Background On October 23, 2004, a major earthquake, which registered 6.8 on the Richter scale, occurred in Niigata Prefecture in Japan. Emotional stress is important as a trigger of transient left ventricular apical ballooning (so-called `Takotsubo' cardiomyopathy), but its incidence and clinical profile immediately after a natural disaster have not been fully elucidated. Methods and Results `Takotsubo' cardiomyopathy was diagnosed in 16 patients (1 man, 15 women, mean age 71.5 years) within 1 month after the earthquake. Of them, 13 (81%) lived in areas where the Japan Meteorological Agency seismic intensity scale registered 6 or above, and 11 (69%) developed symptoms on the day of the earthquake. The incidence of `Takotsubo' cardiomyopathy 1 month after the earthquake was approximately 24-fold higher near the epicenter than that before the earthquake. Conclusion `Takotsubo' cardiomyopathy can occur on the day of the earthquake in elderly women living near the epicenter. (Circ J 2006; 70: 947 - 953)

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Background Chronic kidney disease (CKD) has been identified as a risk factor for cardiovascular disease (CVD). Methods and Results The risk of cardiovascular death was evaluated in a large cohort of participants selected randomly from the overall Japanese population. Participants (mean age, 52.4 years) free of previous CVD were followed up for 10 years. Glomerular filtration rate (GFR) was estimated using the abbreviated equation developed at the Cleveland Clinic laboratory for the Modification of Diet in Renal Disease study. Of the 7,316 participants, 6.7% had CKD with a GFR <60 at baseline. Even after adjustment for other risk factors, the presence of CKD conferred an increased risk of cardiovascular death with a hazard ratio of 1.20 (95% confidence interval, 0.82-1.76). Furthermore, a negative, graded correlation between GFR and risk of cardiovascular death was observed: 1.09 (0.72-1.64) for a 60≤ GFR <90, 1.15 (0.67-1.99) for a 45≤ GFR <60, 1.23 (0.49-3.09) for a 30 ≤ GFR <45, 5.52 (1.62-18.75) for a 15≤ GFR <30, 9.12 (2.12-39.29) for a GFR <15, as compared with normal kidney function (GFR ≥90). The proportion of excess cardiovascular death due to CKD was 1.3%. Conclusion CKD was an independent risk factor for cardiovascular death in a community-dwelling Japanese population. (Circ J 2006; 70: 954 - 959)

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Background To examine the prognostic significance of the high-risk group with combined cardiovascular risk factors in the Japanese, we analyzed the relationship between the high-risk group with combined risks and coronary heart disease (CHD) and stroke mortality using the NIPPON DATA80 database. Methods and Results At baseline in 1980, those of age ≥30 years were randomly selected and 4,144 men and 5,318 women without CHD and/or stroke at baseline were followed for 14 years. The cutoff values for risk components obtained heuristically by Cox analysis were hypertension (systolic ≥130, or diastolic ≥85 mmHg, or on antihypertensive drugs), hypercholesterolemia (total cholesterol ≥200 mg/dl), hyperglycemia (≥130 mg/dl, or self-reported diabetes) and obesity (body mass index ≥27 kg/m²). Subjects were divided into 3 groups (0, 1-2 and 3-4 risks). Compared with those men in the risk 0 group, the hazard ratios in men in the risk 3-4 for CHD mortality was 8.04 (95% confidence interval: 1.03-62.6), and the stroke mortality was 5.06 (1.53-16.7). In women, no statistically significant difference was found due to a lesser number of events. Conclusion The high-risk group with combined risk factors is important risk for Japanese men. (Circ J 2006; 70: 960 - 964)

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Background The present study aimed to determine whether quality of life (QOL) in permanent atrial fibrillation (AF) patients would be improved by monotherapy with β-blocker (BB) or calcium antagonist (CAA) as compared with digitalis. Methods and Results Twenty-nine patients with permanent AF under digitalis were randomized into BB (bisoprolol, atenolol or metoprolol) or CAA (verapamil) monotherapy treatment group. Twenty-five were men and the mean age was 67±8 years. After the assigned monotherapy, 12 patients received the other monotherapy in a cross-over fashion. Under each treatment, efficacy of rate control was determined by Holter electrocardiogram (ECG), treadmill testing and QOL questionnaire (Short Form-36 (SF-36) and Quality of Life of Atrial Fibrillation (AFQLQ)), and compared with the baseline digitalis treatment. CAA significantly increased mean and minimum heart rate (HR) in Holter ECG as compared with digitalis, whereas BB increased only minimum HR. Exercise duration in treadmill testing was significantly prolonged by CAA treatment, although it only tended to be prolonged by BB treatment. CAA but not BB improved role function-physical score of SF-36, and frequency and severity of symptoms of AFQLQ. Conclusion These results indicate that CAA is preferable to digitalis when monotherapy is selected for short-term improvement of QOL and exercise tolerance in patients with permanent AF. (Circ J 2006; 70: 965 - 970)

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Background It is sometimes difficult to make a diagnosis of cardioembolic stroke in the stroke care unit, because of the splashing and vanishing of the intracardiac source of the emboli on transesophageal echocardiography. Serum fibrin-monomer (FM) is a new marker for coagulation activity that is useful for identifying older individuals at increased risk of ischemic stroke. Methods and Results Two hundred and four patients with acute ischemic stroke were examined for serum coagulation and fibrinolytic activity on admission, and underwent transesophageal echocardiography within 7 days of onset. Serum levels of FM was significantly higher in patients with left atrial appendage (LAA) thrombus formation (n=24) than in those with no thrombus (88±52 vs 14±9 μg/ml, p<0.0001). On multivariate logistic regression analysis, FM was an independent predictor for LAA thrombus (RR 2.975, 95% confidence interval 1.114 to 4.820, p=0.0214). In patients with LAA thrombus negative group, cases with LAA emptying flow velocity at atrial systole that was absent or smaller than at early diastole had significantly higher FM levels as compared to cases with larger velocity (42±12 vs 8±5 μg/ml, p<0.0001). Conclusion Higher levels of serum FM reflect LAA flow pattern alterations and thrombus formation in patients with acute ischemic stroke. (Circ J 2006; 70: 971 - 976)

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Background Whether amiodarone can improve the patient's clinical outcome by reducing implantable cardioverter-defibrillator (ICD) therapy deliveries for ventricular tachycardia or fibrillation (VT/VF) has not been clearly evaluated. Methods and Results A total of 507 patients with VT/VF due to organic heart disease who had ICDs implanted were enrolled in this study. The patients were divided into 3 groups: Amiodarone (n=247), Class I anti-arrhythmic drug (n=103) and Control (n=157) groups, and the total cause mortality and arrhythmic event free survival rates were evaluated between the groups. The mean follow-up period was 38±27 months. The left ventricular ejection fraction was significantly decreased in the Amiodarone group (Amiodarone: 37±15%; Class I: 39±16%; Control: 44±17%). The mortality and arrhythmic events were significantly higher in the Class I group than the Amiodarone group (p<0.05), but there was no significant difference between the Amiodarone and Control groups (arrhythmic event free rate at 5 years: Amiodarone: 53%; Class I: 35%; Control: 48%; 5 year survival: 86%, 74% and 77%, respectively). Side effects from amiodarone were found in 12% of the patients, but no fatal events were observed. Conclusions The present study could not demonstrate the benefit of amiodarone in ICD patients, probably due to a significant clinical bias exerted in selecting this drug. (Circ J 2006; 70: 977 - 984)

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Background The cause of abnormally low amplitude of the initial P wave signal-averaged electrocardiogram (P-SAECG) in patients with sick sinus syndrome (SSS) is unknown. Methods and Results Thirteen normal patients (Group C) and 33 with SSS (Group S) were examined. The root mean square amplitude for the initial 30 ms (EP30) and the duration of below-4 μV signals of the filtered P waves (ED4) were measured using the P-SAECG. The interval from an atrial potential on the sinus-node electrogram (SNE) to P wave onset (AS-P), and the interval from the P wave to the atrial potential on the His-bundle-electrogram (P-AH) were measured in the electrophysiological study. The sino-atrial conduction time was measured by a conventional method (indirect sino-atrial conduction time (SACTi)) and using SNE (direct sino-atrial conduction time (SACTd)). The EP30 was significantly lower and the ED4 significantly longer in Group S. The AS-P was significantly longer in Group S (p<0.01), but the P-AH was not different. In Group S, the AS-P was significantly correlated with EP30 and ED4 (p<0.01), but the P-AH was uncorrelated. The SACTi was significantly correlated with EP30 and ED4 (p<0.05), but the SACTd was uncorrelated. Conclusion The abnormality of the initial portion of the P-SAECG observed in SSS appears to be due to disturbed conduction through the atrial myocardium around the sino-atrial node. (Circ J 2006; 70: 985 - 990)

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Background In muscular dystrophy, cardiac function deteriorates with time and heart failure is one of the major causes of death. Although the combination of angiotensin-converting enzyme inhibitors (ACEI) and β-blockers improves cardiac function in adults, little is known about the efficacy of those drugs in patients with muscular dystrophy. Methods and Results The effect of the β-blocker, carvedilol, and/or ACEI on ventricular function in patients with muscular dystrophy was studied. Carvedilol and an ACEI were given to 13 patients (ACEI group; mean age 18 years, range 7-27 years), and an ACEI only to 15 patients (carvedilol group; mean age 15 years, range 8-29 years). Diagnoses included Duchenne muscular dystrophy (n=25), Fukuyama muscular dystrophy (n=2), and Emery-Dreifuss muscular dystrophy (n=1). Echocardiographic parameters of the left ventricle were measured during the 2-3 years of follow-up. In the carvedilol group, combination therapy of carvedilol and an ACEI for 2 years resulted in a significant increase in left ventricular fractional shortening (LVFS). In the ACEI group, there was no significant change in LVFS. Left ventricular end-diastolic dimension increased in the ACEI group, but not in the carvedilol group. Conclusion Carvedilol plus an ACEI improves left ventricular systolic function in patients with muscular dystrophy. (Circ J 2006; 70: 991 - 994)

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Background Angiotensin II receptor blockers (ARB) are now commonly used to treat hypertension because of their beneficial effects on cardiovascular remodeling. However, ARB treatment can not inhibit the left ventricular (LV) remodeling sufficiently, which may be related with aldosterone secretion. To inhibit the action of aldosterone during ARB treatment, the additional effects of an aldosterone blocker and spironolactone (SPRL) on LV hypertrophy in patients with essential hypertension was studied. Methods and Results The patients with essential hypertension were randomly divided into 2 groups; 1 group was treated with an ARB, candesartan (8 mg/day), for 1 year (ARB group) and other group was treated with the ARB for the first 6 months and with the ARB plus SPRL (25 mg/day) for the next 6 months (combination group). Seventy patients who underwent echocardiography every 6 months were analyzed and were also classified into 4 subgroups of LV geometric pattern according to the LV mass index (LVMI) and the relative wall thickness (RWT). The ARB treatment and the addition of SPRL significantly reduced the blood pressure, however, both treatments did not affect the LV geometry in both groups. The ARB treatment in the subgroups of concentric LV remodeling (RWT ≥0.45 and LVMI <125) and concentric LV hypertrophy (RWT ≥0.45 and LVMI ≥125) significantly reduced RWT. However, ARB treatment in all subgroups did not affect LVMI. The addition of SPRL only in the concentric LV hypertrophy subgroup significantly reduced the LVMI, despite similar changes in blood pressure. Conclusions These results indicated that the addition of SPRL treatment during the ARB treatment and conventional treatments is clinically useful to reduce the LVMI in hypertensive patients with concentric LV hypertrophy; however, does not improve the eccentric LV hypertrophy. (Circ J 2006; 70: 995 - 1000)

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Background Oxidative stress has been implicated in the pathogenesis of chronic heart failure. The present study investigated whether the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, were elevated in the serum and myocardium of patients with dilated cardiomyopathy (DCM), and furthermore whether carvedilol, a vasodilating β-blocker with antioxidant activity, could reduce the levels. Methods and Results Serum levels of 8-OHdG were measured by enzyme immunoassay in 56 patients with DCM and in 20 control subjects. DCM patients had significantly elevated serum levels of 8-OHdG compared with control subjects. Endomyocardial biopsy samples obtained from 12 DCM patients and 5 control subjects with normal cardiac function were studied immunohistochemically for the expression of 8-OHdG. Positive 8-OHdG staining was found in the nuclei of cardiomyocytes from DCM patients but not in those from control subjects. After treatment with carvedilol, the serum levels of 8-OHdG in DCM patients significantly decreased by 19%, together with amelioration of heart failure. Conclusions Levels of 8-OHdG are elevated in the serum and myocardium of patients with heart failure. Treatment with carvedilol might be effective for decreasing the oxidative DNA damage. (Circ J 2006; 70: 1001 - 1005)

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Background A recent study suggested that xanthine oxidase is activated in congestive heart failure (CHF). However, whether uric acid (UA) is secreted from the failing heart remains unknown, so it is currently unclear whether serum UA can provide prognostic information independent of brain natriuretic peptide (BNP). Methods and Results Serum UA was measured in the aortic root (AO) and the coronary sinus (CS) of 74 patients with CHF. The serum UA level was significantly higher in the CS than in the AO. The transcardiac gradient of UA (CS - AO) increased with the severity of CHF, inversely correlated with left ventricular ejection fraction (LVEF) and positively correlated with left ventricular end-diastolic volume index. The plasma levels of norepinephrine, BNP, UA, and LVEF were monitored prospectively in 150 CHF patients for a mean follow-up of 3 years. High plasma levels of UA (p<0.001) and BNP (p<0.001) were shown by multivariate stepwise analysis to be independent predictors of mortality. Conclusions High plasma UA level, partly secreted from the failing heart, is a prognostic predictor independent of BNP in patients with CHF. Monitoring a combination of BNP and UA may be useful for the management of patients with CHF. (Circ J 2006; 70: 1006 - 1011)

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Background Stable coronary artery disease (CAD) is classified into 2 types: high-risk (ie, 3-vessel disease, left main trunk lesions, or ostial lesions of the left anterior descending (LAD)) and low-risk (1- or 2-vessel disease other than ostial lesions of the LAD). Generally, the former is treated with coronary artery bypass grafting-preceding therapy (CABG), but not medical-preceding therapy (Medical); however, this is based on evidence from 30 years ago or more and does not reflect the recent progression of Medical and CABG. In addition, a randomized study has not been performed in Japan. Methods and Results In high-risk CAD, the long-term outcomes of 77 Medical patients and age-, sex-, coronary-lesion-, symptom- and risk-factor-matched 99 CABG patients were surveyed over 3 years (mean: 3.4 years) starting in 2000 at 37 nationwide hospitals. The incidences of cardiac death and cardiac death + non-fatal acute coronary syndrome (9.1% and 11.7% in Medical, and 2.0% and 3.0% in CABG, respectively) were significantly higher and the improvement in clinical symptoms was significantly lower in Medical than CABG. Conclusions CABG is recommended in patients with high-risk CAD from the view of long-term prognosis; however, it should be remembered that the long-term outcome in Medical has considerably improved. (Circ J 2006; 70: 1012 - 1016)

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Background The aim of this study was to clarify the influence of sympathetic and parasympathetic nerve (SN and PN) dysfunction on the heart rate (HR) response to exercise and the exercise capacity of patients with acute myocardial infarction (AMI) and diabetes mellitus (DM). Methods and Results Fifty-two male patients who underwent cardiopulmonary exercise testing (CPX) 1 month after onset of AMI were divided into 2 groups: (DM (+) group, n=20; DM (-) group, n=32). HR, peak oxygen uptake (VO_2peak), and plasma norepinephrine (NE) levels were measured during CPX. The high-frequency power (HF) was analyzed by HR variability. The ΔHR/log ΔNE obtained from changes of HR and NE from rest to peak exercise and HR change from baseline to the minimum HF (ΔHR_HF) were calculated as parameters of HR response derived from SN and PN activities, respectively. ΔHR, VO_2peak, ΔHR/log ΔNE, and ΔHR_HF were significantly lower in the DM (+) group than in the DM (-) group, and both of them showed positive correlations with VO_2peak. Conclusion An inadequate HR response to exercise is a major factor causing a decline of exercise capacity, which is derived from both of SN and PN dysfunction, in AMI patients with DM. (Circ J 2006; 70: 1017 - 1025)

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Background In-stent restenosis is considered to be a gradual and progressive condition and there is scant data on myocardial infarction (MI) as a clinical presentation. Methods and Results Of 2,462 consecutive patients who underwent percutaneous coronary intervention between June 2001 and December 2002, clinical in-stent restenosis occurred in 212 (8.6%), who were classified into 3 groups: ST elevation MI (STEMI), non-ST elevation MI (NSTEMI) and non-MI. Of the 212 patients presenting with clinical in-stent restenosis, 22 (10.4%) had MI (creatine kinase (CK) ≥2 × baseline with elevated CKMB). The remaining 190 (89.6%) patients had stable angina or evidence of ischemia by stress test without elevation of cardiac enzymes. Median interval between previous intervention and presentation for clinical in-stent restenosis was shorter for patients with MI than for non-MI patients (STEMI, 90 days; NSTEMI, 79 days; non-MI, 125 days; p=0.07). Diffuse in-stent restenosis was more frequent in MI patients than in non-MI patients (72.7% vs 56.3%; p<0.005). Renal failure was more prevalent in patients with MI than in those without MI (31.8% vs 6.3%, p=0.001). Compared with the non-MI group, patients with MI were more likely to have acute coronary syndromes at the time of index procedure (81.8% vs 56.8%, p=0.02). Conclusion Clinical in-stent restenosis can frequently present as MI and such patients are more likely to have an aggressive angiographic pattern of restenosis. Renal failure and acute coronary syndromes at the initial procedure are associated with MI. (Circ J 2006; 70: 1026 - 1029)

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Background Hypertriglyceridemia (HTG) is a heterogeneous metabolic disorder. The aim of this study was to examine associations among genetic polymorphisms, SstI polymorphism of apolipoprotein CIII (ApoCIII) and Hind III polymorphism of lipoprotein lipase (LPL), environmental factors and risks of HTG. Methods and Results Two hundred and forty-nine southern Taiwanese aborigines were recruited for a cross-sectional study, which included 90 subjects with triglyceride (TG) >150 mg/dl (HTG) and 159 with TG ≤150 mg/dl (NTG). The frequencies of SstI major allele (S1) and minor allele (S2) of ApoCIII were 66.1% and 33.9% in HTG and 73.6% and 26.4% in NTG (p<0.1). In female subjects, the frequencies of the S2 allele was significantly higher in HTG (0.38) than NTG (0.27) (p<0.04). The frequencies of the LPL HindIII major allele (H+) and minor allele (H-) were similar between HTG (H+ 84.3%; H- 15.7%) and NTG (H+ 78.9%; H- 21.1%). In a multivariate adjusted logistic model, education ≤6 year (odds ratio (OR) =3.71, 95% confidence interval (CI): 1.24-8.13), Amis tribe (OR =3.08, 95% CI: 1.41-6.77), body mass index (BMI) ≥25 (OR =2.22, 95% CI: 1.18-4.16), starchy food consumption ≥3 times/week (OR =1.89, 95% CI: 1.00-3.59) and ApoCIII S2S2 genotype (OR =3.35, 95% CI: 1.10-10.19) were independently (p<0.05) associated with HTG risks. Among ApoCIII S1S1, S1S2 and S2S2 genotypes, ApoCIII and TG concentrations increased (p<0.01) in a dose-responsive manner. Conclusions The ApoCIII S2 variant and environmental factors, including education, tribal background, BMI and starchy food intake, modulate the risks of HTG in aboriginal Taiwanese. Interaction between genetic and environmental factors warrants further investigation. (Circ J 2006; 70: 1030 - 1036)

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Background The present study evaluated the prognostic significance of Doppler-demonstrated left ventricular (LV) restrictive filling pattern (RFP) in patients with thalassaemia major (TM), which carries an adverse cardiovascular prognosis. Methods and Results The study group comprised 45 asymptomatic transfusion-dependent patients with TM and normal LV systolic function. All patients were chelated with desferrioxamine. They were regularly evaluated by clinical and Doppler-echocardiographic studies throughout the 15-year follow-up period. The patients were categorized into 2 groups according to baseline data: those with LVRFP and those with LV non-RFP. The incidence of cardiac death in both groups was analyzed. The impact of chelation therapy on the ventricular filling pattern and survival was also examined. Nineteen patients (42.2%) had LVRFP and 26 (57.8%) had LV non-RFP. During follow-up 11 patients died from cardiac causes; 8 of them (72.8%) initially had LVRFP and 3 (27.2%) had LV non-RFP. LVRFP was significantly associated with mortality (p=0.018). Poor compliance with chelation therapy was significantly associated with LVRFP (p=0.007) and cardiac mortality (p=0.003). Conclusions LVRFP is an important predictor of cardiac mortality in patients with TM. Poor compliance with chelation therapy was significantly associated with both a RFP (p=0.007) and cardiac mortality (p=0.003). (Circ J 2006; 70: 1037 - 1042)

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Background Ruptured sinus of Valsalva aneurysms (RSVA) can be associated with ventricular septal defects or isolated lesions. Surgical repair has been the traditional treatment of for the RSVA. The results of transcatheter closure of the RSVA in 4 patients are reported. Methods and Results From 2003 to 2004, 4 patients (2 males and 2 females) aged from 18 years to 47 years with RSVA were identified. The diagnosis of RSVA was made based on a combination of several imaging modalities. The drainage site of the RSVA was right ventricle in 2, and right atrium in remaining 2. All patients underwent general anesthesia and transesophageal echocardiographic (TEE) monitoring during the procedure. Transcatheter closure with an Amplatzer duct occluder was attempted in all 4 patients. The size of the Amplatzer duct occluder selected was up to 2 mm larger than the maximal diameter of the aortic opening site of the RSVA as measured on TEE images. The attempt to deploy an Amplatzer duct occluder was successful in 3 and a Gianturco coil was deployed in 1. Follow-up (3-18 months) echocardiography showed neither residual shunt nor aortic regurgitation in any of the patients. Conclusion The transcatheter technique is a safe alternative in the treatment of RSVA; however, a longer follow-up is mandatory. (Circ J 2006; 70: 1043 - 1047)

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Background The effectiveness and advantages of off-pump coronary artery bypass (OPCAB) for patients with concomitant malignant neoplastic disorders were analyzed. Methods and Results The study group comprised 368 patients who underwent OPCAB and of them 18 had concomitant malignant neoplastic disease: 14 with solitary malignant disease, 4 with low-grade lymphocytic malignancies. The age of the patients ranged from 49 to 72 years (mean 61). The mean left ventricular ejection fraction was 46.4% (range: 35-60%) and the mean number of grafts was 2.4±0.9. The left internal mammary artery was used in 12 patients (75%). Mean blood loss was 420±64 ml and the average requirement for blood transfusion was 1.1±0.2 units. There was no postoperative infection or in-hospital mortality. The mean length of hospital stay was 6.4±1.3 days. Mid-term follow-up was completed (100%) and the mean follow-up period was 22.6±4.1 months. All patients with a solitary malignancy underwent subsequent non-cardiac surgery with a mean interval of 16.4±3.3 days. Mid-term survival was 83.4%. Freedom from late cardiac events (angina, myocardial infarction, percutaneous transluminal coronary angioplasty) that required hospital admission was 92.3%. Conclusion These results support the effectiveness of OPCAB, mostly as a bridge to safe non-cardiac surgery that can be crucial for long-term survival. (Circ J 2006; 70: 1048 - 1051)

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Background The present study was designed to investigate the effect and relationship of endothelial function and endothelial progenitor cells (EPCs) by green tea consumption in chronic smokers. The numbers of circulating EPCs have an inverse correlation with chronic smoking and endothelial dysfunction. Green tea catechin improved endothelial dysfunction in chronic smokers. Method and Results In 20 young healthy smokers, endothelial functions, defined by flow-mediated endothelium dependent vasodilation (FMD) of the brachial artery via ultrasound as well as the number of EPCs isolated from peripheral blood, were determined at baseline and at 2 weeks after green tea consumption (8 g/day). Circulating EPCs were quantified by flow cytometry as CD45lowCD34 + KDR2+ cells and by acyl-low-density lipoprotein and fluorescein isotiocyanate-lectin double positive cells after culture for 7 days. Clinical characteristics and laboratory findings were not significantly different between the baseline and at 2 weeks after green tea intake. EPC levels were inversely correlated with the number of cigarettes smoked. Circulating EPCs by flow cytometry (78.6 ±72.6 vs 156.1±135.8 /ml, p<0.001) and cultured EPCs (118.2±35.7 vs 169.31±58.3/10 field, p<0.001) increased rapidly at 2 weeks after green tea consumption. FMD was significantly improved after 2 weeks (7.2±2.8 vs 9.3±2.4, p<0.001). The FMD correlated with EPC counts (r=0.67, p=0.003) before treatment and after 2 weeks (r=0.60, p=0.013). Conclusions A short-term administration of green tea consumption induces a rapid improvement of EPC levels and FMD. Green tea consumption may be effective to prevent future cardiovascular events in chronic smokers. (Circ J 2006; 70: 1052 -1057)

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Background In non-thromboembolic pulmonary hypertension, endothelin (ET)-1 levels are increased and correlate with the hemodynamic severity of the disease. Whether such correlations exist in chronic thromboembolic pulmonary hypertension (CTEPH) is unknown, nor whether ET-1 levels correlate with hemodynamic outcome after pulmonary endarterectomy (PEA). Methods and Results ET-1 levels were determined by ELISA. ET-levels were increased in 35 CTEPH patients (1.62±0.21 pg/ml) compared with healthy controls (n=11: 0.75±0.06 pg/ml, p<0.02). ET-1 levels correlated (all p<0.0001) with mean pulmonary artery pressure (mPAP) (r=0.70), cardiac index (r=-0.76), total pulmonary resistance (r=0.72), mixed venous oxygen saturation (r=-0.87), and the distance walked in the 6-min walk test (r=-0.59; p<0.005; n=23). Three months after PEA, ET-1 levels had decreased (p<0.002), and were similar between patients with and without residual pulmonary hypertension (p=0.4). Preoperative ET-1 levels, however, were higher in patients with bad postoperative outcome; that is, patients who either died because of persistent pulmonary hypertension or had residual pulmonary hypertension after PEA (2.68±0.48 pg/ml, and 1.13±0.15 pg/ml, respectively; p<0.002). The levels also correlated with hemodynamic outcome after PEA (mPAP: r=0.67, p<0.0001). By receiver-operator characteristic curve analysis, ET-1 >1.77 pg/ml detected a bad postoperative outcome with a sensitivity and specificity of 79% and 85%, respectively, and a likelihood ratio of 5.2. Conclusion ET-1 levels in CTEPH closely correlated with the hemodynamic and clinical severity of disease in a large cohort of patients. Preoperative ET-1 levels may be useful for better identification of patients at risk for persistent pulmonary hypertension after PEA. (Circ J 2006; 70: 1058 - 1063)

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Background Although an elevated blood glucose has prognostic value in cardiovascular disease, few data are available regarding its prognostic value for patients across the spectrum of cardiogenic shock. Method and Results A total of 81 patients with cardiogenic shock whose blood glucose and adrenaline were measured on arrival at the emergency room (ER) were enrolled in this prospective study. The primary endpoint was death from any cause in hospital. The rate of death was 12.3% (10/81), and the glucose level was lower among patients who were discharged alive than among those who died (8.7±3.7 mmol/L vs 13.8±6.7 mmol/L, p<0.001). The unadjusted rate of death increased in a stepwise fashion among patients in increasing quartiles of glucose level (p<0.05). The blood glucose level of 9.2 mmol/L had the highest combined sensitivity and specificity for the identification of death. In the multiple logistic-regression analysis for the primary outcome, the adjusted odd ratio for a glucose level of 9.2 mmol/L or more was 5.8 (95% confidence interval, 1.0-32.8, p=0.047). There was a significant positive correlation between the glucose and adrenaline levels (R=0.726, p<0.0001). Conclusion The measurement of blood glucose level on ER arrival provides predictive information for use in risk stratification across the spectrum of cardiac emergencies complicated by cardiogenic shock. (Circ J 2006; 70: 1064 - 1069)

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Background Ischemic preconditioning (IPC) produces immediate tolerance to subsequent prolonged ischemia/reperfusion (I/R), although the underlying mechanism remains unknown. The purpose of this study was to examine the role of nitric oxide (NO) and protein kinase C (PKC) in IPC-attenuated post ischemic leukocyte - endothelium interactions. Methods and Results Male Sprague-Dawley rats were randomized (n=8 per group) into 5 groups: sham-operated control group, IPC group, I/R group (4 h of pubic epigastric artery ischemia followed by 2 h of reperfusion), IPC + I/R group (30 min of ischemia followed by 30 min of reperfusion before I/R), and chelerythrine (PKC inhibitor) + IPC + I/R group. Intravital microscopy was used to observe leukocyte - endothelium interaction and to quantify functional capillaries in rat cremaster muscle flaps. The mRNA expressions of neuronal (n) NO synthase (NOS), inducible (i) NOS, and endothelial (e) NOS were determined by reverse transcription-polymerase chain reaction. The results showed that besides increasing functional capillary density, IPC also prevents I/R-induced increases in leukocyte rolling, adhesion, and migration. In the chelerythrine + IPC + I/R group, the IPC protective action was inhibited by the addition of chelerythrine. It was also observed that IPC upregulated nNOS, iNOS, and eNOS mRNA in I/R injured tissue, but this effect was not blocked by chelerythrine. Furthermore, specifically pretreated nNOS and iNOS inhibitors, along with a nonselective NOS inhibitor, were used in the IPC + I/R group to examine their possible antagonistic effects on leukocyte - endothelium interactions. Inhibition of the nNOS and iNOS activities did not block the beneficial effects of IPC. In contrast, pretreatment with the nonselective NOS inhibitor (N^G-nitro-L-arginine methylester) in the IPC + I/R group almost completely blocked the protective effect of IPC. Conclusions Both NOS and PKC play a protective role during IPC, but probably in distinct ways. Furthermore, the results also indicate that eNOS, but not nNOS nor iNOS, is the key mediator of IPC-attenuated I/R-induced microcirculatory disturbance. (Circ J 2006; 70: 1070 - 1075)

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Background Both the number and function of bone marrow-derived endothelial progenitor cells (EPCs) have been shown to be impaired in patients with diabetes mellitus. Therefore, we investigated the effect of glucose on the senescence of EPCs. Methods and Results EPCs were isolated from human peripheral blood and characterized to evaluate the effect of glucose (in 5-12.5 mmol/L) on the rate of senescence by acidic β-galactosidase staining. The phosphorylation of p38 mitogen-activated protein kinase (MAPK) level was analyzed by ELISA. The exposure of cultured EPC to high glucose (HG; 12.5 mmol/L) significantly accelerated the rate of senescence compared with that in osmolar control (L-glucose) during 10 days culture. An inhibitory effect of HG on EPC proliferation disclosed by an MTS assay. The phosphorylation of p38 MAPK in EPCs was also increased by glucose compared with control in a dose-dependent manner. HG-induced EPC senescence was significantly inhibited by the addition of an inhibitor of the p38 MAPK, SB203580. Conclusions HG accelerates the onset of EPCs senescence leading to the impairment of proliferative activity, which might be related to the phosphorylation of p38 MAPK. (Circ J 2006; 70: 1076 - 1081)

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Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are autoimmune inflammatory diseases associated with juvenile atherosclerosis and thrombosis, respectively. A 44-year-old woman who had SLE with secondary APS had been treated with corticosteroid therapy, however, her inflammatory marker had never been within a normal range in her clinical course, and finally acute myocardial infarction was developed. Intra-vascular ultrasound also revealed diffuse coronary atherosclerosis progression for her age, which might result from SLE and APS, including vascular inflammation. (Circ J 2006; 70: 1082 - 1085)

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Most patients with acute myocarditis manifest particular clinical signs and symptoms, including marked cardiac failure and/or a high degree of atrioventricular block on admission. However, a 78-year-old man did not have symptoms and was hospitalized as a result of abnormalities observed on an incidentally obtained electrocardiogram (ECG). Several days later, he developed cardiogenic shock and fulminant myocarditis, which required percutaneous cardiopulmonary support; however, the cardiac failure persisted and he died approximately 4 months later. The ECG showed findings similar to those of acute inferior myocardial infarction, and on left ventriculography, diffuse hypokinesis was observed most prominently in the inferoposterior wall. During autopsy, interstitial fibrosis was marked in the inferoposterior wall, with small, round, cell infiltration prominent at the same site. Clustering of these cells is a characteristic feature of chronic myocarditis. (Circ J 2006; 70: 1086 - 1090)

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Background The incidence of subacute stent thrombosis (SAT) within 30 days after stenting with a sirolimus-eluting stent (Cypher^®) for acute myocardial infarction (AMI) was retrospectively compared to that with bare-metal stents (BMS). Methods and Results Among 559 lesions in 558 consecutive AMI from April 2003 to February 2006, the incidence of documented SAT after Cypher^® implantation (2/276 lesions, 0.72%) was almost the same as for BMS (2 cases, 0.71%). Aspirin (81-100 mg/day) plus ticlopidine (200 mg/day) were administered continuously after admission in all 4 cases. Conclusion Documented SAT did not increase after stenting with Cypher ^® for AMI under aspirin plus ticlopidine. (Circ J 2006; 70: 1091 - 1092)

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