Although much progress has been made in reducing mortality from ischemic cardiovascular disease, this condition remains the leading cause of death throughout the world. This might in part be due to the fact that over half of patients have a catastrophic event (heart attack or sudden death) as their initial manifestation of coronary disease. Contributing to this statistic is the observation that the majority of myocardial ischemic episodes are silent, indicating an inability or failure to sense ischemic damage or stress on the heart. This review examines the clinical characteristics of silent myocardial ischemia, and explores mechanisms involved in the generation of angina pectoris. Possible mechanisms for the more common manifestation of injurious reductions in coronary flow; namely, silent ischemia, are also explored. A new theory for the mechanism of silent ischemia is proposed. Finally, the prognostic importance of silent ischemia and potential future directions for research are discussed. (Circ J 2009; 73: 785 - 797)

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In patients with non-ST-segment elevation acute coronary syndromes, early risk stratification is crucial for appropriate management of this condition and for deciding whether early invasive strategies should be adopted. The electrocardiogram (ECG) has been extensively used for risk stratification, and the presence of ST-segment depression is an especially strong predictor of poor outcomes. Furthermore, quantitative analysis of ST-segment depression, ie, the degree and extent of ST-segment depression, and the time from symptom onset to the evaluation of ECG provide important information on prognosis. ST-segment elevation in lead aV_R in addition to ST-segment depression in other leads is a very valuable marker of left main and/or 3-vessel disease. This review explores the clinical importance of the ECG in the current interventional era. (Circ J 2009; 73: 798 - 805)

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Protein biomarkers play an essential role in diagnosis of cardiovascular disease. This review will mainly focus on recent development of biomarkers, namely those for aortic dissection and oxidized LDL markers, but also on new aspects including efforts to use mass spectrometry in clinical medicine, while discussing on historical perspectives to better illustrate our relative contributions and progress. (Circ J 2009; 73: 806 - 809)

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Mutations in the cardiac sodium channel gene SCN5A are responsible for a spectrum of hereditary arrhythmias, including type-3 long QT syndrome (LQT3), Brugada syndrome (BrS), conduction disturbance and sinus node dysfunction. These syndromes were originally regarded as independent entities with distinct clinical manifestations and biophysical properties, but recent evidence shows considerable clinical overlap, implying a new disease entity known as an overlap syndrome of cardiac sodium channelopathy. Class IC sodium-channel blockers often induced the BrS phenotype in some patients with LQT3, confirming the clinical overlap of LQT3 and BrS. It also raises a concern about the safety of the class IC drug and questions about the determinants of overlap. Here, an overview is given of current knowledge on the clinical features, prevalence, and molecular and biophysical mechanisms underlying overlap syndrome to gain more insight into this complex issue and generate better therapeutic strategies for patient management. (Circ J 2009; 73: 810 - 817)

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Background: Aortic aneurysms are found in 5-20% of patients with acute aortic dissection (AAD).Coexisting aortic aneurysms might potentially influence the incidence of AAD. The purpose of this study was to elucidate the role of coexistent aortic aneurysms in AAD. Methods and Results: A total of 140 patients with AAD were enrolled in the present study. Clinical characteristics of the patients were evaluated in relation to the locations of aortic segments affected by the dissection as well as of the coexistent aortic aneurysm. Among the 140 study patients, 34 (24%) had true aortic aneurysms. Patients with coexistent aortic aneurysm were significantly older than those without (72 ±11years vs 65 ±14 years, P=0.012) and had higher incidence of thrombosed false lumen (62% vs 38%, P=0.017), and coronary artery disease (26% vs 8%, P=0.006). Twenty-two of these 34 (65%) patients had a thoracic aortic aneurysm (TAA), and this frequency of TAA was much higher than that observed in the general population. Furthermore, among all patients with AAD, 12 patients (9%) might be associated with development of AAD. Conclusions: The current study showed that nearly one-quarter of AAD patients had coexisting true aortic aneurysms, and suggests that TAA are likely to be associated with development of AAD. (Circ J 2009; 73: 822 - 825)

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Background: Recognizing the relative location of the esophagus to the left atrial posterior wall (LAPW) is required to avoid esophageal injury during atrial fibrillation ablation. Methods and Results: The 24 patients undergoing circumferential pulmonary vein isolation (CPVI) each had the geometry of their left atrium (LA) and esophagus constructed by a noncontact mapping system with EnSite version 6.0J. The esophageal course relative to the LAPW was found to be to the left in 12, middle in 8, right in 2, and obliquely left-to-right in 2 patients, and in 13 patients (54%) it was located on or near either the left or right CPVI line. The mean distance between the esophagus and LAPW was shorter at the bottom line of the LAPW connecting both inferior pulmonary veins (3 ±3 mm) than at the LA roof line connecting both superior pulmonary veins (6 ±6 mm, P<0.01). Conclusions: The location of the esophagus relative to the LAPW varies with the patient, but a close location to either CPVI line was found in approximately 50% and a close location between the esophagus and LAPW was found in the inferior and middle locations in most patients. (Circ J 2009; 73: 826 - 832)

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Background: The safety and efficacy of the transradial approach for radiofrequency catheter ablation (RFCA) of left-sided atrioventricular accessory pathways (APs) was evaluated in the present study. Methods and Results: Included were 40 consecutive patients with type A Wolff-Parkinson-White (WPW) syndrome who underwent RFCA via the radial artery route, and 30 patients with type A WPW syndrome who underwent RFCA via the transfemoral approach (controls) were retrospectively chosen for control. All 45 APs in the 40 patients were successfully ablated: 35 APs were successfully blocked with 1 ablation attempt, and the other 10 APs were ablated after 2-4 attempts. Compared with the transfemoral approach, the total procedure time for the transradial approach was longer (40 ±7.7 vs 32.4 ±8.7 min, P<0.05) and the fluoroscopic time was similar (7.2 ±2.2 vs 7.9 ±3.9 min, P>0.05). There were no vascular complications in the transradial group, but 2 patients in the transfemoral developed local hematoma. There was no recurrence of arrhythmia in either group. Conclusions: The transradial approach is a safe and effective access for RFCA of left-sided APs. (Circ J 2009; 73: 833 - 837)

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Background: Some supraventricular tachycardias could be ablated from the non-coronary sinus of Valsalva (NSV). However, the characteristics of the NSV electrograms have not been clarified. Methods and Results: A quantitative analysis of the NSV electrograms was performed in 5 patients with tachycardias arising from near the atrioventricular node (AVN) and the His-bundle region, and in 20 control subjects. In another 7 control subjects, the NSV electrograms were compared with those recorded at the left and right sinus of Valsalva (LSV and RSV). The NSV electrograms during sinus rhythm had a larger atrial amplitude than ventricular amplitude, and the ratio of the atrial amplitude to the ventricular amplitude was usually >1, which was apparently different from the LSV and RSV electrograms. A tiny but distinct His-bundle deflection was sometimes recorded at the NSV during sinus rhythm while it was not during the tachycardia. The distance to the His-bundle region in the anteroseptal right atrium was shorter from the NSV than from the RSV or LSV. Conclusions: The precise identification of the catheter position at the NSV is possible using the characteristics of the electrograms. Much attention should be paid during ablation to the NSV because of its vicinity to the AVN and His-bundle region. (Circ J 2009; 73: 838 - 845)

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Background: The prothrombotic state in non-valvular atrial fibrillation (NVAF) increases the risk of thromboembolic events. It is also well known that a prothrombotic state exists in renal failure. Hemostatic disorders play a role in thromboembolic mortality in both NVAF and renal failure. However, little is known about the influence of renal function on hemostasis in patients with NVAF. Methods and Results: A total of 190 consecutive outpatients with NVAF who were not receiving anticoagulant therapy were enrolled in the present study. Patients were stratified in groups based on estimated glomerular filtration rate (eGFR). Plasma concentrations of thrombin-antithrombin complex (TAT) and D-dimer were measured and the influence of renal function on coagulation and fibrinolysis was assessed. A relatively weak and inverse relationship of eGFR to TAT and D-dimer was observed (r=0.28, P=0.0001; r=0.30, P<0.0001). Both mean TAT and D-dimer concentrations in groups gradually and significantly increased as eGFR decreased (P<0.0001). On multivariate regression analysis, decreased eGFR concentration was a significant predictor for elevation of TAT (P<0.05) and D-dimer (P<0.01) in patients with NVAF. Conclusions: The enhanced coagulation activation appeared to be related to a reduction in residual renal function in patients with NVAF. This suggests that decreased renal function might be a candidate predictor of thromboembolic events in patients with NVAF. (Circ J 2009; 73: 846 - 850)

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Background: Autonomic neural intervention is a promising tool for modulating the circulatory system thereby treating some cardiovascular diseases. Methods and Results: In 8 pentobarbital-anesthetized cats, it was examined whether the arterial pressure (AP) could be controlled by acupuncture-like hind-limb electrical stimulation (HES). With a 0.5-ms pulse width, HES monotonically reduced AP as the stimulus current increased from 1 to 5 mA, suggesting that the stimulus current could be a primary control variable. In contrast, the depressor effect of HES showed a nadir approximately 10 Hz in the frequency range between 1 and 100 Hz. Dynamic characteristics of the AP response to HES approximated a second-order low-pass filter with dead time (gain: -10.2 ±1.6 mmHg/mA, natural frequency: 0.040 ±0.004 Hz, damping ratio 1.80 ±0.24, dead time: 1.38 ±0.13 s, mean ± SE). Based on these dynamic characteristics, a servo-controlled HES system was developed. When a target AP value was set at 20 mmHg below the baseline AP, the time required for the AP response to reach 90% of the target level was 38 ±10 s. The steady-state error between the measured and target AP values was 1.3 ±0.1 mmHg. Conclusions: Autonomic neural intervention by acupuncture-like HES might provide an additional modality to quantitatively control the circulatory system. (Circ J 2009; 73: 851 - 859)

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Background: Long-term outcome and the factors associated with restenosis after endovascular treatment (EVT) for iliac artery lesions in peripheral arterial disease (PAD) were evaluated. Methods and Results: EVT was performed for 487 lesions (TransAtlantic Inter-Society Consensus-II (TASC-II) Type-A: 275, B: 115, C: 37, and D: 60) in 436 PAD patients. The initial success rates for Type-B and Type-D lesions were lower than for Type-A lesions (P<0.05). The 3-, 5- and 10-year patency rates were 67%, 54% and 50%, respectively, with plain-old balloon angioplasty (POBA), and 88%, 82% and 75%, respectively, for stenting after suboptimal POBA, showing a significantly higher patency after treatment with a stent (P<0.001). With POBA, the long-term patency for Type-C/D lesions was lower than for Type-A/B lesions (P<0.05), but the patency after stenting did not differ significantly between Type-C/D and A/B. In the univariate analysis, the TASC-II classification, lesion length, pre- and post-procedural stenosis rates and stent use were found to be significant factors associated with restenosis (P<0.05). In the multivariate analysis, stent use (hazard ratio (HR) 0.345, confidence interval (CI) 0.193-0.616, P<0.001) and the post-procedural stenosis rate (HR 1.015, CI 1.001-1.030, P<0.05) were significantly associated with restenosis. Conclusions: Stent use and a low residual stenosis rate are significantly associated with patency, and favorable long-term patency can be obtained with stent placement for selected TASC-II Type-C/D lesions. (Circ J 2009; 73: 860 - 866)

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Background: There is limited information about optimal management of drug-eluting stent (DES) restenosis. This study evaluated the incidences of re-restenosis and re-target lesion revascularization (TLR) after the treatment of sirolimus-eluting stent (SES) restenosis. Methods and Results: A total of 102 lesions in 101 patients who underwent TLR for SES restenosis were classified according to: (1) focal (lesion length ≤10 mm) or non-focal restenosis (>10 mm); and (2) use of DES for TLR: (1) focal restenosis treated with DES (focal-DES, n=40); (2) focal restenosis treated by balloon angioplasty (focal-balloon, n=31); (3) non-focal restenosis with DES (non-focal-DES, n=17); and (4) non-focal restenosis by balloon angioplasty (non-focal-balloon, n=14). Re-restenosis and re-TLR were observed in 6 (19.4%) and 5 lesions (12.5%) of the focal-DES group, in 13 (65.0%) and 11 (35.5%) of the focal-balloon group, in 7 (50.0%) and 6 (35.3%) of the non-focal-DES group, and in 8 (61.5%) and 7 (50.0%) of the non-focal-balloon group, respectively (P<0.05 for restenosis and TLR between the focal-DES group and other groups). Conclusions: Re-DES implantation for focal DES restenosis results in lower re-restenosis and re-TLR rates compared to re-DES implantation for non-focal DES restenosis or conventional balloon angioplasty either for focal or non-focal DES restenosis. (Circ J 2009; 73: 867 - 871)

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Background: To prospectively investigate the predictive value of the preoperative C-reactive protein (CRP) concentration for major postoperative complications following off-pump coronary artery bypass (OPCAB) surgery. Methods and Results: From January 2007 to December 2007, 185 consecutive patients scheduled for elective OPCAB surgery were allocated to a low-CRP group (n=137, CRP <0.3 mg/dl) and a high-CRP group (n=48, CRP ≥0.3 mg/dl). The incidence of major postoperative complications, defined as postoperative myocardial infarction, and 5 major morbidity endpoints including permanent stroke, renal dysfunction, any cardiac surgery reoperation, ventilation for more than 48 h, and deep sternal wound infection were assessed and compared. Multivariate logistic regression was used to determine the predictors of major postoperative complications. Patients in the high-CRP group had a significantly higher overall incidence of major postoperative complications, particularly renal dysfunction. In the multivariate logistic regression model, adjusting all the significant univariate predictors, baseline CRP >0.3 mg/dl and preoperative chronic renal failure (CRF) remained as significant independent predictors of major postoperative complications. Conclusions: Elevated preoperative CRP level and/or preoperative CRF indicate increased risk of developing major postoperative complications, particularly acute postoperative renal dysfunction in patients undergoing OPCAB surgery. (Circ J 2009; 73: 872 - 877)

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Background: Although the metabolic syndrome (MetS) is considered to be caused primarily by visceral fat accumulation, epidemiological evidence is lacking as to whether or not obesity is an essential element in the syndrome. Methods and Results: Between 1990 and 2005, the Japan Public Health Center-based Prospective (JPHC) Study conducted baseline measurements of metabolic risk factors in 12,412 men and 21,639 women, aged 40-69 years, with no history of cardiovascular disease (CVD) or cancer. To clarify the role of obesity, which the definition of MetS in Japan has adopted as an essential criterion, clustering of risk factors in data grouped according to overweight condition was examined. During a 12.3-year follow-up there were 2,040 deaths, including 947 from cancers and 304 from CVD. MetS significantly increased the hazard ratios for all-cause mortality in women and CVD mortality in men. Non-overweight with ≥2 risk factors had a similar impact on all-cause and CVD mortality. Clustering of metabolic factors caused a linear increase in the hazard ratios for mortality. Conclusions: MetS caused moderate increases in all-cause and CVD mortality. However, the MetS definition requiring obesity may not necessarily identify non-overweight individuals who have a high mortality risk and are more prevalent than subjects with MetS. (Circ J 2009; 73: 878 - 884)

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Background: The association of elevated serum uric acid (UA) with cardiovascular events in patients with severe coronary artery stenosis was examined. Methods and Results: Patients with stenosis ≥75% (n=8,832) were followed for "all events" (cardiovascular events and all-cause mortality) for 3 years. The group was divided into quartiles based on baseline UA level. The incidence rate of all events was significantly different among quartiles (58.3, 56.5, 61.2, 76.3/1,000 patients-year, P<0.001). Cox's proportional hazard regression analysis showed that the hazard ratio (HR) for all events was 1.25 [95% confidence interval (CI): 1.07-1.45, P<0.01] in the highest quartile (UA ≥6.8 mg/dl). The group in which UA increased ≥1.0 mg/dl after 6 months had significantly higher cardiovascular events rate than the group in which UA did not change (70.6 vs 58.8/1,000 patients-year, P=0.042). Propensity score matching was performed and 4,206 patients were divided into the highest quartile and the rest. High UA remained an independent predictor of all events (HR 1.25, 95%CI 1.06-1.43). However, no significant difference was observed between the group with increased UA ≥1.0 mg/dl and the group with unchanged UA level. Conclusions: Elevated UA is an independent predictor of cardiovascular events and all-cause mortality combined in patients with coronary artery stenosis. (Circ J 2009; 73: 885 - 891)

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Background: It was reported previously that 30 min administration of adrenomedullin (AM) improves hemodynamics in chronic stable heart failure patients. The present study was designed to examine whether long-term AM + human atrial natriuretic peptide (hANP) administration can be used as a therapeutic drug in patients with acute decompensated heart failure (ADHF) in clinical setting. Methods and Results: Seven acute heart failure patients (74 ±5 years) with dyspnea and pulmonary congestion were studied. AM (0.02 μg · kg^-1 · min^-1) + hANP (0.05 μg · kg^-1 · min^-1) was infused for 12 h and then hANP (0.05 μg · kg^-1 · min^-1) was infused for 12 h. Hemodynamic, renal, hormonal and oxidative stress responses were evaluated. AM + hANP significantly reduced mean arterial pressure, pulmonary arterial pressure and systemic and pulmonary vascular resistance without changing heart rate, and increased cardiac output for most time-points compared with those at baseline. In addition, AM + hANP reduced aldosterone, brain natriuretic peptide and free-radical metabolites compared with those at baseline (all P<0.05). AM + hANP increased urine volume and U_NaV compared with baseline data. Conclusions: In this small, pilot trial, AM + hANP therapy had beneficial hemodynamic and hormonal effects in ADHF. Intravenous infusion of AM with hANP could be used as a therapeutic drug in ADHF. These data are preliminary and require confirmation in a larger clinical study. (Circ J 2009; 73: 892 - 898)

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Background: To determine the individual effect of abnormalities in blood pressure (BP) circadian rhythm (nondipping status (NDS), increased morning BP (MBP) or increased MBP surge (MBPS)) on target organ damage (TOD) and which of these is more closely related to TOD in normotensives. Methods and Results: The 24-h ambulatory BP monitoring (ABPM) and echocardiography were performed and urinary albumin excretion (UAE) was measured in 47 dipper (28 women, mean age 45.8 ±9.3) and 32 non-dipper (25 women, mean age 49.1 ±8.3 years) normotensive subjects. The left ventricular mass index (LVMI) was higher in non-dipper group (103.8 ±24.1 vs 91.6 ±23.5 g/m², P=0.03). UAE in non-dipper group was higher, but the difference between the two was not statistically significant (18.9 [10.3, 28.9] vs 14.1 [7.5, 23.8], P=0.11). In multivariate analysis, both LVMI and UAE were affected by NDS and MBP independent of other confounding variables (for LVMI; Coefficient =0.27, P=0.01 and Coefficient =0.37, P=0.001, respectively, and for UAE; Coefficient =0.27, P=0.02 and Coefficient =0.28, P=0.01, respectively). Conclusions: It may be postulated that increased night and MBP are the factors that cause TOD, and it seems reasonable to attempt to restore normal diurnal rhythm of the BP even in normotensive subjects. (Circ J 2009; 73: 899 - 904)

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Background: The purpose is to investigate the ability of 64-slice multidetector computed tomography (MDCT) at rest in detecting myocardial ischemia, conventionally depicted by myocardial perfusion scintigraphy (MPS). Methods and Results: In 75 patients with suspected coronary artery disease, cardiac CE-MDCT at rest and stress/rest MPS were performed. The 2D myocardial images were reconstructed in diastolic and systolic phases using raw data from coronary computed tomography (CT) angiography. CT numbers in the myocardium were used as an estimate of myocardial enhancement. The myocardium was shown using a color scale that depicts faint low-density areas more clearly than gray scale. The variation in myocardial enhancement was evaluated at systole and diastole for those segments depicted as ischemia on MPS. A pattern of transient endocardial hypo-enhancement at systole and normal enhancement at diastole as the ischemic pattern on CT myocardial image was defined. MPS diagnosed myocardial ischemia in 40 of 75 patients. Use of the ischemic pattern on CT images distinguished patients with and without ischemia with a sensitivity of 90%, specificity of 83%, positive predictive value of 86% and negative predictive value of 88%. Conclusions: CT myocardial imaging at rest demonstrates a characteristic enhancement pattern for ischemia. This has potential as a non-invasive method for detecting ischemia. (Circ J 2009; 73: 905 - 911)

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Background: Gender differences among patients with coronary artery disease vary from study to study. In one of the largest studies, the Japanese Coronary Artery Disease (JCAD) Study, gender differences in patients were investigated. Methods and Results: Consecutive patients diagnosed with stenosis 75% or more in at least one branch of the coronary arteries were enrolled in the study. The endpoint is a composite of all-cause death and cardiovascular events. Data were collected over the internet. Out of 15,628 patients screened, 13,812 of them met the inclusion criteria and were followed up for a mean period of 2.7 years. The event rate was 62.8 per 1,000 patients-year, all-cause death 17.3 and total cardiac events 47.4. The incident rate of unstable angina was higher in females (27.1) than males (21.8) (P=0.0363). The incidence of all-cause death was lower in females than males (16.9 and 17.8, respectively; P=0.0148). Other than gender, hypertension and number of vessel disease contribute to the event of unstable angina, and age, family history, obesity, impaired fasting glycemia, hyperlipidemia, congestive heart failure and number of vessel disease contribute to the all-cause death. Conclusions: Gender is an independent contributing factor of unstable angina and of all-cause death. (Circ J 2009; 73: 912 - 917)

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Background: Angiotensin-converting enzyme inhibitors (ACEI) reduce the mortality in the chronic phase of myocardial infarction (MI), and similar effects of angiotensin receptor blockers (ARB) have been reported. However, these effects of ARB have not yet been established in Japanese patients. A multicenter randomized study was designed for the present study to examine the effect of valsartan as compared to that of ACEI against left ventricular dysfunction after MI. Methods and Results: Patients with acute MI were randomly allocated to either the valsartan group (n=120; mean age 63 ±1.0) or the ACEI group (n=121; mean age 62.9 ±1.0) and followed up until 6 months. Left ventriculography was performed during hospital admission and at 6 months. The blood pressure was similar in the 2 groups throughout the study. The incidences of cardiovascular events and target vessel revascularization were similar, although that of adverse events was significantly higher in the ACEI (12.4%) than in the valsartan group (3.3%; P<0.05). There were no differences in left ventricular ejection fraction and left ventricular end-diastolic volume index between the groups. Conclusions: Valsartan exhibits similar efficacy effective to that of ACEI in preventing left ventricular dysfunction in Japanese patients with acute MI, and is, in addition, better tolerated than ACEI. (Circ J 2009; 73: 918 - 924)

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Background: It is controversial as to whether nicorandil would have cardioprotective effects in patients with acute myocardial infarction (AMI) who are undergoing reperfusion therapy. A meta-analysis was performed to study the impacts of nicorandil on functional outcomes after AMI. Methods and Results: Randomized prospective cohort or retrospective cohort publications were identified up to October 2007 by means of a computer search of MEDLINE and Google Scholar databases. Two reviewers checked the quality of the studies and extracted data regarding patient and disease characteristics, study design, functional parameters such as Thrombolysis In Myocardial Infarction (TIMI) flow grade after reperfusion, left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume index (LVEDVI). Seventeen studies were included for the meta-analysis in this study. Nicorandil treatment reduced the incidence of TIMI flow grade ≤2 in 1,337 patients of 10 studies (risk ratio 0.63; 95% confidence interval (CI) 0.44 to 0.91). While no beneficial effect was observed on the peak creatine kinase value, nicorandil treatment was associated with greater LVEF (by 3.7%, 95%CI 1.8 to 5.7%), and lower LVEDVI (by 8.8 ml/kg, -14.4 to -3.3 ml/kg) in 905 patients of 11 studies. Conclusions: The meta-analysis demonstrated that nicorandil treatment adjunctive to reperfusion therapy has beneficial effects on microvascular function and on functional recovery after AMI. (Circ J 2009; 73: 925 - 931)

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Background: Inflammatory processes in the atria during systemic inflammation remain unclear, so this study tested the hypothesis that macrophages infiltrate the atrial myocardium mainly through the atrial endocardium with the contribution of fractalkine. Methods and Results: Sprague-Dawley rats were injected with lipopolysaccharide (LPS) to simulate inflammation in the atria. Inflammation was immunohistologically assessed by the presence of macrophages. Macrophage infiltration was diffuse throughout the atrial myocardium after LPS injection. At an earlier phase after LPS injection, the number of macrophages dramatically increased, mainly in the atrial endocardium, and the expression of fractalkine protein was markedly increased by treatment with LPS in the atrial endocardium. The LPS-induced increase in atrial macrophage infiltration was significantly suppressed by neutralizing the fractalkine protein (P<0.01). Conclusions: In an experimental model of atrial inflammation, macrophages infiltrated the myocardium mainly through the atrial endocardium with the contribution of fractalkine. Inhibition of macrophage infiltration by suppressing chemokine expression could be a novel therapeutic approach to controling acute inflammation in the atria. (Circ J 2009; 73: 932 - 937)

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Background: Pulmonary sequestration (PS) is characterized by non-functioning lung tissue fed from 1 or several aberrant systemic arteries. The classical therapeutic approach is surgical resection. Several case reports have shown that coil embolization is feasible, but this technique has not been evaluated in a larger series of consecutively treated patients. The purpose of our study was to assess the early and long-term outcomes of coil embolization of PS in children and to determine the risk factors of early and late major adverse cardiovascular and pulmonary events. Methods and Results: Between March 1999 and December 2004, 6 patients (2 boys, 4 girls, mean age 4.7 ±3.8 years) with PS were treated by coil embolization of the feeding systemic artery. Four patients were considered to have been cured and 2 patients required a second coil embolization 6 months later because of residual systemic flow seen on computed tomography. Transient ischemic change of the lower limb occurred in the youngest patient. None of the other patients had any late complications or recurrent pneumonia. Conclusions: Coil embolization of PS is safe and feasible, with a good late outcome. (Circ J 2009; 73: 938 - 942)

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Background: Clinically useful indices of fetal cardiac function have not been fully delineated for tissue Doppler imaging (TDI). Methods and Results: In the present study, 56 pregnancies between the 17^th and 38^th weeks of gestation included 38 normal fetuses, 6 cases of hydrops fetalis (HF), and 12 of intrauterine growth retardation (IUGR). Peak velocity in early diastole (E) was measured by pulsed-wave Doppler and the peak annular velocities in systole (Sa) and early diastole (Ea) were measured by TDI. The ratio between flow velocity and annular velocity in early diastole (E/Ea) and the ratio of the Sa of right ventricle to that of the left ventricle (RVSa/LVSa) were estimated. In all fetuses with HF, LVSa was <2 cm/s and LVE/Ea was >13. RVSa/LVSa in the HF group was significantly higher than that in the normal group, and RVSa/LVSa in the IUGR group was significantly lower than that in the normal group. Conclusions: A combination of low LVSa and high LVE/Ea shows reduced global myocardial performance of the LV, and would be one of the useful indices for quantitative assessment in high-risk pregnancies. Changes in the RVSa/LVSa ratio may reflect afterload changes in both ventricles and compensatory cardiovascular mechanisms occurring during the process of placental insufficiency and heart failure. (Circ J 2009; 73: 943 - 947)

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Background: Peripheral arterial occlusion disease (PAOD) is caused mainly by chronic inflammation and endothelium dysfunction, and is often treated with cilostazol. However, because this drug's influence on atherogenic cytokines is still not well known, this study examined the effect of cilostazol on the serum levels of soluble CD40 ligand (sCD40L), adiponectin and high-sensitivity C-reactive protein (hs-CRP) in patients with type 2 diabetes and PAOD. Methods and Results: The 92 type 2 diabetics with PAOD and 100 non-PAOD diabetics were enrolled and randomly assigned to a group receiving either cilostazol or placebo for 6 months. The atherogenic cytokines were measured at the beginning and completion of the study. In the PAOD groups, those in the cilostazol group had significant changes in the levels of hs-CRP, sCD40L and adiponectin (P=0.001, P=0.05, P=0.004, respectively). Changes in the levels of adiponectin and sCD40L were more significant in the PAOD group treated with cilostazol than in the non-PAOD group also treated with the drug (P=0.01 and P=0.008, respectively). Conclusions: Cilostazol can decrease hs-CPR and sCD40L levels and increase that of adiponectin, and then delay the progression of atherogenesis and chronic inflammation in type 2 diabetics, especially those with PAOD. (Circ J 2009; 73: 948 - 954)

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Background: Although endothelium-dependent vasodilatation has been used as a marker of endothelial dysfunction (ED), there have been no reliable plasma markers for ED. Oxidative stress, which is a major determinant of ED, oxidizes tetrahydrobiopterin (BH4), an essential cofactor of endothelial type nitric oxide synthase (eNOS), and resulted in the relative deficiency of BH4. Methods and Results: In 163 patients with cardiovascular disorders, the plasma levels of BH4 and 7, 8-dihydrobiopterin (BH2) by high performance liquid chromatography were measured and compared with the flow-mediated (FMD) vasodilatory response of the brachial artery, which was measured by ultrasonography. The effects of atorvastatin on plasma pteridine levels and FMD were examined in patients with multiple coronary risk factors. There was a positive relationship between FMD and plasma BH4 levels and a negative relationship between FMD and plasma BH2 levels. Subsequently, a strong positive relationship between FMD and the BH4/BH2 ratio (r=0.585, P<0.0001) was found. Although we did not find any significant relationship between pteridine levels and individual traditional risk factors, the BH4/BH2 ratio in patients with more than 2 risk factors showed significant reductions compared with that in those without risk factors. Statin treatment improved FMD in association with an increase in the plasma BH4/BH2 ratio. Conclusions: Plasma pteridine levels were associated with endothelial dysfunction in cardiovascular disorders. (Circ J 2009; 73: 955 - 962)

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In 1982, a 49-year-old Japanese woman had been referred to our hospital for further investigation of her hypercholesterolemia. She was diagnosed as heterozygous familial hypercholesterolemia, because of Achilles tendon xanthoma and a family history of primary hypercholesterolemia. Three years later, she had chest pain on effort and angina pectoris was diagnosed by coronary angiography. At that time, she underwent coronary artery bypass grafting surgery with 2 saphenous vein grafts (SVG). Because more aggressive cholesterol-lowering therapy was needed for secondary prevention of coronary artery disease (CAD), weekly low-density lipoprotein (LDL) apheresis was started postoperatively, combined with drug therapy. Since 1986, her serum total cholesterol levels before and after LDL apheresis remained approximately 200 mg/dl and 90 mg/dl, respectively. Although her coronary sclerosis, including the SVG, did not progress appreciably for a period of 20 years, stenotic changes of the aortic valve developed rapidly at age 70, leading to aortic valve replacement surgery in 2005 at age 72. These findings suggest that careful attention to the progression of aortic valve stenosis is needed for extreme hypercholesterolemic patients even under optimal cholesterol-lowering therapy for the secondary prevention of CAD. (Circ J 2009; 73: 963 - 966)

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A 56-year-old man, suffering from rapidly worsening general fatigue, dyspnea on exercise and epigastralgia, was referred for evaluation and treatment of a cardiac tumor. Transthoracic echocardiography showed a 6-cm large mass occupying both the right ventricle and atrium. Gallium scintigraphy showed high uptake in the tumor site. Lymphoma was highly suggested. Urgent operation was performed and as much tumor and thrombus were removed as possible. The postoperative course was good, with cessation of right heart failure. Pathological examination suggested malignant lymphoma, diffuse large B-cell type. The patient was treated with rituximab, cyclophosphamide, Adriamycin, vincristine, and prednisone (CHOP-R) postoperatively and has survived for 2 years without signs of recurrence. (Circ J 2009; 73: 967 - 969)

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The progress of immunosuppressive therapy has made heart transplantation the standard therapy for end-stage heart failure. However, humoral rejection of the cardiac allograft is still a challenging problem associated with high incidence of graft loss and patient mortality. The present patient developed profound cardiogenic shock requiring extracorporeal life support on the 8th day after heart transplantation. Endomyocardial biopsy revealed no cellular rejection, and complement component C4d was positively stained on the capillary endothelium. The patient was successfully treated with repeated plasmapheresis and administration of anti-CD20 monoclonal antibody, rituximab, as well as with steroid pulse and increased standard immunosuppressive medication. (Circ J 2009; 73: 970 - 973)

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A 71 year-old man with a history of previous anterior myocardial infarction, triple coronary artery bypass graft and left ventricular (LV) aneurysmectomy was admitted to the cardiology unit for chest pain. Physical examination showed a pulsing mass in the left chest wall. Cardiac multislice computed tomography showed a rare case of LV pseudoaneurysm (6.3×6×10 cm) communicating by a fistulous trait (1 cm) with the left anterior chest wall (C7-C8), creating a subfascial mass (7.1×3.6 cm). (Circ J 2009; 73: 974 - 975)

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