The rs2516838 and rs3737787 polymorphisms of USF1 influence the carotid artery IMT, which is a new finding. (Circ J 2008; 72: 1158 -1164)

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Background Coexisting polymorphisms of the genes affecting clopiogrel resistance may influence platelet activation. Methods and Results In 105 patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention, platelet function was measured and registered as closure time in the test with collagen and adenosine diphosphate (CADP-CT). Patients were followed for 12 months for death or recurrent myocardial infarction (MI). Genotyping revealed 7 carriers of both the C allele of P2Y12 and A allele of CYP2C19 (group 1), 14 carriers of the T allele of P2Y12 and A allele of CYP2C19 (group 2), 17 carriers of the C allele of P2Y12 and G allele of CYP2C19 (group 3) and 67 carriers of the T allele of P2Y12 and G allele of CYP2C19 (controls). The median CADP-CT value was significantly lower in group 1 than in group 2 or 3 (p<0.01) or controls (p<0.002), but did not differ between group 2 or 3 and controls. There were 2 cardiovascular deaths and 4 MI during follow-up, and the median CADP-CT value was lower in these patients (p=0.09). Conclusions Coexisting, rather then single, polymorphisms of different genes may be related to persistent platelet activation while on clopidogrel, which raises concern about harm in patients with ACS. (Circ J 2008; 72: 1165 - 1169)

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Background Previous studies have reported elevated levels of C-reactive protein (CRP) in obese and diabetic subjects, but it is unclear whether both these conditions have an additive effect on the variability of serum CRP levels. Methods and Results The study enrolled 385 men and women who were classified into 4 groups: (1) diabetes (n=97), (2) obesity (n=108), (3) diabetes/obesity (n=78), and (4) healthy (n=102). All were Mexican subjects from Guerrero State. Serum high-sensitivity CRP (hs-CRP) levels were higher in both type 2 diabetes mellitus (T2DM)/obesity and obesity (5.1 mg/L) groups than in the diabetics (1.8 mg/L) without obesity. Only the measurements of obesity were strongly related to hs-CRP (body mass index, r=0.46 and waist circumference, r=0.41). The presence of T2DM and obesity explain 20% of the circulating hs-CRP level, following waist circumference (16%), leukocyte count (10%), diastolic blood pressure (6%), and female gender (4%). Obese subjects (odds ratio (OR)=6.3) and T2DM/obesity patients (OR=6.9) showed high risk for coronary disease and this effect was increased in T2DM/obesity women (OR=9.9). Also, abdominal obesity was associated with high coronary disease risk (OR=5.4), showing an increase in women (OR=7.3). Conclusion High hs-CRP levels are related to obesity and central distribution of body fat, leading to a higher cardiovascular risk among Mexican subjects. (Circ J 2008; 72: 1170 - 1174)

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Background The use of deep hypothermic circulatory arrest (CA) during resection of renal tumors with caval extension is limited in many institutes because of possible adverse effects on immune or platelet function. The present study examined whether routine use of CA implied a negative impact on prognosis. Methods and Results Thirty-six cases of renal tumor with caval extension were retrospectively reviewed (age range, 40-82 years; follow-up, 5 months to 23 years). The mean extension level (Novick classification) in the single clamp (SC) group (n=13), partial bypass (PB) group (n=8), and CA group (n=15) was 1.4, 1.8, and 3.0, respectively. There was 1 operative death (intraoperative pulmonary embolism: PB group) and 1 hospital death (pulmonary embolism of residual tumor: SC group). Volumes of bleeding and transfusion were comparable in the PB and CA groups. Although the level of tumor extension was significantly higher and operation time significantly longer in the CA group than in the other 2 groups (p<0.0001 and p=0.0003), the rate of local recurrence and 5-year survival were comparable among the 3 groups (overall 5-year survival rate 53.1%). Conclusions The benefits and safety of tumor resection under CA might exceed its disadvantages. (Circ J 2008; 72: 1175 - 1177)

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Background Coronary ischemia-reperfusion (I/R) injury causes cardiomyocyte necrosis in a multi-step process that includes an inflammatory reaction. A recent study has suggested that high-mobility group box 1 (HMGB1) is a late mediator of lethal sepsis and an early mediator of inflammation and necrosis following I/R injury. In the present study a neutralizing monoclonal antibody (mAb) for HMGB1 was used to clarify the role of HMGB1 in cardiac I/R injury. Methods and Results Rats underwent 30 min of left coronary artery occlusion followed by 60 min reperfusion. An intravenous injection of anti-HMGB1 mAb or control IgG was administered just before reperfusion. The infarct size was enlarged in the anti-HMGB1 mAb group in comparison with the control group (p<0.05). The treatment of anti-HMGB1 mAb significantly increased the plasma troponin-T and norepinephrine (NE) content in the heart in comparison with the control (p<0.05). Moreover, the production of dihydroxyphenylglycol was reduced in the anti-HMGB1-treated group (p<0.05). Conclusion This study shows for the first time the effects of treatment with neutralizing anti-HMGB1 mAb on I/R injury in the rat heart. The findings support the novel view that I/R-induced HMGB1 may be an important factor in the modulation of interstitial NE. (Circ J 2008; 72: 1178 - 1184)

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Background Radiofrequency catheter ablation (RFCA) targeting the left ventricular posteroseptum (LVPS) and posterior papillary muscle (PPM) terminates or prevents ventricular fibrillation (VF) in rabbit and dog hearts. However, whether the mechanism of VF maintenance is reentry or focal Purkinje firing is unclear. Methods and Results In the present study the effects of RFCA (endocardial ablation of PPM+LVPS in 7 dogs and 7 swine), left ventricular anterolateral wall ablation (LVAL in 7 dogs), and the cut-and-sew operation (CSO: along the left ventricular posterior wall (LVPW) beside PPM in 7 swine) on VF inducibility were compared. (1) VF inducibility was decreased from 100±0% to 21.9±31.2% (p<0.0001) by PPM+LVPS endocardial ablation, but not by LVAL ablation in dogs. (2) LVPW CSO reduced VF inducibility (100±0% to 43.6±9.5%, p<0.0001) in swine. (3) In contrast to the canine Purkinje network, which is mostly localized to the subendocardium, the swine Purkinje network extends to the subepicardial layer with a higher density (p<0.001). Conclusion Both PPM+LVPS ablation (Purkinje destruction) in dogs and LVPW CSO (blocking reentry) in swine reduce VF inducibility, suggesting that in both species focal firing from the Purkinje network and reentry around the PPM contributes to the maintenance of VF. (Circ J 2008; 72: 1185 - 1192)

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Background Pioglitazone added to successful statin therapy may be beneficial for coronary artery disease (CAD) patients without diabetes mellitus. Methods and Results Fourteen individuals optimally treated with statin for >6 months were randomized to a pioglitazone or control group. Pioglitazone significantly improved insulin resistance, reduced high-sensitivity C-reactive protein, increased high-molecular-weight adiponectin and high-density lipoprotein cholesterol levels. Ultrasound echogenicity of carotid atheroma assessed by integrated backscatter was significantly increased by pioglitazone and correlated with adiponectin levels. Conclusion Adding pioglitazone to successful statin therapy may be an effective therapeutic strategy for patients with CAD. (Circ J 2008; 72: 1193 - 1197)

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Endovascular procedure is frequently used as an alternative to surgical bypass in aortic atherosclerotic lesions. Two rare cases of chronic mesenteric ischemia treated with a stent implantation are reported. The patients were a 72-year-old woman and a 57-year-old woman. They presented with severe abdominal pain after meals, repeatedly. Angiography revealed severe stenosis and occlusion of the super mesenteric artery (SMA). Endovascular treatment was initially and technically successful in both patients. A Palmaz^® stent was deployed in the ostium lesion of the SMA for both cases. Completion angiography showed successful recanalization of the SMA without any complication and with satisfactory distal flow. The patients' symptoms were alleviated. They remained asymptomatic after stent implantation. Primary stenting may be considered a viable alternative to conventional surgery in carefully selected patients with chronic mesenteric ischemia due to SMA stenosis. (Circ J 2008; 72: 1198 - 1200)

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Previous randomized trials have shown that drug-eluting stents (DES) are superior to bare-metal stents in reducing the need for target lesion revascularization, but safety issues with DES have recently been raised. We report a rare case of very late stent thrombosis 35 months after sirolimus-eluting stent implantation associated with delayed 5-segment stent fractures and peri-stent aneurysm formation. (Circ J 2008; 72: 1201 - 1204)

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A 48-year-old man suffered from acute coronary syndrome in 1978. Coronary angiography was performed at that time and showed 99% stenosis of the right coronary artery, 100% of the left circumflex branch, and 50% of the left ascending artery. He received conservative therapy. Five years later (ie, 1983), coronary angiography showed complete occlusions of the 3 major coronary arteries. Rich collateral circulation had developed distal to all 3 major coronary trees. The patient and his family rejected invasive therapies such as coronary-artery bypass graft or percutaneous coronary intervention. Cardiac catheterizations were performed in 1996, 2001, and 2007, but angiographic follow-up studies showed no change in either the coronary atherosclerosis or the collateral circulation. The left ventricular ejection fraction has been maintained at >60%. During the 20-year follow-up, he has had refractory angina, but has not suffered from acute coronary syndrome, congestive heart failure, or critical arrhythmia. (Circ J 2008; 72: 1205 -1209)

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Mad-honey disease or honey intoxication is caused by consuming honey produced from leaves and flowers of the Rhododendron family. Here a case of honey intoxication with cardiac involvement is reported. (Circ J 2008; 72: 1210 - 1211)

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The authors apologize for our blunder that we mistake the word `day 26' for `day 7' in Fig 2 and the text. (Circ J 2008; 72: 850-852)

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