Background Restenosis still occurs, even with the sirolimus-eluting stent (SES), and the precise mechanisms and the impact of stent fracture on restensosis have not yet been elucidated. Methods and Results Intravascular ultrasound (IVUS)-guided SES implantation was performed in 184 lesions in 151 patients with stable and unstable angina. Serial (pre-, post- and follow-up) quantitative coronary angiography analysis was obtained in 169 lesions in 138 patients (angiographic follow-up rate: 91%) and 12-month clinical follow-up was done in all patients. Restenosis occurred in 13 (7.7%) of 169 lesions. Stent fracture occurred in 4 (2.4%) of 169 lesions at follow-up. Of the 13 restenotic lesions, 8 had intimal hyperplasia, 4 had stent fracture, and 1 had late stent thrombosis at 7 months. Although multivariate logistic regression analysis revealed that minimal lumen area (min-LA) post (p=0.027), total stent length (p=0.003) and diabetes (p=0.032) were significant independent predictors of restenosis, univariate analysis showed that stent fracture was more common in the restenosis than in the non-restenosis groups (p=0.001). Conclusions Although min-LA post by IVUS, total stent length by QCA and diabetes are independent predictors for angiographic restenosis, stent fracture occurred in 4 lesions (2.4%) and all of them resulted in restenosis (31% of the restenosis). The impact of stent fracture and its potential role in the development of restenosis deserves further study. (Circ J 2007; 71: 1669 - 1677)

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Background Recent lipid-lowering trials have reported that statin therapy may retard progression or stimulate regression of human coronary plaque. In the present study volumetric intravascular ultrasound (IVUS) analyses were performed to investigate the effect of pitavastatin, a newly developed statin, on regression of human coronary plaque. Methods and Results Eighty-two patients matched for age and gender from 870 consecutive patients undergoing IVUS guided percutaneous coronary intervention were retrospectively assigned to either lipid-lowering therapy (n=41; pitavastatin 2 mg/day) or control group (n=41; diet only). Serial volumetric IVUS analyses of a matched left main coronary arterial site were performed. A significant reduction in low-density lipoprotein-cholesterol (LDL-C) level of 33.2% (p<0.001) was observed in the pitavastatin group. Plaque volume index (PVI) was significantly reduced in the pitavastatin group (10.6±9.4% decrease) compared with the control group (8.1±14.0% increase, p<0.001). There were positive correlations between the percent change in the PVI and follow-up LDL-C level (r=0.500, p<0.001) and the percent change in LDL-C level (r=0.479, p<0.001). Conclusion Lipid-lowering therapy with pitavastatin induced significant coronary plaque regression, associated with a significant reduction in the LDL-C level. The percent change in the PVI showed a significant positive correlation with the percent change in LDL-C level. (Circ J 2007; 71: 1678 - 1684)

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Background This study was designed to investigate the efficacy of cilostazol on the prevention of in-stent neointimal hyperplasia as measured by both quantitative coronary angiography (CAG) and volumetric intravascular ultrasound (IVUS). Methods and Results Fifty-nine patients (39 men, age 62 years) undergoing elective coronary stenting were randomly assigned to receive aspirin plus clopidogrel or ticlopidine (Group I, n=28, 30 lesions) or aspirin plus clopidogrel or ticlopidine plus cilostazol (Group II, n=31, 35 lesions). CAG and IVUS were performed and repeated at 6 months to assess the primary endpoints of minimal luminal diameter (MLD) and in-stent neointimal hyperplasia volume. Follow-up CAG was performed on all patients and follow-up IVUS study was available for 50 lesions in 48 patients (24 lesions in Group I, 26 in Group II). There were no significant differences in the baseline angiographic data between the 2 groups. At 6 months follow-up, in-stent MLD was 1.90±0.76 mm in Group I and 2.41±0.85 mm in Group II (p=0.006). Volumetric IVUS at 6 months demonstrated that in-stent intimal hyperplasia volume per stent length was 2.2±1.4 mm³/mm in Group I and 1.0±0.5 mm³/mm in Group II (p=0.001). Conclusions Triple antiplatelet therapy including cilostazol seems to be more effective at preventing in-stent neointimal hyperplasia than a dual antiplatelet regimen. (Circ J 2007; 71: 1685 - 1690)

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Background The prognostic value of the level of interleukin (IL)-18 in patients after acute ischemic stroke (IS) has not been completely investigated. This prospective cohort study examined whether the circulating IL-18 level can predict 90-day outcome of IS. Methods and Results Plasma IL-18 level was obtained from blood samples taken by venous access at 48 h following acute IS in 217 consecutive patients. Plasma IL-18 level was also evaluated in 20 healthy and 40 at-risk control subjects. Plasma levels of IL-18 and white blood cell (WBC) counts were significantly higher in IS patients than in both control groups (all p values <0.0001). Patients with high IL-18 level (≥780 pg/ml) had significantly higher incidences of 90-day recurrent stroke and 90-day accumulative death (all p values <0.01). Univariate analysis demonstrated that IL-18 level (≥780 pg/ml), modified Rankin scale score, WBC count, creatinine level, and coronary artery disease were significantly associated with 90-day major adverse clinical outcomes (MACO) (defined as combined 90-day recurrent stroke and 90-day mortality) (all p values <0.05). Multiple stepwise logistic regression analysis demonstrated that high IL-18 level (≥780 pg/ml) (p<0.0001), together with creatinine level (p=0.024), were independently predictive of 90-day MACO. Conclusions Plasma IL-18 level is a major independent inflammatory predictor of 90-day MACO in IS patients. Evaluation of circulating IL-18 level might improve the prediction of unfavorable clinical outcome following IS. (Circ J 2007; 71: 1691 - 1696)

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Background Type 2 diabetes mellitus (T2DM) has been reported as a major risk factor for in-stent restenosis (ISR) after intracoronary stenting, although the details of the mechanisms remain undefined. The aim of present study was to investigate the diabetes-related risk factor for ISR. Methods and Results A total of 131 patients who were implanted with bare metal stent(s) were enrolled in this study. Based on follow-up coronary angiography at 6 months after stenting, the patients were classified according to the presence or absence of ISR. Various coronary risk factors, including serum malondialdehyde-modified low-density lipoprotein (MDA-LDL) levels, were investigated at follow-up angiogram to relate to ISR in patients with or without T2DM. The increased incidence of ISR was observed in diabetic patients, which was significantly related to the increased serum MDA-LDL concentrations. The serum MDA-LDL concentration was positively correlated to glycohemoglobin levels in diabetic patients. In addition, MDA-LDL concentration was not altered after the treatment of ISR. Conclusions The elevated serum MDA-LDL level is considered to be a potent risk factor for ISR in diabetic patients. MDA-LDL, which might be a consequence of metabolic abnormalities caused by diabetes, may act as a growth factor for neointimal tissues inside the implanted stent. (Circ J 2007; 71: 1697 - 1702)

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Background Impaired glucose tolerance (IGT) is a significant risk factor for cardiovascular disease, but is not always recognized in the clinical setting. An anti-atherogenic adipocytokine, adiponectin, is decreased in type 2 diabetes mellitus, but its role in non-diabetic subjects has not been clarified. The hypothesis investigated in the present study was that plasma adiponectin levels correlate with IGT and coronary artery disease (CAD) in non-diabetic men. Methods and Results Glucose intolerance was evaluated by an oral glucose tolerance test and plasma adiponectin levels were measured in 232 non-diabetic men who underwent coronary angiography. Patients with IGT (n=102) had significantly lower adiponectin levels than those with normal glucose tolerance (n=130) (4.47 [3.23-6.39] vs 5.85 [3.99-8.65] μg/ml, p=0.003). Plasma adiponectin levels were associated with IGT in multiple logistic regression analysis (odds ratio (OR) 0.623, 95% confidence interval (CI) 0.397-0.980; p=0.041). Non-diabetic patients with CAD (n=122) had lower adiponectin levels than those without CAD (n=110) (4.60 [3.32-6.38] vs 6.08 [4.10-9.88] μg/ml, p<0.001). Multiple logistic regression analysis demonstrated adiponectin independently correlated with the presence of CAD (OR 0.432, 95% CI 0.256-0.728; p=0.002). Conclusions Hypoadiponectinemia is associated with IGT and CAD in non-diabetic men, suggesting that the adiponectin level can provide valuable information regarding the risk of CAD even in non-diabetic subjects. (Circ J 2007; 71: 1703 - 1709)

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Background Beta is an index of arterial stiffness independent of blood pressure. Beta of the thoracic descending aorta (TDA) has been obtained by transesophageal echocardiography (TEE) and the cardio-ankle vascular index (CAVI) is a new noninvasive estimation of β. Methods and Results The purpose of this study was to evaluate the accuracy and usefulness of CAVI and to compare it with other parameters of arteriosclerosis by carotid ultrasound (CU). The instantaneous dimensional change of the TDA on TEE was measured simultaneously with systemic pressure of the brachial artery in 70 patients in sinus rhythm. There were significant correlations between CAVI and age (r=0.65, p<0.01), and CAVI and the β from TEE (Aoβ) (r=0.67, p<0.01). Next, 110 patients with chest pain syndrome underwent CU and measurement of CAVI, intima - media thickness (IMT), plaque score and β. There were significant relationships between CAVI and IMT (r=0.42, p<0.01), and between CAVI and β (r=0.39, p<0.01). CAVI of the group diagnosed with plaque was significant higher than that of the normal group (9.872±1.464 vs 9.038±1.377, p=0.0039). Conclusions CAVI is measured easily and noninvasively and is a new index of arterial stiffness that is independent of blood pressure. (Circ J 2007; 71: 1710 - 1714)

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Background It has been recently suggested that γ-glutamyltransferase (GGT) is independently associated with cardiovascular mortality and atherosclerosis, so the present study evaluated whether GGT is an additional marker of arterial stiffness, independent of other risk factors, in screening cohorts. Methods and Results The 1,387 individuals (741 men, 646 women) who underwent brachial - ankle pulse wave velocity (baPWV) measurement had their serum levels of GGT, creatinine, uric acid, C-reactive protein, lipids, fasting glucose and insulin, and their hepatitis profiles checked. There were statistically significant increments of baPWV according to quartile of GGT, which was statistically significant in women, but not in men. In logistic regression analysis, age, diabetes mellitus, GGT, heart rate, history of hypertension, triglyceride, and systolic blood pressure were significant variables that influenced increased pulse wave velocity (PWV). After age-and blood pressure-adjustment, GGT, homeostatic model assessment-insulin resistance, heart rate, history of hypertension, and metabolic syndrome were significant variables in men, and in women metabolic syndrome and history of hypertension were significant contributors to increased PWV. Conclusion The present study results suggest that serum GGT may be an additional marker of arterial stiffness, especially in men, though the relationship with arterial stiffness was very weak. Further studies are needed to elucidate the mechanism of GGT's contribution to arteriosclerosis and to confirm the current results. (Circ J 2007; 71: 1715 - 1720)

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Background The present study sought to determine if echo-Doppler-derived pulmonary vascular resistance (PVR_echo), net-atrioventricular compliance (Cn) and tricuspid peak systolic annular velocity (Sa), as parameters of right ventricular function, have value in predicting exercise capacity in patients with mitral stenosis (MS). Methods and Results Thirty-two patients with moderate or severe MS without left ventricular systolic dysfunction were studied. After comprehensive echo-Doppler measurements, including PVR_echo, tricuspid Sa and left-sided Cn, supine bicycle exercise echo and concomitant respiratory gas analysis were performed. Measurements during 5 cardiac cycles representing the mean heart rate were averaged. Increment of resting PVR_echo (r=-0.416, p=0.018) and decrement of resting Sa (r=0.433, p=0.013) and Cn (r=0.469, p=0.007) were significantly associated with decrease in %VO₂ peak. The predictive accuracy for %VO₂ peak could increase by combining these parameters as Sa/PVR_echo (r=0.500, p=0.004) or Cn· (Sa/PVR_echo) (r=0.572, p=0.001) independent of mitral valve area, mean diastolic pressure gradients or presence of atrial fibrillation. Conclusions Measurement of PVR_echo, Cn and Sa might provide important information about the exercise capacity of patients with MS. (Circ J 2007; 71: 1721 - 1727)

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Background Although menopause is known to increase cardiovascular risk and mortality, the effect of menopause on cardiac functions has not been investigated in detail. This study investigates the effect of menopause on cardiac functions by tissue Doppler echocardiography (TDE) and myocardial performance index (MPI). Methods and Results A total of 72 postmenopausal and 71 age-matched premenopausal women were enrolled in the study. After conventional echocardiographic parameters were measured, TDE recordings were obtained at the septal, lateral, anterior and inferior side of the mitral annulus, and tricuspid lateral annulus. Systolic velocity (Sm), early and late diastolic velocities (Em and Am) and time intervals were measured and MPI was calculated. A sequentially symptom-limited exercise stress test was performed. Although left ventricular (LV) ejection fraction and end-diastolic and end-systolic diameter were similar in both groups, LV septum and posterior wall thickness were higher in postmenopausal women. Mitral early inflow velocity and mitral early inflow velocity:mitral late inflow velocity ratio were significantly lower in postmenopausal women compared to premenopausal women. LV Sm, and LV and right ventricular (RV) Em:Am ratios were lower in postmenopausal women. MPI calculated by TDE was significantly increased in postmenopausal women. In addition, exercise duration and metabolic equivalent values were significantly lower in postmenopausal women than in premenopausal women. Conclusions Menopause negatively affects MPI and myocardial velocities, both of which provide more quantitative data about myocardial functions. These findings indicate that the hormonal changes in menopause impair LV systolic and diastolic functions and RV diastolic function. (Circ J 2007; 71: 1728 - 1733)

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Background To clarify whether there are age and gender differences in the components contributing to the diagnosis of metabolic syndrome (MS) in the Japanese population. Methods and Results A total of 21,870 individuals (ie, 7,329 men aged 68±8.1 years, body mass index (BMI) 23.2±2.9 kg/m² and 14,541 women aged 66±9.4 years, BMI 22.8±3.3 kg/m²) participated in the study. The subjects were obtained from the general population and examinations were conducted in hospitals located in Kanazawa city. MS was diagnosed according to the Japanese criteria. Information regarding medication is lacking in all participating subjects. Overall, the incidence of MS was 18.4% and 5.78% for men and women, respectively. When analyzed according to age group, the incidence of MS in men did not differ significantly, whereas its prevalence was higher in older women than in younger women. Among the indicators of MS, high blood pressure (BP; high systolic BP and/or high diastolic BP) was the most frequent, followed by dyslipidemia (high triglycerides and/or low high-density lipoprotein-cholesterol (HDL-C)), and high fasting plasma glucose was the least frequently occurring in both genders. In contrast to the high frequency of high BP, isolated high diastolic BP was rare across both genders regardless of age group. Similarly, isolated low HDL-C was quite rare. Conclusions Frequency of the components contributing to the diagnosis of MS differed considerably according to gender and age group in the Japanese population. (Circ J 2007; 71: 1734 - 1737)

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Background There is increasing evidence that both obstructive and central sleep apnea contribute to the progression and prognosis in patients with chronic heart failure (CHF). In the main study of nocturnal home oxygen therapy (HOT) in patients with central sleep apnea because of CHF (CHF-HOT), significant improvements in oxygen desaturation index, apnea - hypopnea index, left ventricular ejection fraction, and specific activity scale were reported following 12 weeks of nocturnal HOT in these patients. Methods and Results The present study is designed to further evaluate the clinical efficacy and cost - benefit of nocturnal HOT according to the results of a follow-up survey on changes in frequencies of hospitalization, emergency visits, and regular outpatient visits by 53 patients undergoing nocturnal HOT for more than 6 month periods. Medical costs were estimated from the DPC-MDC5 charge for hospitalization because of worsening heart failure (HF), and from the standard model case estimation for emergency and regular outpatient visits for HF. To reveal the time-saving benefit following nocturnal HOT, the influence on estimated days spent for hospital-care was also analyzed. The present study revealed significant reduction in frequencies and length of hospitalization (2.1 to 0.5 times/year, 38.7 to 34.6 days, medical cost: -2,686,267 yen), emergency visit (2.5 to 0.7 times/year, -15,984 yen), and regular outpatient visit (17.7 to 12.6 times/year, -6,324 yen) as compared with those before the induction of nocturnal HOT, which resulted in a total medical cost-reduction of 1,854,175 yen/patient/year, even with the additional charge for nocturnal HOT (854,400 yen/patient/year). Furthermore, nocturnal HOT produced a remarkable decline in estimated days spent for hospital-care (88.2 to 21.2 days/patient/year). Conclusion The present analysis calculated a remarkable cost-benefit (1,854,175 yen/patient/year) from the reduction in hospitalization and emergency visits, and also time-saving benefits from an increase in expected days free from hospital-care (67 days/patient/year). (Circ J 2007; 71: 1738 - 1743)

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Background Clinical outcome of heart transplantation in patients with heart failure and ascites has not been reported. Here, the clinical outcome of heart transplantation in patients with heart failure and ascites is evaluated. Methods and Results Between 1989 and 2005, 45 patients with heart failure and ascites underwent an orthotopic heart transplantation. Of the 45 patients, 33 were men (median age 44 years, range 10-63 years). Causes of heart failure included congenital heart disease in 4 patients (9%), dilated cardiomyopathy in 21 patients (47%), rheumatic heart disease in 7 patients (16%), coronary artery disease in 10 patients (22%), and others. Twenty of the 45 patients (44%) had undergone a previous cardiac operation. Hospital mortality occurred in 10 patients (22%) because of bleeding in 4, sepsis with multiple organ failure in 5 and non-diagnostic graft failure in 1 patient. Re-operation for postoperative bleeding occurred in 14 patients (31%). Independent risk factors for hospital death were low serum albumin (odds ratio 0.05; 95% confidence interval 0.003-0.591; p=0.018) and re-operation for bleeding (odds ratio 30.11; 95% confidence interval 2.38-380.26; p=0.009). Conclusions Heart transplantation in patients with heart failure and ascites was associated with high hospital mortality and morbidity. The co-existence of ascites and hypoalbuminemia implied poor prognosis. (Circ J 2007; 71: 1744 - 1748)

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Background The correlation between body mass index (BMI)/obesity and blood pressure/hypertension has not been confirmed in diabetic patients. This study analyzed the association in Taiwanese adult patients with type 2 diabetes mellitus (T2DM). Methods and Results The National Health Insurance data of 89,857 adult patients (41,398 men and 48,459 women; aged ≥18 years with mean ± SD of 62.2±11.3 years) interviewed by questionnaire were analyzed, taking into account the potential confounding of age, sex, diabetic duration, smoking and parental hypertension. Prevalence of obesity (BMI ≥25 kg/m²) was 39.3% and 41.7% in the diabetic men and women, respectively; and hypertension was 54.5% in both sexes. Hypertension increased significantly with increasing age and BMI. The adjusted odds ratio (OR) for hypertension for every 1 kg/m² increment of BMI was 1.16 (1.15-1.17) and 1.13 (1.12-1.14) for men and women, respectively. The correlation between BMI and hypertension/blood pressure extended throughout BMI levels to the nonobese range. For men, adjusted OR for BMI <18.5, 18.5-22.9, 23.0-24.9, 25.0-29.9 and ≥30.0 kg/m² were 1.00, 1.23 (1.07-1.41), 1.78 (1.55-2.05), 3.06 (2.66-3.53) and 6.59 (5.56-7.82), respectively; and were 1.00, 1.09 (0.97-1.22), 1.49 (1.32-1.68), 2.32 (2.06-2.60), 4.40 (3.84-5.05), respectively, for women. For every 1 unit BMI increase in patients without a hypertension history, the systolic and diastolic blood pressures significantly increased by 0.618 and 0.447 mmHg for men; and by 0.637 and 0.462 mmHg, respectively, for women. Conclusions BMI/obesity is significantly linked to blood pressure/hypertension throughout the range of BMI in diabetic patients in either sex regardless of a previous hypertension history. (Circ J 2007; 71: 1749 - 1754)

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Buckground A higher heart rate (HR) is associated with cardiovascular morbidity and mortality. Hypertension is an important cardiovascular risk factor. The present study evaluated whether a higher HR was associated with the development of hypertension in normotensive, screened subjects. Methods and Results Among normotensive participants of a 1-day health evaluation in 1997, we studied those who also participated in the program in 2000 (n=4,331; 2,823 men (65%), 1,508 women; mean age 47±9 years). Subjects were divided into 4 groups based on their HR in 1997: quartile 1 (HR ≤58, n=1,033), quartile 2 (59≤HR ≤64, n=1,162), quartile 3 (65≤HR ≤70, n=1,012), and quartile 4 (HR ≥71, n=1,124). The 3-year frequency of developing hypertension in 2000 was 4.5% for quartile 1, 6.8% for quartile 2, 6.0% for quartile 3, and 7.2% for quartile 4 (p=0.0424). Subjects with a higher HR were likely to have a greater number of metabolic syndrome components and a higher incidence of proteinuria. In a logistic regression analysis adjusted for gender, age, alcohol consumption, exercise, atherosclerotic risk factors, and lifestyle, the odds ratios (95% confidence intervals) for the development of hypertension were 1.53 (1.04-2.24) for quartile 2, 1.35 (0.90-2.02) for quartile 3, and 1.61 (1.10-2.37) for quartile 4, compared with quartile 1 as a reference. Conclusion A higher HR was associated with the development of hypertension. Subjects with a higher HR should be followed carefully, even if they are normotensive. (Circ J 2007; 71: 1755 - 1760)

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Background Associations between pathogens and hypertension (HT) has been reported, but few studies have focused on the relationship between aggregate pathogens and HT. The present study explored whether the risk of HT is associated with each pathogen (defined as Chlamydia pneumoniae (C. pneumoniaee), Mycoplasma pneumoniae (M. pneumoniae), Helicobacter pylori (H. pylori) and Coxsackie virus) or with aggregate pathogens in Chinese Mongolians. Methods and Results One thousand and thirty Chinese Mongolians aged 30 years or more were recruited, including 488 hypertensive and 942 normotensive subjects. Enzyme-linked immunosorbent assay was used to detect IgG antibodies for C. pneumoniaee, M. pneumoniae, H. pylori and Coxsackie virus. The seroprevalence of Coxsackie virus was significantly associated with HT (odds ratio (OR) 3.7 after adjustment for risk factors), but no significant association was found for C. pneumoniae, M. pneumoniae and H. pylori (OR 1.32, 0.75 and 1.19, respectively). The results also showed that the risk of HT was associated with the aggregate pathogens: it increased with the increasing number of pathogens, and the ORs were 1.629, 2.653, 2.129, and 5.146 for 1, 2, 3 and 4 pathogens, respectively, after controlling for risk factors. Conclusion The risk of HT is associated with Coxsackie virus and aggregate pathogen load. The mechanism(s) underlying the associations remain to be elucidated further. (Circ J 2007; 71: 1761 - 1764)

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Background Population-based analysis shows that deaths from pulmonary embolism (PE) are increasing in the older age groups, but it is unclear to what degree PE contributes to death in different ages and gender. Methods and Results Potential contribution factors for all PE and for critical PE (in which PE was the primary cause of death or the main diagnosis) were examined in 396,982 autopsy cases. For all PE, odds ratio (OR) in males was 0.61 (95% confidence interval (CI) 0.59-0.64, p<0.0001), compared with that in females. ORs were 1.10 (95% CI 1.05-1.14, p<0.0001) in 1991-1994 and 1.19 (95% CI 1.14-1.25, p<0.0001) in 1995-1998, compared with those in 1987-1990. ORs for ages 0-9 and 40+ were significantly low compared with that for ages 20-39. For critical PE, similar results were obtained. Pregnancy and/or delivery were found in 38.5% in cases of critical PE in females aged 20-39. Conclusion Compared with other age groups, PE contributed more to deaths in those aged 20-39 years. In recent years, deaths from PE have been slightly but significantly increasing. The incidence of clinically diagnosed critical PE also has been increasing. (Circ J 2007; 71: 1765 - 1770)

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Background Pulmonary artery pressure (PAP) is reduced dramatically after pulmonary thromboendarterectomy in patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, it is unclear whether pulmonary artery compliance increases in conjunction with the reduction in PAP. Pulmonary artery compliance may affect right ventricular afterload and prognosis. Methods and Results In 33 patients with CTEPH (9 men, 22-76 years), changes in the tricuspid regurgitation pressure gradient (TRPG) and the acceleration time (ACT) of pulmonary artery flow (a surrogate parameter of pulmonary artery compliance) were examined before and after pulmonary thromboendarterectomy using echocardiography to clarify factors affecting the changes. At 6 months, both TRPG and ACT normalized (≤30 mmHg, ≥100 ms, respectively) in 25 patients (group A) but not in 8 (group B). In group B, there were 5 with normal TRPG and shortened ACT at 6 months that normalized at 17±3 months. Group A patients showed shorter disease period and shorter period without anticoagulation than group B patients (p=0.04, 0.02 respectively). All patients in group A had the proximal type, and 2 patients of group B had the distal type (p=0.05). Clinical improvement was more remarkable in group A. Conclusions The recovery of PAP and the ACT of pulmonary artery flow was not always concordant after pulmonary thromboendarterectomy, suggesting a presence of a time lag in the recovery between pressure and compliance in some patients. A long period of CTEPH, a long period without anticoagulation and the distal embolism type may be predictive factors of an unfavorable operative result with reduced pulmonary artery compliance, and hence poor recovery of clinical performance. (Circ J 2007; 71: 1771 - 1775)

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Background The present study analyzes a 15-year experience of repairing persistent truncus arteriosus (PTA) with a consistent policy of right ventricular outflow tract (RVOT) reconstruction (ie, direct anastomosis). Methods and Results This retrospective study included 13 consecutive patients with PTA (8 type I PTA, 5 type II) who underwent primary repair from September 1992 to December 2006. Median age and body weight at surgery were 21 days and 2.9 kg, respectively. All but 1 patient underwent RVOT reconstruction by direct anastomosis with a monocusp patch. There were 2 operative deaths (12%). No patient had a pulmonary hypertensive crisis. The median duration of ventilation was 5 days. Another patient died from cardiogenic shock resulting from late cardiac tamponade 2 months after surgery. Four patients (40%) required balloon angioplasty and 5 (50%) required re-operation for branch pulmonary artery and/or conduit obstruction during the median follow-up period of 70 months (44-174 months). Freedom from all re-interventions and re-operation at 5 years was 50% (95% confidence limits, 19-81%) and 60% (95% confidence limits, 30-91%), respectively. Conclusions Reasonable early and long-term results can be achieved with direct anastomosis. Further reduction of the re-intervention rate could be attained by refining the surgical techniques and catheter intervention strategies. (Circ J 2007; 71: 1776 - 1780)

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Background There is a high incidence of restenosis and aneurysm formation after balloon angioplasty for discrete native coarctation in neonates and young infants, and so the techniques remains controversial in this group of patients because its clinical validity, particularly in comparison with surgery, has not been well established. Methods and Results From January 1999 to October 2005, group A (17 patients [8 males, 9 females] <3 months old ranging from 0.2 to 2.9 months, with a body weight of 2.5-5.5 kg) and group B (11 patients [5 males, 6 females] >3 months old ranging from 5.5 months to 6.4 years, with a body weight of 7.8-21 kg) with discrete native coarctation who underwent balloon angioplasty and were included in this study. There were 13 (76%) successes in group A, and 10 (90%) successes in group B for the initial balloon angioplasty. There was no significant difference in success rate between groups A and B (p>0.05). There were 9 (69%) cases of restenosis patients in group A, and 2 (20%) in group B, a significant difference between the 2 groups (p<0.05). In group A, 1 patient showed aneurysm formation after angioplasty, 1 (5.8%) showed femoral artery obstruction and 2 (11%) showed reduced pulses. Conclusions Balloon angioplasty of discrete native coarctation is effective in patients both younger and older than 3 months. However, thea rates of restenosis, aneurysm formation, and approach artery injury are higher in patients younger than 3 months old when compared with patients aged over 3 months. These complications should be considered when performing balloon angioplasty in patients less than 3 months of age. (Circ J 2007; 71: 1781 - 1784)

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Background There is little data on the long-term effects of continuous intravenous epoprostenol for children with idiopathic pulmonary arterial hypertension (IPAH) in Japan. Methods and Results Thirty-one IPAH patients younger than 18 years old who had begun epoprostenol therapy at Toho University Omori Medical Center between January 1999 and June 2004 were reviewed. During a mean follow up of 3.4 years, the rate of those who survived or did not undergo a lung transplantation among the 27 patients who received home infusion therapy of epoprostenol was 100% at 1 year, 96.3% at 2 years, and 79.4% at 3 years. In 82% of survivors, the World Health Organization functional class was changed from III or IV to II according to improvements in the plasma brain natriuretic peptide level and the distance walked in 6 min during the follow-up period. In most cases, mean pulmonary artery pressure and the ratio of pulmonary to systemic vascular resistance remained high, although the cardiac index had improved to within a normal range 1 year after the initiation of epoprostenol. Therefore, sildenafil was administered as an additional therapy to 16 patients who presented with sustained severe PAH. Conclusions Continuous IV epoprostenol certainly improves survival and exercise tolerance in childhood IPAH, although the improvement of pulmonary vascular resistance regardless of long-term epoprostenol therapy is insufficient. Therefore, the addition of a new drug, such as sildenafil, is recommended to be administered in adjunction with epoprostenol. (Circ J 2007; 71: 1785 - 1790)

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Background The aim of this study was to investigate the effect of a revision of the fever criterion for initial intravenous immunoglobulin (IVIG) treatment, and cardiovascular sequelae, in the new Japanese diagnostic criteria for Kawasaki disease. Methods and Results Patients who were reported in the 16^th and 18^th nationwide surveys in Japan were analyzed. New criteria group comprised patients who received the diagnosis of Kawasaki disease in the 18^th nationwide survey (n=18,789). Old criteria group was comprised patients who received their diagnosis in the 16^th nationwide survey (n=15,017). The difference between the new and old criteria for complete cases was only 1%. The proportion of patients who were treated with IVIG within 4 days of illness onset in the new criteria group was significantly lower than in the old criteria group (27.7% vs 30.7%). Multivariate logistic regression analysis identified criteria sex, age, recurrence, diagnosis, last day of initial IVIG and additional IVIG treatment as significant independent factors for cardiovascular sequelae. Conclusions The guideline revision improves diagnostic sensitivity somewhat, but reflects the clinical reality of the disease that approximately 30% of patients are treated with IVIG within 4 days of illness onset. (Circ J 2007; 71: 1791 - 1793)

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Background To establish the criteria for selecting a mitral annuloplasty ring of the correct size, the dimensions of the mitral valve orifice were analyzed in cadaveric hearts. Materials and Results From December 2000 to July 2006, the mitral valve diameter [D_M (Obs)] and Z-values [D_M (Z); standardized value based on Rowlatt's criteria], the angles of the trigones (θ_Tg) and commissures (θ_Com) and the intertrigonal distance [L (T)] were measured in 82 fresh cadaveric hearts from cases with variable causes of death (mean age 64.8±15.7 years; body surface area [BSA] 1.51±0.21 m²). D_M (Obs), D_M (Z) and L (T) were 2.8±0.5 cm, 1.16±0.98, and 1.8±0.2 cm, respectively. Theta _Tg and θ_Com averaged 76±13 and 121±11 degrees, respectively. There was a significant inverse linear relationship between D_M (Z) and θ_Tg [θ_Tg =-10× D_M (Z) +88] and a significant logarithmic correlation between L (T) and BSA [L (T) =0.54×Ln (BSA) +1.55]. The anterior annular length and L (T) remained unchanged. Conclusion In non-dilated cadaveric hearts, the trigones were located at one-quarter of the mitral annulus, so the appropriate length of the posterior annuloplasty band should be adjusted to L (T) ×3.33. (Circ J 2007; 71: 1794 - 1799)

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Background There is an increased risk of automobile accidents in patients with some cardiovascular disorders and licensing authorities have imposed certain restrictions on such persons. Experience assessing fitness to drive among drivers with cardiovascular disorders, and the relevance of other associated medical conditions among drivers assessed as unfit, are reported here. Methods and Results The study included 5,234 drivers attending 2 Spanish Medical Driver Test Centres to assess their fitness to drive. Information regarding sociodemographic aspects, driving patterns, medical conditions, medication use and alcohol consumption patterns was recorded: 11.6% of the drivers had a cardiovascular disorder that potentially impaired fitness to drive, 82.5% were found fit to drive, 15.9% were fit to drive with restrictions and 1.6% were unfit. The 10 unfit patients with cardiovascular disorders were primarily considered unfit because of their associated ophthalmologic and medical comorbidities, but the cardiovascular disorders were a contributing factor. Conclusion Most (98.4%) drivers with cardiovascular disorders will be completely fit to drive or fit to drive with restrictions. There is a need for a personalized evaluation of fitness to drive for each driver/patient, taking into account such aspects as the associated pathology, the taking of medicinal drugs and alcohol consumption. (Circ J 2007; 71: 1800 - 1804)

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Background It has been shown that pilsicainide terminates atrial fibrillation (AF) by pharmacologic pulmonary vein (PV) isolation. However, whether it can prevent AF induction originating from the PV by the same mechanism is still uncertain. Methods and Results Rapid pacing from the left superior PV (LSPV) and the right atrial free wall (RAF) was performed to induce AF during electrical stimulation of both cervical vagal nerves in 6 anesthetized dogs and during the infusion of acetylcholine (ACh) in 8 isolated atria. Rapid pacing induced AF in all dogs, regardless of the pacing site, before pilsicainide. Pilsicainide (1 mg/kg) prevented AF during rapid pacing from the LSPV, with an impulse conduction block between the LSPV and the left atrial free wall (LAF). However, the same dose of pilsicainide did not prevent AF when pacing was performed from the RAF. Pilsicainide partially restored the action potential duration shortened by ACh infusion and prevented AF with an impulse conduction block at the LSPV-left atrial junction in all isolated preparations tested. Conclusion The results suggest that (1) impulse conduction block at the LSPV-LA junction is the underlying mechanism of pilsicainide-induced prevention of vagally-induced AF originating from the LSPV and (2) pilsicainide is more effective at preventing AF originating from the LSPV than that from the RA. (Circ J 2007; 71: 1805 - 1814)

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Background It was investigated whether edaravone, a potent free radical scavenger, would protect against anthracycline-induced cardiotoxicity and prevent cardiac function deterioration. Methods and Results Cultured neonatal rat cardiomyocytes were stimulated by daunorubicin 1 μmol/L either with or without edaravone or superoxide dismutase mimetic Mn (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP). Cell viability was estimated by measuring the amount of lactate dehydrogenase (LDH) released into the culture medium. Apoptosis was determined by a caspase-3 activity assay and a histone - DNA complex fragment assay. To investigate whether edaravone interfered with daunorubicin's anti-tumor effect, daunorubicin and edaravone were added to human leukemia K562 cells, and the surviving cells were counted. In addition, edaravone's in vivo effect was evaluated using Sprague - Dawley rats. A total of 15 mg/kg doxorubicin was injected intraperitoneally either with or without simultaneous edaravone injection. Two and 6 weeks after the final injection, left ventricular diastolic diameter and left ventricular fraction shortening were assessed echocardiographically. The LDH assay showed that edaravone significantly inhibited LDH release from cardiac myocytes (p=0.0428). The caspase-3 activity and histone - DNA complex fragment assays demonstrated that edaravone's apoptosis suppression effect was much weaker than that of MnTMPyP. The in vivo study showed that edaravone prevented doxorubicin-induced cardiac deterioration. Finally, edaravone was found to not affect daunorubicin's anticancer effect on K562 cells. Conclusions Edaravone protects cardiomyocytes from anthracycline-induced cardiotoxicity via an anti-necrotic rather than an anti-apoptotic effect. (Circ J 2007; 71: 1815 - 1820)

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After successful surgical repair in patients with aortic coarctation, the early onset of cardiovascular diseases is an important subsequent complication and one of the causes is the enhanced aortic pressure wave reflection. Balloon angioplasty has become established as an effective alternative to surgery, but there have been no reports regarding pressure wave reflection after balloon dilatation in patients with aortic coarctation. A 29-year-old patient with aortic coarctation was admitted for angioplasty, which was performed successfully. Six months later, catheter examination demonstrated enhanced aortic pressure wave reflection, although there was no pressure difference. After balloon dilatation patients with aortic coarctation may be also at high risk for future cardiovascular diseases. (Circ J 2007; 71: 1821 - 1822)

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A case of advanced cardiac amyloidosis was treated with thalidomide. The patient showed early and significant improvement of diastolic cardiac function, as well as symptoms. (Circ J 2007; 71: 1823 - 1825)

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There are a few reports of cardiac surgery in patients with myelodysplastic syndrome (MDS). It is difficult to control bleeding and prevent infection in the presence of pancytopenia. Interstitial pneumonia, which is treated by steroid medication, is also a risk factor in cardiac surgery. Aortic valve replacement was successfully performed in a patient with severe thrombocytopenia associated with MDS, interstitial pneumonia and scleroderma. (Circ J 2007; 71: 1826 - 1828)

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Background Oral prostacyclin analogs can improve the prognosis of patients with mild to moderate pulmonary arterial hypertension (PAH), but because they often provoke adverse effects, such as flushing and dizziness, administering the optimal dose can be difficult. Methods and Results In the present study, a novel long-acting oral beraprost (TRK-100STP: 0-360 μg/day for 12 weeks) was administered to 4 patients with mild to moderate PAH. The patients tolerated the drug well with mild adverse manifestations and negligible effects on the systemic circulation. In contrast, pulmonary vascular resistance decreased by 27±12% and the 6-min walk test distance increased by 11±11%. Conclusions TRK-100STP is a novel option in the medical management of patients with PAH. (Circ J 2007; 71: 1829 -1831)

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