Background There have been few large-scale nationwide studies investigating both the prognosis and the prognostic factors of idiopathic dilated cardiomyopathy (IDC). A predictive score that can be used in clinical practice has not been established. Methods and Results A nationwide epidemiological study of the prognosis of IDC was conducted in 1999 among randomly selected hospitals in Japan, and 147 departments participated in the present 5-year follow-up survey. The vital status of 1,554 IDC patients was collected in 2004 using medical records and residence-based registers. The crude 5-year survival rate for those diagnosed in 1998 was 78.6%. Cox's regression model selected 5 independent predictors of mortality: male sex, higher age, higher New York Heart Association functional class, higher left ventricular diameter index, and lower left ventricular ejection fraction. A predictive score using these 5 variables effectively predicted prognosis; 5-year survival rates were 90.6% in patients with a score of 4 or less and 49.0% in patients with a score of 9 or 10. Conclusions This nationwide survey revealed the present prognostic status of IDC in Japan and 5 independent predictors of prognosis that can be used in clinical practice as a predictive score. (Circ J 2008; 72: 343 - 348)

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Background Heart failure (HF), which can be caused by left ventricular systolic dysfunction (LVSD), is a growing problem in developed countries with a large aging population. The aim of the present study was to characterize outpatients with LVSD in the adult population (45-84 years) in an urban Japanese community (Niigata City), and delineate their characteristics in comparison with those in a rural one (Sado). Methods and Results Over a 5-year period, 1,297 patients (67% males) with LVSD (defined as ejection fraction ≤50%) were extracted from 87,953 echocardiography records available in 15 hospitals in Niigata City. The proportion of LVSD increased progressively with age (p-for-trend <0.0001), reaching 1-2% in those aged ≥75 years. The prevalence of comorbidities was noticeable (47% had hypertension, 41% myocardial ischemia, 34% atrial fibrillation, 33% previous hospitalization because of congestive HF, 27% cerebral stroke). In comparison with Sado, Niigata patients were younger, with a higher prevalence of comorbidities (hypertension, diabetes, dyslipidemia, and cerebral stroke). Conclusions As the proportion of LVSD cases increases progressively with age, it is expected to simulate a future epidemic. The differences between patients' characteristics and disease patterns in urban and rural communities may favor individually tailoring preventive strategies for HF in these areas. (Circ J 2008; 72: 349 - 357)

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Background The slope of the relationship between ventilation and carbon dioxide production (VE/VCO₂ slope), obtained during symptom-limited ramp exercise testing, reflects exercise ventilatory efficiency. Importantly, the VE/VCO₂ slope is related to prognosis in patients with congestive heart failure (CHF). The aim of the present study was to determine the relationship between the institution of β-blockers, carvedilol or metoprolol, and the VE/VCO₂ slope during exercise in patients with CHF. Methods and Results Fifty-seven patients with New York Heart Association functional class II or III with a radionuclide left ventricular ejection fraction (LVEF) of less than 40% received carvedilol or metoprolol in a randomized fashion. The VE/VCO₂ slope, LVEF and plasma brain natriuretic peptide (BNP) concentration were determined before and after 16 weeks of treatment. LVEF improved (p<0.01), but the VE/VCO₂ slope and BNP did not. A significant improvement in the VE/VCO₂ slope was observed in patients with LVEF <29% or BNP >63 pg/ml (respective baseline median values) (p<0.05, p<0.05). In patients with BNP >63 pg/ml, the improvement effect on the VE/VCO₂ slope with carvedilol was significantly greater than that with metoprolol (p<0.05) and a significant improvement in the VE/VCO₂ slope was observed only in those who took carvedilol (p<0.01). Conclusions The VE/VCO₂ slope was not improved after β-blocker therapy in any of the patients. However, it did improve in patients with a lower LVEF or higher BNP level at baseline, and carvedilol was more effective than metoprolol in improving the VE/VCO₂ slope in patients with higher BNP levels at baseline. (Circ J 2008; 72: 358 - 363)

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Background The aim of this study was to analyze the relationship between abnormal liver function tests (LFTs) coincident with heart failure (HF) exacerbation and subsequent long-term outcome in patients with chronic HF. Methods and Results The study population consisted of 183 consecutive patients admitted for HF exacerbation with left ventricular ejection fraction ≤40%. Cox proportional hazard analysis revealed that serum total bilirubin (T-Bil) levels on admission (hazard ratio 1.896, p<0.001, 95% confidence interval 1.323-2.717), but not T-Bil at discharge or other LFTs, was an independent predictor of subsequent cardiac events after hospital discharge (cardiac death or readmission for HF exacerbation) The cardiac-event-free rates significantly decreased according to increasing tertiles of T-Bil stratified by the level of 0.7 and 1.2 mg/dl (p<0.001). T-Bil on admission had significant correlations with simultaneously-measured central venous pressure (CVP) (r=0.42, p<0.01) and cardiac index (CI) (r=-0.50, p<0.01). The patients demonstrating high CVP together with low CI showed significantly increased T-Bil compared with any other group. Conclusions Increased T-Bil coincident with cardiac decompensation predicts a worse long-term prognosis of CHF, presumably through the potential liability to both congestion and tissue hypoperfusion simultaneously when HF deteriorates. (Circ J 2008; 72: 364 - 369)

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Background A novel program, "cardioGRAF", has been developed to analyze regional left ventricular (LV) systolic/diastolic function and dyssynchrony, so the present study aimed to use it confirm the presence of LV dyssynchrony, and to correlate LV function and dyssynchrony with plasma B-type natriuretic peptide (BNP) levels during the early to advanced stages of heart failure (HF). Methods and Results Fourteen control subjects (G-C) and 50 patients (New York Heart Association functional class I: G-1, 21 patients; class II: G-2, 15 patients; and class III: G-3, 14 patients) were examined by ECG-gated myocardial perfusion single-photon emission computed tomography, using the new index of dyssynchrony, maximal difference (MD), which is the difference between the earliest and latest temporal parameters among 17 segments. First-third filling rate (FR) and the MD of time to peak FR revealing diastolic dyssynchrony were significantly different between G-C subjects and G-1 patients. Ejection fraction, peak ejection rate, peak FR, MD of time to end-systole, and MD of time to peak ejection rate were significantly correlated with plasma BNP levels. Conclusion Diastolic dyssynchrony was demonstrated even in the early stage of HF, but, although not correlated with the plasma BNP level, systolic dyssynchrony might affect it. (Circ J 2008; 72: 370 - 377)

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Background Diastolic dysfunction is common in patients with overt hypertrophic cardiomyopathy (HCM). Steady-state cine magnetic resonance imaging (MRI) enables measurement of the diastolic function of the left ventricle (LV), and late gadolinium enhanced MRI can delineate the presence and extent of fibrosis in HCM. The purpose of this study was to determine the relationship between the extent of myocardial fibrosis demonstrated by late gadolinium-enhanced MRI and diastolic dysfunction. Methods and Results Seventeen patients (13 men, mean age 57.7±9.8 years) with HCM were studied. The severity index of late gadolinium enhancement was determined by scoring the extent of enhanced tissue in 30 myocardial segments. The peak filling rate (PFR), LV ejection fraction and LV mass were determined by cine MRI. Contrast-enhanced MRI demonstrated late gadolinium enhancement in 97 of 510 segments (19%) and 13 of the 17 patients (77%). The severity index of late gadolinium enhancement demonstrated a significant negative correlation with PFR (r=-0.86, p<0.01) and with the LV ejection fraction (r=-0.59, p<0.05). No significant correlation was observed between the severity index of late gadolinium enhancement and LV mass (r=0.23, p=0.30). Conclusion The extent of myocardial fibrosis revealed by late gadolinium-enhanced MRI has a strong relationship to diastolic dysfunction in patients with HCM. (Circ J 2008; 72: 378 - 383)

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Background To investigate the activation patterns and conduction velocity (CV) in the posterolateral right atrial (RA) wall during typical counterclockwise atrial flutter (AFL) using an electroanatomic mapping system. Methods and Results During typical AFL in 25 patients, the transverse conduction pattern and CV were classified and calculated. The line blocking transverse conduction was defined by the conduction pattern and double potentials recorded during mapping. There were 3 types (including 2 subtypes) of transverse conduction pattern based on the conduction blocks across the posterolateral RA in a line between the superior and inferior venae cava. Trans-cristal conduction activation in a horizontal direction was seen in all but 4 patients. The CV in the gap area was 0.59±0.21 m/s. Conclusions Three types of transverse conduction pattern were observed during trans-ctristal conduction and the trans-ctristal CV was relatively slower than that in other parts of the RA, except for the isthmus. (Circ J 2008; 72: 384 - 391)

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Background Percutaneous coronary intervention (PCI) with drug-eluting stents (DES) may be useful in patients with acute myocardial infarction (AMI), but safety issues still need to be solved. This study was undertaken to investigate the incidence of major adverse cardiac events (MACE) and stent thrombosis in DES-implanted AMI patients in real-life clinical practice. Methods and Results On-line registry of AMI cases at the web site www.kamir.or.kr has been performed in 41 primary PCI centers in Korea and between November 2005 and September 2006, 1,541 surviving patients who had been implanted with either Cypher^® or Taxus^® stents were enrolled for analysis during a 6-month clinical follow-up. There were 2 groups: group I [834 patients, 61.9±11.9 years: sirolimus-eluting stent (Cypher^®)], group II [707 patients, 62.9±12.0 years: paclitaxel-eluting stent (Taxus^®)]. At both 1 and 6 months the incidence of MACE was not significantly different between the 2 groups. There were 17 cases of stent thrombosis, but the incidence of stent thrombosis was not significantly different between the 2 groups (group I:II=9 (1.1%):8 (1.1%), p=1.000). The stent type, length, number, lesion complexity and diabetes were not significant for the incidence of MACE or stent thrombosis after adjustment. Conclusion MACE and stent thrombosis rates did not differ between 2 types of DES identified in Korea Acute Myocardial Infarction Registry (KAMIR). DES can be used in patients with AMI with a relatively low 6-month MACE rate. (Circ J 2008; 72: 392 - 398)

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Background Multiple angioscopic yellow plaques are associated with diffuse atherosclerotic plaque, and may be prevalent in patients with myocardial infarction (MI), so in the present study the yellow plaques in the coronary arteries of patients with MI was evaluated using quantitative colorimetry, and compared with those of patients with stable angina (SA). Methods and Results In the recorded angioscopic images of 3 coronary vessels in 29 patients (15 patients with MI, 14 with SA), yellow plaques were determined as visually yellow regions with b* value >0 (yellow color intensity) measured by the quantitative colorimetric method. A total of 90 yellow plaques were identified (b* =19.35±8.3, 3.05-45.35). Yellow plaques were significantly more prevalent in 14 (93%) of 15 culprit lesions of MI as compared with 8 (57%) of 14 of SA (p=0.03). In non-culprit segments, yellow plaques were similarly prevalent in 13 (87%) patients with MI and 11 (79%) with SA (p=0.65). Overall, multiple (≥2) yellow plaques were prevalent in 13 (87%) patients with MI, similar to the 10 (71%) with SA (p=0.38). The number of yellow plaques was significantly higher in patients with MI (3.8±1.9) than in those with SA (2.4±1.6, p=0.03). Conclusion The present study suggests that patients with MI tend to have diffuse atherosclerotic plaque in their coronary arteries. (Circ J 2008; 72: 399 - 403)

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Background Patients with cerebral infarction have a high prevalence of asymptomatic coronary artery disease (CAD) and other vascular diseases, but there is a lack of such data for Japanese patients, so the present study investigated the prevalence of cardiovascular disease (CVD) in Japanese patients and determined the predictors of CAD. Methods and Results The study group comprised 104 patients with cerebral infarction who had no history of CVD. All patients underwent coronary computed tomographic angiography, and systematic evaluation was done on the basis of the presence of other vascular diseases, CVD risk markers, and the degree of atherosclerosis. Of the total, 39 patients (37.5%) had CAD, 9 (8.7%) had carotid artery stenosis, 9 (8.7%) had peripheral artery disease of the lower limbs, and 3 (2.9%) had atherosclerotic renal artery stenosis. Multiple regression analysis showed that the presence of CAD was independently associated with metabolic syndrome (odds ratio (OR) 5.008, 95% confidence interval (CI) 1.538-16.309; p<0.01) and intracranial large artery atherosclerosis (OR 4.979, 95% CI 1.633-15.183; p<0.01). Conclusion Japanese patients with cerebral infarction have a high prevalence of CVD, especially asymptomatic CAD. Both metabolic syndrome and intracranial large artery atherosclerosis may be potential predictors for identifying patients with cerebral infarction who are at the highest risk of asymptomatic CAD. (Circ J 2008; 72: 404 - 408)

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Background In patients with acute myocardial infarction (AMI), the relationship of serial changes in ST-segment elevation after reperfusion to left ventricular (LV) function remains unclear. Methods and Results The study group comprised 164 patients with reperfused anterior AMI within 6 h of symptom onset. The sum of ST-segment deviation was calculated on admission (ΣST-admission), and 1 h (ΣST-1 h) and 24 h (ΣST-24 h) after reperfusion. ST resolution was defined as a reduction in ΣST-1 h of ≥50% as compared with ΣST-admission. Patients were classified into 3 groups: group A, 82 patients with ST resolution in whom ΣST-1 h ≥ ΣST-24 h; group B, 37 patients with ST resolution in whom ΣST-1 h < ΣST-24 h; group C, 45 patients without ST resolution. Peak creatine kinase were higher in groups B and C than in group A (4,578±2,176, 4,236±2,638, 2,222±1,926 mU/ml, p<0.01). At 6 months follow-up, the LV ejection fraction were lower in groups B and C than in group A (53±8, 54±12, 62±9%, p<0.01). Conclusions An increase in ST-segment elevation 1-24 h after reperfusion, despite ST resolution, is associated with a larger infarction and poorer LV function in patients with reperfused anterior AMI. (Circ J 2008; 72: 409 - 414)

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Background Population-based cohort studies demonstrate that metabolic syndrome (MeS) is associated with increased risk for cardiovascular diseases and related mortalities. The present study was designed to investigate the prognostic impact of MeS in patients with acute myocardial infarction (AMI). Methods and Results The study group was 461 AMI patients without a history of previous myocardial infarction. On the basis of the National Cholesterol Education Program Adult Treatment Panel III criteria, MeS was defined having at least 3 of the following 5 conditions: dysglycemia (impaired fasting glucose, current use of insulin or oral hypoglycemic drugs), hypertriglyceridemia, low high-density lipoprotein-cholesterol level, hypertension and obesity. The prevalence of MeS was 37% (n=172). C-reactive protein (CRP) levels increased with the increase in the number of conditions of MeS. During follow-up at a median of 17.6 months, the incidence of major adverse cardiovascular events (MACE) was significantly different between patients with and without MeS. Furthermore, after adjustment of predictive factors (age, sex, Killip class, multivessel coronary artery disease, low ejection fraction and high CRP level), MeS was an independent risk factor for MACE. Conclusions In patients with AMI, MeS is associated with systemic inflammation and is an important predictor for MACE, which suggests the need for early identification and medical intervention for secondary prevention of MeS. (Circ J 2008; 72: 415 - 419)

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Background There are few monitoring systems widely used in clinical practice for evaluating the effectiveness of aspirin therapy, so in the present study aspirin's antiplatelet effects we investigated with a whole blood aggregometer using a screen filtration pressure (SFP) method. Methods and Results Thirty-five healthy male volunteers took 100 mg/day aspirin for 14 days. Whole-blood aggregation was analyzed at baseline and on days 7 and 14, using collagen and adenosine diphosphate as the stimuli, and compared with the platelet-rich plasma (PRP) aggregation measured by optical aggregometer. The platelet-aggregation threshold index (PATI) for both methods, which was defined as the putative agonist-concentration giving half-maximal aggregation, and the PRP-maximal aggregation rate were analyzed. The maximal aggregation rate induced by 1.6 mg/L collagen decreased from 85.5% (80.8-92.8) [median (interquartile range)] at baseline to 51.5% (39-63.8) on day 14 (p<0.0001). The PRP-PATI and whole-blood PATI for collagen increased from 0.32 (0.28-0.70) to 1.82 mg/L (1.25-2.89) (p<0.0001) and from 0.28 (0.22-0.3) to 1.06 mg/L (1.01-1.29) (p<0.0001) respectively. Conclusions The whole-blood PATI and PRP-PATI for collagen, as well as the maximal PRP aggregation rate, clearly distinguish platelet aggregability before and after aspirin intake. However, whole-blood analysis by the SFP-method is easier to perform, and is a promising method of monitoring aspirin's effects. (Circ J 2008; 72: 420 - 426)

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Background There have been few studies regarding the effect of contrast agent on long-term renal function and, moreover, there are still many uncertainties regarding the efficacy of prophylactic hemodiafiltration (HDF) for contrast-induced nephropathy. Methods and Results Patients with heart disease and a serum creatinine level (Scr) of less than 1.2 mg/dl were classified as Group N (20 patients), those with Scr of at least 1.2 mg/dl but less than 2.0 mg/dl were classified as Group D1 (10 patients without HDF) and D2 (15 patients with HDF), respectively. For each group, a linear regression of 1/Scr was extrapolated using Scr measured more than 3 times during each period that was longer than 3 months before and after use of a contrast agent, and the slopes (constant k) thereof were compared. To remove the contrast agent, HDF was performed for 2 h. Group D1 showed a significant decrease in the k after use of the contrast agent (p<0.05). Conclusion Use of a contrast agent is an independent factor that promotes chronic renal insufficiency and prophylactic HDF was found to effectively improve the long-term outcome of decreased renal function. (Circ J 2008; 72: 427 - 433)

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Background The cut-and-sew Maze procedure has historically been the most efficacious therapy for patients with atrial fibrillation (AF) that is refractory to medical management, but is not widely used as a stand-alone treatment for AF. New ablation technologies can create pulmonary vein (PV) isolation without cardiopulmonary bypass. Methods and Results The `thoracoscopic mini-Maze' procedure includes bilateral PV isolation, ablation of the epicardial ganglionated plexi and excision of the left atrial appendage using small bilateral thoracotomies with thoracoscopic assistance. Between January 2006 and April 2007, 20 thoracoscopic mini-Maze procedures were performed at 2 institutions and over a mean follow-up of 16.6 months, 18 (90%) patients are in sinus rhythm. Perioperative bleeding complications occurred in 3 patients (15%) and there was 1e (5%) late instance of atrial flutter that required a right-sided ablation. None of the patients died or needed a pacemaker. Conclusions Early experience with the thoracoscopic mini-Maze procedure suggests that sinus rhythm can be re-established in most patients in the short-term and with more experience the rate of complications should reduce, which is required prior to defining the role of this therapy in the future treatment of AF. (Circ J 2008; 72: 434 - 436)

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Background Few studies have used the cumulative sum method to examine the initial performance of a newly appointed cardiac surgery team at a low-volume hospital. Methods and Results In the 4 years from April 2002 to December 2006, 274 cases of open-heart surgery were performed and the overall mortality and morbidity rates were 4.01% and 5.84%, respectively. The respective rates for coronary, valvular and aortic surgery were 2.05% and 2.74%, 3.61% and 7.23%, and 11.1% and 13.3%. The overall cumulative sum curve was below the 80% upper alarm line since the 58^th case and below the 80% lower alarm line since the 139^th case. The respective values for the cumulative sum curves of valvular and coronary surgery were the 1^st and 41^st cases, the 22^nd and the 76^th cases, but for aortic surgery the cumulative sum curve remained below the 80% upper alarm line since the 1^st case but did not reach below the 80% lower alarm line Conclusions An open-heart surgery unit at a low-volume hospital could compete with a high-volume hospital if it has a safe launching and low mortality and morbidity rates. The predictor of a safe launching is not the annual volume, but the cumulative experience of the surgical team. (Circ J 2008; 72: 437 - 440)

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Background The primary objective of the present study was to determine whether there is an association between the ankle - brachial index (ABI) and the risk factor profile in patients with newly diagnosed peripheral arterial disease (PAD). A secondary objective was to identify the risk factor profile of these patients, and evaluate how well these factors are controlled in the primary care setting. Methods and Results In this cross-sectional study, all new consecutive patients referred by primary care to a vascular surgery outpatient clinic, after diagnosis of PAD was confirmed, were subsequently referred to the Risk Factor Modification Clinic for assessment and management of their risk factors. Patients with intermittent claudication (n=170) (age 68.7±10.6 years; 118 men; ABI 0.65±0.13) were included. In patients not on lipid-lowering drugs, low-density lipoprotein-cholesterol (LDL-C) was inversely correlated with the ABI (r=-0.42, p<0.0001). Also ABI was significantly correlated with serum creatinine (r_s=-0.38, p<0.0001) (and estimated glomerular filtration rate), high-sensitivity C-reactive protein (hsCRP) (r_s=-0.20, p=0.009) and plasma fibrinogen (r_s=-0.18, p=0.018). In stepwise multiple linear regression analysis, hsCRP and creatinine levels and diabetes were independent predictors of ABI (p<0.0001). Only 32.4% of the patients had normal blood pressure and 25.9% had an optimal LDL-C level <2.6 mmol/L (100 mg/dl); 85.3% were ever smokers; 44.1% had diabetes/impaired fasting glucose; 84.7% had hsCRP >3.0 mg/L; 78.8% fibrinogen >3.0 g/L (300 mg/dl); and 68.8% homocysteine >12.0 μmol/L (44.7% >15.0 μmol/L). Conclusions For the first time, a significant inverse correlation between ABI and LDL-C was shown in patients not on lipid-lowering drugs, and also between ABI and creatinine, hsCRP and fibrinogen in all patients, supporting a link between the severity of PAD and atherogenic and inflammatory risk factors. HsCRP, creatinine and diabetes were independently associated with the ABI. Despite the increased vascular risk, PAD remains undertreated in the primary care setting. Increased awareness will overcome this barrier to effective secondary prevention of vascular events. (Circ J 2008; 72: 441 - 448)

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Background Although the left subclavian artery (LSA) is simply covered to exclude distal aortic arch aneurysm during endovascular stent-grafting, this technique is potentially harmful. Methods and Results Between January 2001 and April 2005, 40 cases of stent-grafting were performed for distal aortic arch diseases. For all 31 elective cases, the LSA occlusion test using a balloon catheter was preoperatively performed to predict critical complications secondary to LSA coverage by a stent graft and this revealed 2 cases in which the LSA was crucial for brain circulation (6.5%). The LSA was saved by using a hand-made fenestrated stent graft without bypass-grafting to the LSA in 22 cases. Bypass-grafting to LSA was performed in 5 cases. The LSA was simply occluded in 13 cases. Hospital mortality rates for the elective and emergency cases were 3.2% and 30.0%, respectively. One elective patient had a cerebral infarction (2.5%). LSA patency was successfully maintained in all 22 cases using a fenestrated stent graft. Conclusion The LSA plays an important role in brain circulation in some patients and so a preoperative LSA occlusion test is helpful when aortic stent-grafting is proposed. Fenestrated stent graft saved the LSA in more than 50% of the present cases. (Circ J 2008; 72: 449 - 453)

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Background Increased heart rate (HR) and metabolic syndrome are risk factors for cardiovascular morbidity and mortality, but their relationship has not been studied in a large, screened cohort. Methods and Results The association between HR and multiple risk factor syndrome, resembling metabolic syndrome, was examined in participants of a health evaluation program in 1997. Of the 8,432 subjects (5,223 males, 3,209 females, 18-89 years of age), 1,502 (1,185 males, 317 females) were diagnosed with multiple risk factor syndrome and these subjects had higher HR than those without the syndrome (p<0.0001); subjects with a higher number of risk factors had higher HR than those with fewer risk factors (males, p<0.0001; females, p<0.0001). After adjusting for age, sex, and lifestyle factors, subjects within the highest HR quartile had a 2.5-fold higher risk for multiple risk factor syndrome than those in the lowest quartile (p<0.0001). An increase of 10 beats/min was associated with an approximately 30% increase in the risk for multiple risk factor syndrome. Conclusions A higher HR is closely associated with multiple risk factor syndrome. (Circ J 2008; 72: 454 - 457)

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Background It has been reported that sympathetic nerve activity (SNA) is associated with fibrinolysis, but the interaction between SNA and the fibrinolytic system with aging has not been elucidated in humans. The purpose of this study was to examine the effect of age-related SNA on the activity of plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (tPA) using muscle SNA (MSNA). Methods and Results This study included 16 young subjects (mean age 26.1 years) and 10 aged subjects (mean age 56.9 years). Lower body negative pressure (LBNP) was performed at -40 mmHg for 30 min. LBNP significantly increased both tPA and PAI-1 activity (from 5.2±0.5 to 7.3±1.2 IU/ml and from 2.85±0.68 to 4.06±0.73 U/ml, p<0.01, respectively) in the aged group. In the young group, tPA activity tended to increase, whereas PAI-1 activity was unchanged. There was a correlation between MSNA and PAI-1 activity in the aged group (r=0.47, p<0.01). Conclusions SNA in an aging subject leads to an increase in the activity of PAI-1, which indicates that an altered interaction between SNA and PAI-1 activity contributes to increased cardiovascular events in the elderly population. (Circ J 2008; 72: 458 - 462)

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Background This study evaluated the inflammatory reaction at the site of overlapping drug-eluting stents (DES) in a porcine model of in-stent restenosis. Methods and Results Twenty bare metal stents (BMS) (group I; n=10), 20 sirolimus-eluting stents (SES) (group II: n=10), 20 paclitaxel-eluting stent (PES) (group III: n=10), and 10 PES and 10 SES (group IV: n=10) were overlapped in the left anterior descending coronary arteries of 40 pigs. Follow-up coronary angiography and histopathology were performed at 4 weeks after stenting. For the overlapped segments, the minimal luminal diameter at 4 weeks was smaller in group I than in the other groups (1.78±0.13 mm, 2.79±0.09 mm, 2.90±0.04 mm, 2.80±0.07 mm, respectively; p<0.001), and the neointimal area (5.51±0.58 mm², 2.38±0.53 mm², 2.07±0.37 mm², 2.39±0.58 mm², respectively; p<0.001) and area stenosis (68.74±4.02%, 27.79±4.73%, 23.66±3.24%, 27.63±4.07%, respectively; p<0.001) were higher in group I than in the other groups; however, the inflammatory score was higher in group III than in the other groups (1.80±0.42, 2.10±0.32, 2.90±0.31, 2.50±0.52, respectively; p<0.001) and the endothelization score was lower in group III than in the other groups (2.80±0.42, 2.30±0.67, 1.30±0.48, 2.10±0.74, respectively; p<0.001). Conclusion Compared with BMS, DES inhibit neointimal hyperplasia, but inflammation and poor endothelization occur at the site of overlapping stents. (Circ J 2008; 72: 463 - 468)

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Background Interleukin (IL)-13, which is a cytokine produced by type 2 helper T cells, has pathophysiological roles in allergic inflammation and fibrosis formation. IL-13 shares many functional properties with IL-4, which is known to inhibit angiogenesis. Methods and Results The effects of IL-13 on angiogenesis were examined using human coronary artery endothelial cells (HCAECs), in addition to investigating the mechanism(s) of this action. Using an in vitro assay of angiogenesis it was demonstrated that IL-13, as well as IL-4, significantly inhibited capillary-like tube formation. Migration of HCAECs, considered to be a process of new capillary tube formation, was also significantly inhibited by IL-13. IL-13 activated signal transduction and transcription 6 (STAT6) as a result of the activation of Janus kinase 2 (JAK2). The inhibitory effect of IL-13 on angiogenesis was abolished by depletion of JAK2 and STAT6 by RNA interference. Conclusion IL-13 has anti-angiogenic activity as a result of activation of JAK2 and subsequent activation of STAT6. (Circ J 2008; 72: 469 - 475)

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Background Pulmonary hypertension (PHT) is a common complication of congenital heart disease and the pulmonary vascular structural remodeling because of the high pulmonary blood flow is considered to be the key pathologic process. In the present study the change and distribution of peptides derived from proadrenomedullin in a rat model of PHT caused by a left-to-right shunt were measured to elucidate the mechanism. Methods and Results Twelve weeks after a cervical shunt was established by a cuff technique in an experimental group of rats, the systolic pulmonary artery pressure (sPAP) was measured by catheterization. Morphologic assessment included the measurement of the weight ratio of the right ventricle (RV) to the left ventricle plus septum (LV+SP) and the mean percentage of media wall thickness (MT%) in moderate-sized pulmonary arteries. The distribution of adrenomedullin (ADM), adrenotensin (ADT) and proadrenomedullin N-terminal 20 peptide (PAMP) were measured by immunohistochemical staining. The mRNA expressions of ADM, ADT, PAMP and proADM45-92 were investigated by reverse transcription polymerase chain reaction. The sPAP and the ratios of RV/(LV+SP) and MT% were significantly increased in the experimental rats (p<0.01, and p<0.05). Positive signals (brown granules) of ADM, ADT and PAMP were mainly located in the smooth muscle cells, but the brown granules of PAMP were also located in the tunica adventitia. The levels of ADM and PAMP were significantly increased, while that of ADT was markedly decreased in the Experimental group compared with the Control group (p<0.05 and p<0.01 respectively). The mRNA expression levels of ADM and preADM45-92 were significantly increased in the experimetnal rats (p<0.01); however, the expression of ADT mRNA was statistically deceased in the Experimental group compared with the Control group (p<0.01). The mRNA expression of PAMP showed no statistical difference between the 2 groups of rats (p>0.05). Conclusions The change and distribution of peptides derived from proadrenomedullin in PHT caused by a left-to-right shunt in rats is powerful evidence for intramolecular regulation. (Circ J 2008; 72: 476 - 481)

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Background Alterations in intravascular pressure can affect vascular function and the morphological properties of arteries. Although it has been shown that a transient elevation of blood pressure impairs endothelium-dependent dilation in small arteries, the vascular dilation responses during high intravascular pressure have not yet been investigated. Methods and Results Using pressure myography, the endothelium-dependent and -independent dilation responses of small mesenteric arteries of rats were examined under 3 different intravascular pressure conditions (50, 80 and 120 mmHg). Endothelium-dependent dilation was evaluated by measuring vasodilator responses to increasing doses of acetylcholine (ACh, 10^-9 to 10^-4 mol/L) or increases in intraluminal flow (7-36 μl/min). Endothelium-independent vasodilator function was examined by using sodium nitroprusside (SNP, 10^-9 to 10^-4 mol/L). Flow-mediated dilation was significantly attenuated at 120 mmHg whereas ACh-induced dilation was progressively decreased with increases in intravascular pressure (at 80 and 120 mmHg). Significant attenuation in the vasodilator response to SNP was also observed at 80 and 120 mmHg. Conclusion Endothelium-dependent and-independent dilation responses are progressively attenuated with acute increases in intravascular pressure. (Circ J 2008; 72: 482 - 486)

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Background Before performing cardiac resynchronization therapy (CRT), it is useful to visualize the position of the coronary sinus (CS) orifice where the CS lead is inserted. Methods and Results A raysum image was created in which the outermost 1-voxel layer of the right atrium (RA) and CS was extracted. This image enabled visualization of the positional relationship between the RA and CS ostium using the same geometry as retrograde CS venography. Conclusion New post-processing imaging of the CS orifice will make the procedure of CRT safer. (Circ J 2008; 72: 487 - 488)

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Background The future burden of heart failure in Japan was projected to 2055 in order to prospectively estimate of the number of these patients. Methods and Results The statistics are based on prevalence data of left ventricular dysfunction (LVD) in Sado City using the Sado Heart Failure Study (2003) and population estimates from the Japanese National Institute of Population and Social Security Research Report (2006). The number of Japanese outpatients with LVD was 979,000 in 2005, and is predicted to increase gradually as the population ages, reaching 1.3 million by 2030. Conclusion LVD is expected to precipitate a future epidemic of heart failure in Japan. (Circ J 2008; 72: 489 - 491)

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Berry syndrome is a very rare congenital cardiovascular anomaly that consists of a distal aortopulmonary window, aortic origin of the right pulmonary artery, an intact ventricular septum, a patent ductus arteriosus, and an interrupted aortic arch. Two cases of Berry syndrome are presented. A one-stage surgical correction for this complex anomaly was successfully performed, and a 1-year follow-up demonstrated favorable outcomes. (Circ J 2008; 72: 492 - 495)

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A 12-year-old boy born with double outlet right ventricle (RV) developed sustained ventricular tachycardia (VT) 6 years after the corrective surgery and underwent electrophysiologic testing and catheter ablation. Electroanatomic mapping of the right and left ventricles during the VT revealed a centrifugal activation from the outflow tract septum. Though an excellent pace map was obtained in the RV, successful ablation was achieved on the left side. These findings suggested that the VT origin might have been located in the intramural region of the ventricular outflow tract septum with a preferential breakout site in the RV outflow tract. (Circ J 2008; 72: 496 - 499)

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Human brucellosis is a rare zoonosis in East Asia. A case of brucella endocarditis in a 59-year-old farmer who had mild rheumatic mitral stenosis is presented. Excision of the mitral valve with associated vegetation was performed and a mechanical valve was substituted. Antibiotic treatment with doxycycline, rifampicin, and trimethoprim/sulfamethoxazole was continued for 6 months. After 18 months of follow-up, the patient had no symptoms and no signs of relapse. (Circ J 2008; 72: 500 - 501)

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Two cases of drug-eluting stent restenosis after percutaneous coronary intervention in the left main coronary artery and its bifurcation are presented. An off-pump coronary artery bypass grafting following in-stent restenosis was performed. Drug-eluting stents have shown a reduced frequency of in-stent restenosis and a good safety profile compared with bare metal stents. However, intervention with drug-eluting stents for left main coronary artery disease should be undertaken with care. It is also important to note that preoperative anti-platelet drug administration can increase the risk of major bleeding during and after emergent surgery. (Circ J 2008; 72: 502 - 504)

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The author (N. Komura) apologizes for errors which appeared in the Table 1, page 25, Vol. 72. The numbers and proportion of hypertension or current smokers were 72 (55%), 61 (47%) in non-diabetic patients, and 39 (70%), 26 (46%) in diabetic patients, respectively. The corrected Table 1 is given below. (Circ J 2008; 72: 23 - 28)

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