Background The relationship of admission neutrophil count to the degree of microvascular injury, left ventricular (LV) volume, and long-term outcome after acute myocardial infarction (AMI) was examined in the present study. Methods and Results The study group comprised 228 consecutive patients with a first anterior wall AMI who underwent primary angioplasty within 12 h of onset. The degree of microvascular injury was evaluated by Doppler guidewire. Adverse cardiac events were recorded during an average follow-up of 52±28 months. Using a receiver-operating characteristic analysis, a neutrophil count ≥7,260 cells/mm³ was the best predictor of future cardiac events. By regression analysis, the neutrophil count significantly correlated with diastolic deceleration time (r=-0.40, p<0.0001), coronary flow reserve (r=-0.43, p<0.0001), and LV end-diastolic volume at 4 weeks (r=0.32, p<0.0001). Kaplan-Meier survival analysis showed a higher incidence of adverse cardiac events in patients with a high neutrophil count (p=0.002). By multivariate analysis, a neutrophil count ≥7,260 cells/mm³ was an independent predictor of long-term adverse cardiac events (odds ratio 3.8, p=0.002). Conclusion Neutrophilia on admission is associated with impaired microvascular perfusion, LV dilation, and long-term adverse cardiac events in patients treated with primary angioplasty for AMI. (Circ J 2008; 72: 867 - 872)

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Background Although ischemia induced QRS complex changes have been described previously, their relationship with impaired reperfusion, which is known to be associated with poor clinical outcomes, is not clear. Methods and Results To investigate the relationship of QRS duration changes with myocardial reperfusion, we studied 165 acute myocardial infarction (MI) patients who were administered fibrinolytic therapy for reperfusion. For each patient, 12-lead electrocardiogram (ECG) with a paper speed of 50 mm/s was recorded on admission and repeated at the 60^th and 90^th min following fibrinolytic therapy. Based on the myocardial blush grades obtained from a control coronary angiography, patients were divided into reperfusion (grades 2, 3) and impaired reperfusion (grades 0, 1) groups. We detected impaired reperfusion in 74 patients. The patients in the impaired reperfusion group were older, more often diabetic, and had longer pain-to-needle intervals. They also had significantly longer QRS durations at admission compared to reperfusion group patients (91±11 vs 79±11 ms, p<0.001). Reperfusion group patients showed significantly greater resolution in QRS duration at the 90^th min post fibrinolysis ECG (18±5 vs 5±4 ms, p<0.001). In regression analysis, the pain-to-needle time (odds ratio (OR): 0.55, 95% confidence interval (CI) 0.35-0.88, p=0.012), QRS duration on admission (OR: 0.80, 95% CI 0.67-0.97, p=0.021), and change in QRS duration at the post fibrinolysis 90^th min ECG (OR: 2.43, 95% CI, 1.29-4.60, p=0.006) were determined as independent predictors of adequate reperfusion. Conclusion The present study, for the first time, has shown that admission QRS duration and post fibrinolysis 90^th min QRS duration changes are related to tissue reperfusion in fibrinolytic administered acute MI patients. (Circ J 2008; 72: 873 - 879)

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Background Although ostial lesion (defined as being within 3 mm of the ostia) of the right coronary artery (RCAos) has been a limitation of percutaneous coronary intervention after using previous various devices, the angiographic and clinical outcomes after the deployment of a sirolimus-eluting stent (SES) to RCAos have not been fully estimated. Therefore, the incidences of binary restenosis (BR; % diameter stenosis at chronic phase ≤50) and target lesion revascularization (TLR) after SES to RCAos were retrospectively compared with those after SES to RCA proximal (RCApro) and those after bare metal stents (BMS) to RCAos. Methods and Results The ratios of BR (18.9%) and TLR (13.5%) after SES to RCAos (n=37, mean follow-up interval of each group was 249 days) were significantly decreased compared with those of BMS to RCAos (41.7%, 36.1%, p<0.01, respectively) (n=36, 194 days), but were significantly increased compared with those of SES to RCApro (4.84%, 1.61%, p<0.01, respectively) (n=62, 240 days). There were no incidences of death, myocardial infarction, and definite stent thrombosis during the observational intervals in the entire cohort of 125 patients. Conclusions RCAos has to be taken into consideration as one of the limitations of SES because of the marked increase in the incident ratios of BR and TLR compared with those of RCApro, although SES demonstrated a likewise benefit compared with BMS. (Circ J 2008; 72: 880 - 885)

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Background Final kissing balloon technique (KBT) is known to alter long-term clinical outcomes for treatment of bifurcated coronary lesions. However, determination of adequate diameters of the 2 balloons remains difficult because of lack of a working index. Methods and Results Twenty-one cases of left main (LM)-related bifurcated lesions, treated with Cypher^TM stents (single/crush stenting) and final KBT, were enrolled. The formula "R² = D₁² + D₂²" was used, adjusting balloon diameter (D₁, D₂) to the downstream branches, to predict the theoretical mean hugging balloon diameter (R) within the main portion. The degree and pattern of stent expansion in the LM and main branch (MB) segments was compared by volumetric intravascular ultrasound assessment. Stents in the LM segments expanded to a greater extent and more asymmetrically than in MB segments (average stent area: 13.2±3.1 mm² vs 7.6±2.1 mm², p<0.0001, stent symmetry index: 0.77±0.08 vs 0.88±0.03, p<0.0001). The actual mean stent diameter significantly correlated with R (p=0.0003, r=0.76). The ratio of actual to theoretical stent expansion was highly consistent between the LM and MB (93.1% vs 93.4%, p=NS). Conclusion The proposed formula may be useful for predicting resultant stent expansion following KBT, despite a more elliptical dilation. (Circ J 2008; 72: 886 - 892)

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Background Metallic allergy is associated with restenosis following bare metal stent implantation, but the impact of metallic allergy on the outcome after implantation of drug-eluting stents (DES) has not been investigated. Methods and Results The present study group consisted of 88 consecutive patients (109 lesions) who underwent percutaneous coronary intervention with sirolimus-eluting stents (SES). Follow-up angiography was obtained at 8 months in all patients. At that time, the patients underwent epicutaneous patch tests for nickel, chromate, molybdenum, manganese, and titanium, which were evaluated after 48 h of contact. The patch test was positive in 14 patients (16%) (5 for manganese, 3 for nickel, 1 for chromate, 1 for Nickel and manganese, and 4 for manganese and chromate). The binary restenosis rate in the patients with a positive patch test was similar to those with negative patch test (6.3% vs 6.5%, p=0.98). Serial quantitative coronary angiography analyses identified no significant differences in late lumen loss of in-stent segments between patients with positive patch test and those with negative patch test (0.19±0.49 mm vs 0.12±0.48 mm, p=0.55). Conclusion SES prevent restenosis irrespective of metallic allergy. The classic relationship between metallic allergy and in-stent restenosis, seen with bare metal stents, does not appear to arise with DES, possibly because of the immunosuppressive effect of sirolimus. (Circ J 2008; 72: 893 - 896)

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Background The aims of the present study were to explore the mobilization of bone marrow-derived CD34⁺/133⁺ cells in patients with acute myocardial infarction (AMI) and bare metal stent implantation who participated in daily exercise training, and associations with exercise capacity and restenosis. Methods and Results Participants comprised 23 Japanese men with AMI (Killip 1) who had been treated with a bare metal stent. All patients were advised to walk for 30-60 min/day, at least 4 times per week starting at 11 days after AMI, and were instructed to record the amount of time spent walking each day. At 10 days and then at 3 months after onset of AMI, symptom-limited cardiopulmonary exercise tests were performed and the number of CD34⁺/133⁺ cells in the peripheral blood were measured by fluorescence-activated cell sorter analysis. At 3 months after AMI, the number of CD34⁺/133⁺ cells and oxygen consumption at anaerobic threshold were higher in the high exercise group (ie, exercise duration >4 h/week) than the low exercise group (ie, exercise duration <2 h/week). At 3 months after AMI, the number of CD34⁺/133⁺ cells significantly correlated with oxygen consumption at the anaerobic threshold (p=0.002). Conclusion Moderate daily exercise of >4 h/week increases exercise capacity and the number of circulating CD34⁺/133⁺ cells at 3 months after AMI. (Circ J 2008; 72: 897 - 901)

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Background This study compared the effect of 5 recumbent positions on cardiac autonomic nervous modulation in patients with coronary artery disease (CAD). Methods and Results Spectral heart rate variability analysis was performed on 33 CAD patients and 17 patients with patent coronary arteries in random order in 5 positions; namely, supine, right lateral decubitus, left lateral decubitus, left prone and right prone positions. In the right lateral decubitus position, the vagal modulation was the highest and the sympathetic modulation was the lowest among the 5 recumbent positions in the control group. In the CAD patients, the vagal modulation in the supine position was significantly lower than that in the other 4 positions. The lower the normalized high-frequency power (nHFP) in the supine position, the larger the percent age increase in nHFP when the position was changed from supine to another recumbent position in both CAD patients and controls. There was no significant change in the respiratory rate when the position was changed from supine to any of the other 4 positions. Conclusions Right lateral decubitus position leads to the highest vagal modulation in the controls, whereas the supine position leads to the lowest vagal modulation in the CAD patients. In addition to the right lateral decubitus position, both the right and left prone positions can be used as a vagal enhancer in patients with CAD as compared with supine, especially for those patients who have severely reduced cardiac vagal modulation while supine. (Circ J 2008; 72: 902 - 908)

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Background A community-based study was conducted to estimate the prevalence of atrial fibrillation (AF) in Japanese adults aged ≥40 years in Kurashiki-city and to examine associated risk factors. Methods and Results Adult residents (≥40-year-old) were examined in the Kurashiki-city Annual Medical Survey (KAMS) provided by the Kurashiki-city Public Health Center from May to December 2006. KAMS consisted of medical interviews, physical examination, blood testing and electrocardiography to assess the presence of AF. All participants were divided into AF and non-AF groups, their clinical characteristics compared, and the risk factors associated with AF investigated. Of 246,246 adult residents, 41,436 (age: 72.1±11.3 years; 13,963 men) underwent the KAMS. Estimated overall prevalence of AF was 1.6%. Multivariate analysis demonstrated that AF was independently associated with cardiac disease (odds ratio (OR), 9.00; 95% confidence interval (CI), 7.65-10.6; p<0.001), chronic kidney disease (OR, 1.76; 95%CI, 1.49-2.07; p<0.001), male sex (OR, 1.59; 95%CI, 1.34-1.85; p<0.001), and diabetes mellitus (OR, 1.46; 95%CI, 1.20-1.78; p<0.001). Hypercholesterolemia was highly associated with the absence of AF (OR, 0.54; 95%CI, 0.45-0.64, p<0.001). Conclusions Prevalence of AF in Japan is approximately 1.6%, lower than that in Western populations. Male sex, and cardiac and chronic kidney diseases are associated with the presence of AF. (Circ J 2008; 72: 909 - 913)

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Background Prognosis of Japanese patients with atrial fibrillation (AF) should be determined in a prospective cohort study. Methods and Results A prospective cohort of The Shinken Database 2004 comprised details on all the new patients who visited The Cardiovascular Institute Hospital in 2004 (n=2,412), which included 286 AF patients (11.8%, 205 males, 64.1±12.3 years, 165 paroxysmal). In this Japanese cohort of AF patients, the prevalence of congestive heart failure (CHF) was low compared with that in Westerners. Total mortality and cardiovascular morbidity of these patients were also quite low, 1.7% and 11.2% at 1 year, respectively. However, patients with CHF exhibited higher mortality (7.3%), and hospitalization for CHF increased the rate to 22.6%. There was no significant difference in mortality between paroxysmal and persistent AF. Multiple Cox-hazard regression analysis identified hospitalization at initial visit and lack of anticoagulation as independent predictors for mortality, and existence of CHF as the only independent predictor for cardiovascular morbidity. Conclusions The present study identified the mortality (1.7%) and morbidity (11.2%) of Japanese AF patients during 1 year after initial visit. Hospitalization for CHF and lack of anticoagulation were independent predictors for mortality, suggesting important roles of co-morbidities of Japanese AF patients. (Circ J 2008; 72: 914 - 920)

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Background The aim of the presnt study was: (1) to determine the predictive value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) on the success of an elective direct-current cardioversion; and (2) to assess the ability to monitor rhythm stability after electrical cardioversion in patients with lone atrial fibrillation (AF). Methods and Results Fifty-three patients with lone AF were provided with an Holter-ECG for a follow-up period of 4 weeks after elective cardioversion. NT-proBNP serum levels were measured before and 4 weeks after cardioversion. All patients presented with increased NT-proBNP serum levels (median 874 pg/ml, interquartile range 703-1,355) before cardioversion. Thirty patients were in sinus rhythm (SR) during follow-up. These patients showed a significant NT-proBNP-decrease (759 pg/ml, 618-1,139 to 318 pg/ml, 200-523, p<0.05). Nineteen patients experienced a relapse of AF. NT-proBNP was significantly higher prior to cardioversion in comparison to patients without relapse (p<0.05) and remained unchanged during follow-up (1,124 pg/ml, 925-1,542 vs 1,256 pg/ml, 945-1,509, p=NS). Four patients had short periods of silent AF detected by Holter ECG. These patients had a smaller decrease in NT-proBNP than patients with stable SR. The area under the curve of the receiver-operating characteristic curve was 0.8 for NT-proBNP to predict a successful cardioversion. Using an optimized cut-off level of 900 pg/ml, successful cardioversion can be predicted with high accuracy. Conclusions The probability of a successful cardioversion correlates inversely with NT-proBNP values. The short-term success of a cardioversion might be predicted by prior determination of NT-proBNP. (Circ J 2008; 72: 921 - 925)

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Background Patients on long-term hemodialysis become deficient in carnitine and are frequently treated with carnitine supplementation to offset their renal anemia, lipid abnormality and cardiac dysfunction. The therapeutic value of carnitine supplementation on left ventricular hypertrophy (LVH) in patients with normal cardiac systolic function remains uncertain. Methods and Results The cardiac morphology and function of 10 patients given 10 mg/kg of L-carnitine orally, immediately after hemodialysis sessions 3 times per week for a 12-month period were compared with 10 untreated control patients. Using echocardiography, left ventricular fractional shortening (LVFS) and left ventricular mass index (LVMI) were measured before and after the study period. As a result, amounts of serum-free carnitine increased from 28.4±4.7 to 58.5±12.1 μmol/L. The LVMI decreased significantly from 151.8±21.2 to 134.0±16.0 g/m² in treated patients (p<0.01), yet the LVMI in untreated control patients did not change significantly (ie, from 153.3±28.2 to 167.1±43.1 g/m²). However, LVFS values remained unchanged in both groups. Although L-carnitine promoted a 31% reduction in erythropoietin requirements, hematocrit and blood pressure did not change during the study period. Conclusions Supplementation with L-carnitine induced regression of LVH in patients on hemodialysis, even for those with normal systolic function. (Circ J 2008; 72: 926 - 931)

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Background Small dense low-density lipoprotein (sd-LDL) is an atherogenic lipoprotein closely associated with an increased risk of cardiovascular diseases. However, a precise analysis of the actual amount of sd-LDL-cholesterol (sd-LDL-C) in patients with metabolic syndrome (MS) has not been performed. Methods and Results Among 214 patients enrolled in the present study, 101 patients (47%) met the Japanese MS criteria. The serum levels of sd-LDL-C determined with a dual detection HPLC system were higher in MS than non-MS patients, while total cholesterol and low-density lipoprotein-cholesterol (LDL-C) were similar between MS and non-MS patients. Compared with the sd-LDL-C and LDL-C level, the ratio sd-LDL-C/LDL-C was more closely correlated with various parameters associated with MS. A multivariate regression analysis revealed that the ratio sd-LDL-C/LDL-C is the strongest independent determinant of hypoadiponectinemia. Furthermore, weight reduction therapy through diet and exercise rapidly decreased LDL-C but slowly decreased sd-LDL-C. At 12 months after the therapy, weight reduction led to a significant decrease in the ratio sd-LDL-C/LDL-C in tandem with increasing adiponectin levels. Conclusions These findings demonstrate that the ratio sd-LDL-C/LDL-C is tightly connected with hypoadiponectinemia and provides a useful clinical indicator for MS. The results also suggest that the elevation of this ratio can be modulated by long-term lifestyle changes. (Circ J 2008; 72: 932 - 939)

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Background Previous study has demonstrated that metabolic syndrome (MetS) can predict cardiovascular mortality in men, but the prediction was weak for women. In the present study predictors for multiple complex coronary lesions were investigated to clarify the impact of MetS in Japanese women with acute coronary syndrome (ACS). Methods and Results Subjects were Japanese women with ACS (n=81) who underwent emergency coronary angiography and B-mode carotid ultrasonography. They were divided into 2 groups based on the number of complex plaques. Although the MetS prevalence identified using the Japanese criteria was similar between the 2 groups, using the modified ATP III criteria it was more in patients with multiple coronary lesions than in those with a single coronary lesion (p<0.02). The prevalence of diabetes mellitus (DM) in the multiple group was higher than that in the single group (p<0.008). Significant independent predictors for multiple complex coronary lesions were DM (odds ratio (OR) 4.78, p<0.03) and carotid artery remodeling (OR 8.81, p<0.02). Among the components of MetS, a low level of high-density lipoprotein-cholesterol (<50 mg/dl) was a significant independent predictor (p<0.007). Conclusions DM and carotid artery remodeling are useful markers for coronary vulnerability in Japanese women. Gender-specific pathophysiological differences may exist for components of MetS. (Circ J 2008; 72: 940 - 945)

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Background Exercise training reduces walking disability in peripheral arterial disease (PAD). This non-randomized study evaluates the effects on walking ability and hemodynamic parameters of a novel approach to home-based rehabilitation, the test in -train out program (Ti-To), compared with the traditional home-based free walking exercise (Tr-E). Methods and Results A total of 143 patients with claudication (117 men, average age 68±10 years), were included in a Ti-To (n=83) or Tr-E program (n=60). Evaluations, which were carried out upon entry and at 1, 2, 3, 4 and 6 months, included: self-reported claudication, walking ability (ie, absolute claudication distance, pain threshold speed), resting/exercise heart rates (HR), systolic/diastolic brachial pressure (SBP/DBP), ankle pressure (AP), ankle-brachial index (ABI). Ti-To involved 2 daily 10-min home walking sessions at maximal asymptomatic speed and the patient attending monthly check-ups at hospital. Tr-E involved 20-30 min of daily walking at self-selected speeds up to pain tolerance. A total of 126 patients (Ti-To, n=74; Tr-E, n=52) completed the program. Ti-To induced better relief from claudication (p=0.001). Functional parameters improved significantly for both groups (p<0.0001) with significant intergroup difference for Ti-To (p<0.0001). SBP and exercise HR decreased significantly in both groups, with Ti-To improving resting HR (p=0.0002), DBP (p=0.003), lowest AP worse limb (p=0.004) and ABI worse limb (p=0.0002). Conclusions In patients with PAD, a Ti-To program had more positive effects on perceived claudication, and functional and hemodynamic parameters than did a Tr-E program. (Circ J 2008; 72: 946 -952)

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Background Small Q waves in the left lateral leads are termed septal q waves, and their response to exercise has been reported to be a marker of septal ischemia in coronary artery disease. Patients with hypertrophic cardiomyopathy (HCM) sometimes develop septal ischemia in the absence of coronary stenosis, but little data are available concerning the association of the septal q wave response with septal ischemia. Methods and Results Exercise electrocardiography and Tc-99m-tetrofosmin myocardial scintigraphy were recorded to detect myocardial ischemia in 29 HCM patients with asymmetric septal hypertrophy. The septal q wave amplitude was summed up in V₅ and V₆ during exercise testing, and the results were correlated with septal ischemia defined as a regional septal ischemia or a part of diffuse subendocardial ischemia. A decrease in the sum of the septal q wave amplitude during exercise testing yielded a sensitivity of 100% and specificity 33% for regional septal ischemia, and a sensitivity of 100% and specificity of 43% for diffuse subendocardial ischemia, although an absent septal q wave at rest provided a low sensitivity for the detection of regional septal ischemia (43%) and diffuse subendocardial ischemia (33%). Conclusions The septal q wave response to exercise is a useful marker of septal ischemia in HCM with asymmetric septal hypertrophy. (Circ J 2008; 72: 953 - 957)

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Background The validity of pulmonary thromboendarterectomy for treatment of relatively peripheral type of chronic thromboembolic pulmonary hypertension (CTEPH) remains uncertain. The survival and quality of life (QOL) of patients with relatively peripheral type of CTEPH was investigated at follow up. Methods and Results Between April 1999 and March 2006, 83 consecutive patients with CTEPH were evaluated for surgical indication and underwent computed tomography angiography. The extent of central disease was scored (ie, CD score), and a CD score of ≤1 was judged as relatively peripheral disease. Forty-three patients were excluded from surgery, and 40 patients, including 14 cases of relatively peripheral disease, underwent surgery. Long-term survival and QOL scores at follow up (1-3 years) were compared between the surgically and medically treated groups of relatively peripheral disease. Survival curves between the 2 treatment groups were not significantly different (p=0.78) because of high operative mortality (21.4%). However, improvement in physical functioning, role function (physically related), general health perception (as assessed by the Medical Outcome Study Short Form 36), and baseline dyspnea index were significantly higher in the group treated surgically compared with the medically treated group. Conclusions Pulmonary thromboendarterectomy offers better QOL even in those patients with relatively peripheral type of CTEPH, although operative mortality must be reduced. (Circ J 2008; 72: 958 - 965)

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Background Mortality from ischemic heart disease (IHD) has been showing a marked decline in Japan. The objective of this study was to clarify the effects of age, time period, and cohort on mortality from IHD in Japan from 1955 to 2000. Methods and Results IHD death data from vital statistics and national population surveys were tabulated for 11 5-year age groups (from 30-34 to 80-84) and 10 quinquennial demographic profiles (from 1955 to 2000), to yield 20 5-year birth cohorts (mid-years from 1873 to 1968). The stratified Age-Period-Cohort model with 7 age classes shows: (1) mainly linear age trends for men with IHD, but effects below the linear age trends for women in middle-aged groups (40-74 years); (2) a decline in the effect of time period on IHD for both men and women from 1970 to 1990, and a sharp increase between 1990 and 1995 along with the change of the International Classification of Diseases Code; and (3) 2 patterns for both sexes for non-linear birth cohort effects, an increase (1873-1928) and a decrease (1928-1968) for men, and an increase (1873-1923) and a decrease (1923-1968) for women, with a stronger effect for women than for men born between 1893 and 1938, but the reverse for men and women born between 1938 and 1968. Conclusion Declining effects of birth cohort on mortality rates of IHD for young and middle-aged people suggest that mortality rates are likely to continue to decrease in Japan. (Circ J 2008; 72: 966 - 972)

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Background Current definitions of overweight/obesity and central adiposity guidelines are based on Western populations, and may not be appropriate for the Chinese population. More data among Chinese are needed to address this issue. We aimed to identify cut-offs for body mass index (BMI) and waist circumference that confer increased risk of cardiovascular disease in a Chinese population in Shanghai. Methods and Results A representative, cross-sectional sample of 13,817 adults aged >18 years was studied in Shanghai. In men and women, blood pressure (systolic and diastolic), total cholesterol, low-density lipoprotein-cholesterol, triacylglycerol, and glucose values were incrementally higher and mean high-density lipoprotein-cholesterol values were incrementally lower with increased BMI and waist circumference. Both the point at which sensitivity equaled specificity and the shortest distance in the receiver operating characteristic curves for hypertension, dyslipidemia, diabetes, or ≥2 of these risk factors generally suggested a BMI cut-off value of 24 kg/m² for both men and women, and a waist circumference cut-off value of 85 cm for men and 80 cm for women. Conclusions A BMI cut-off of 24 kg/m² for both men and women, and a waist circumference cut-off of 85 cm for men and 80 cm for women might be appropriate for use in identifying adults at high risk of developing cardiovascular disease and serve as public health action thresholds in Shanghai residents. (Circ J 2008; 72: 973 - 978)

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Background The mechanism of alcohol-induced syncope is unknown. Methods and Results Head-up tilt tests (HUT: upright at 80° for 30 min) were performed before and after alcohol consumption in 25 patients with unexplained syncope after drinking alcohol. Plasma levels of epinephrine (P-E) and norepinephrine (P-NE) were measured in a supine position and during HUT (at 15 min). Before drinking alcohol, HUT did not provoke neurocardiogenic syncope (NCS) in any of the 25 patients. After drinking alcohol, HUT provoked NCS in 11 patients (alcohol-positive or AP group) but not in 14 patients (alcohol-negative or AN group). Prior to alcohol consumption, P-E and P-NE increased during HUT in both groups, and did not differ significantly between the 2 groups. After alcohol consumption, P-E and P-NE increased during HUT in both group. During HUT, P-NE did not differ between the 2 groups, but P-E was significantly higher in the AP group than in the AN group during HUT (258.0±179.2 vs 70.9±35.1 pg/ml, p<0.05). Conclusion These results suggest that an imbalance in the increases of adrenomedullar sympathetic nerve activity (as expressed by the P-E level) and peripheral sympathetic nerve activity (as expressed by the P-NE level) both induced by alcohol, may play a crucial role in alcohol-induced NCS. (Circ J 2008; 72: 979 - 985)

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Background Acute aortic dissection (AAD) is a life-threatening cardiovascular disorder that is similar to acute coronary syndrome (ACS), which means differentiating AAD and ACS is sometimes difficult in an emergency. Methods and Results Specific information from 131 patients with AAD or ACS was analyzed between April 2001 and March 2002. The emergency room AAD (ERAAD) score was defined as the total number of specific indexes for AAD among 15 indexes that were obtainable in the emergency room (Study 1). The clinical applicability of the ERAAD score was also investigated in another 711 patients with AAD or ACS between April 2002 and March 2006 (Study 2). The ERAAD score was based on (1) presence of back pain, (2) mediastinal thoracic ratio >30%, (3) aortic regurgitation and (4) aortic diameter >30 mm on ultrasonography in Study 1. The ERAAD score was significantly higher in patients with AAD than with ACS (3.19±0.83 vs 1.17±0.99) in Study 2. The sensitivity and specificity for AAD were 93.1% and 77.6%, respectively, when the ERAAD score was ≥3. Conclusion The ERAAD score enables clinical diagnosis of AAD and correct treatment. (Circ J 2008; 72: 986 - 990)

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Background A previous history of myocardial infarction (MI), stroke, and the presence of atrial fibrillation (AF) are known risk factors for the onset of arterial thromboembolic events such as MI and ischemic stroke. To clarify the rate of incidence of such events for these high-risk patients in Japan, a nation-wide cohort study was conducted that was named the `Japan Thrombosis Registry of Atrial Fibrillation, Coronary and Cerebrovascular Events' (ie, J-TRACE) [UMIN Registered ID C000000189]. Methods and Results In the J-TRACE registry, a total of 8,093 Japanese patients with either a history of stroke and/or MI or patients with non-valvular AF were registered. This registry was developed by specialists in cardiology and neurology, physicians working at general hospitals, as well as general practice physicians, from whole regions of Japan, possibly reflecting the real-world medical practice. Recruited patients will be followed up for 2-3 years. Medical history, accompanying risk factors, demographic characteristics, and information regarding the use of medications were collected for these patients at baseline. Cardiovascular ischemic events and serious adverse experiences, including cerebral bleedings, which occur during the follow-up period will be recorded over a maximum of 3 years. Conclusion The J-TRACE offers an opportunity to provide fundamental information regarding the incidence of cardiovascular ischemic events by a stratum of the risk factor profile and current medical treatment for Japanese patients at high risk for thromboembolic diseases. (Circ J 2008; 72: 991 - 997)

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Background We examined whether nitroglycerin (NTG)-induced impairment of nitric oxide (NO) bioavailability could be modified by a peroxisome proliferator-activated receptor (PPAR) γagonist. Methods and Results Male New Zealand White rabbits were treated for 7 days with NTG patches, either alone or in combination with pioglitazone. Plasma NO concentration was measured with the catheter-type NO sensor located in the aorta. N^G-methyl-L-arginine and acetylcholine (ACh) were infused into the aortic arch to measure the basal and ACh-induced plasma NO concentrations. Vascular nitrotyrosine and tetrahydrobiopterin (BH₄) concentrations were measured by enzyme-linked immunosorbent assay and high-performance liquid chromatography with fluorescence detection, respectively. The negative effects of NTG, that is, the decrease in basal and ACh-induced NO production, were significantly suppressed by co-treatment with pioglitazone. NTG-induced increases in vascular nitrotyrosine and BH₄ concentrations were significantly decreased with co-treatment with pioglitazone. Conclusions NTG-induced impairment of basal and ACh-stimulated NO production might be prevented by the co-treatment with a PPAR γ agonist, pioglitazone through suppressions of nitrosative stress. (Circ J 2008; 72: 998 - 1002)

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Background Bepridil is known to have a multiple ion channel-blocking property in the heart, which has been applied for the treatment of atrial fibrillation and drug-refractory ventricular tachyarrhythmias. In this study, the electro-pharmacological effects of bepridil were compared with those of dl-sotalol, a representative class III antiarrhythmic drug, using the halothane-anesthetized canine model. Methods and Results Cardiovascular and electrophysiological variables were measured under the halothane anesthesia. Intravenous administration of bepridil (0.3 mg/kg, n=4) delayed the intraventricular conduction and prolonged the ventricular effective refractory period, whereas dl-sotalol (0.3 mg/kg, iv, n=4) inhibited atrioventricular conduction and prolonged the atrial and ventricular effective refractory period. The additional administration of 10 times the higher dose of bepridil or dl-sotalol (ie, 3 mg/kg, iv, n=4 for each group) decreased blood pressure, suppressed ventricular contraction and sinus automaticity, and prolonged the atrial and ventricular effective refractory period and monophasic action potential duration, in addition to the effects of the low dose. Conclusions The electropharmacological effects of bepridil and dl-sotalol were similar, although their potency for each cardiovascular variable varied significantly. These findings can be useful when selecting these drugs according to the pathophysiological condition of a patient. (Circ J 2008; 72: 1003 - 1011)

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Background Sepsis can be exacerbated by an inappropriate immune response and the severe impact of this disease on the cardiovascular system is well documented. High mobility group box 1 (HMGB1) protein is an important mediator in the pathogenesis of sepsis and its role in cardiovascular system dysfunction was investigated in an lipopolysaccharide (LPS)-induced rat model of sepsis. Methods and Results Twelve hours after intravenous bolus injections of LPS (5 mg/kg), rats were killed and heart samples were harvested. Immunoblot analysis was performed to assess expression levels of HMGB1 in cardiac myocytes. Left ventricular developed pressure (LVDP) served as a measure of systolic function. LPS administration was associated with an increase in the expression of HMGB1 in cardiac myocytes and a decrease in cardiac function. Hearts from the LPS-treated rats were also perfused with recombinant HMGB1 and cardiac function measured. The dose-dependent effects observed with elevated HMGB1 included decreased LVDP, decreased left ventricular (LV) + dP/dt_max, decreased absolute value of LV- dP/dt_min, and increased LV end-diastolic pressure. Conclusions HMGB1 stimulation produces a negative inotropic effect during septic shock, suggesting an important role for this molecule in cardiovascular system dysfunction during sepsis. (Circ J 2008; 72: 1012 - 1017)

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Background A trafficking defect of mutant cardiac Na-channels (SCN5A) has been implicated in Brugada syndrome. Although R1232W polymorphism and T1620M mutation by themselves have little effect on Na-channel function, their combination has been reported to disrupt membrane trafficking, resulting in a non-functioning Na channel. Methods and Results Contrary to previous findings, patch-clamp recordings of heterologously expressed R1232W/T1620M showed robust Na currents and confocal microscopy exhibited predominant expression in the plasma membrane, similar to the wild-type channel. Conclusions It is unlikely that an intragenic interaction between R1232W and T1620M of SCN5A causes a trafficking defect leading to a non-functioning Na channel. (Circ J 2008; 72: 1018 - 1019)

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Background High-speed rotational coronary venous (CV) angiography (RCVA) permits dynamic, multi-angle visualization of the CV anatomy. Methods and Results RCVA uses a rapid isocentric rotation over a 108° arc, right anterior oblique (RAO) 54° to left anterior oblique (LAO) 54°, in 4 s. Three-dimensional models of the venous tree were reconstructed, and the rotational images were analyzed using a full range of gantry angles, providing the operator with considerably more information about the CV anatomy than standard coronary sinus angiography images (SCVA). Conclusions The SCVA view, which optimally displayed the appropriate coronary sinus branch for left ventricular lead implantation, was often different from the conventional RAO and LAO views. (Circ J 2008; 72: 1020 - 1021)

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Bartonella (Rochalimaea) species are increasingly recognized as a cause of endocarditis, but the total number of cases remains low. Especially, Bartonella quintana endocarditis is very rare and there have been no reports in Japan. A 66-year-old man was hospitalized because of dyspnea and fever. An echocardiogram showed severe mitral valve regurgitation, mild aortic valve regurgitation, and echogenic masses on the mitral and aortic valve. Six sets of blood cultures were negative. Replacement of the mitral- and aortic-valve with a mechanical valve was performed. However, due to symptomatic para-valvular leakage a re-mitral valve replacement was later performed. Unfortunately, the patient died 1 month after the operation owing to multiple organ failure. Four weeks after the second operation, blood culture yielded a Gram-negative bacillus. DNA was extracted from the colony and subjected to polymerase chain reaction amplification. Nucleotide sequence analysis (1,500 nucleotide positions) and a BLAST search of the EMBL/GENBANK database revealed 99.9% homology with the Bartonella quintana 16S rRNA gene. This is the first report of Bartonella quintana endocarditis in Japan, and should be considered with the view of culture negative endocarditis. (Circ J 2008; 72: 1022 - 1024)

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The case of a 41-year-old man with Brugada syndrome (BS) who suffered electrical storms (ES) of ventricular fibrillation (VF) is presented. Although intravenous infusion of isoproterenol (ISP) suppressed the VF occurrence, he consistently experienced recurrence of VF following discontinuation of ISP infusion. Quinidine and cilostazol were ineffective. An analysis of VF episodes on electrocardiogram monitoring revealed that the QRS morphology of the first beat of all VF episodes was identical to that of premature ventricular complexes (PVCs) with a left bundle branch-block morphology and inferior axis, which occurred repetitively before the episodes of VF and were recorded throughout the day. In addition, stored electrograms from the implantable cardioverter defibrillator showed that the first beat of all VF episodes had the same morphology. On electrophysiological study, the VF-triggering PVC was found to originate from the posterior portion of the right ventricular outflow tract area and their elimination, which was achieved with radiofrequency catheter ablation (RFCA), resulted in the suppression of ES. Although several other PVCs were still observed, the patient has been free of VF during the 29-month follow-up period. This case indicates that RFCA of VF-triggering PVCs may be useful in the treatment of drug-resistant ES in patients with BS. (Circ J 2008; 72: 1025 - 1029)

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Patients with chronic heart failure (HF) not infrequently present conduction disturbances, which are most commonly exhibited as a left bundle branch block (LBBB). LBBB is associated with intraventricular conduction delay, paradoxical septal motion, and hemodynamic deterioration, indicating an impairment of left ventricular (LV) function. However, there is controversy as to whether dilated cardiomyopathy leading to HF could develop just as a result of conduction disturbances without apparent pre-existing heart disease. We report here 2 cases of patients with non-ischemic dilated cardiomyopathy and LBBB who had complete reversal of their LV dysfunction and enlargement after cardiac resynchronization therapy, which corrects the LV activation sequence. These cases might support the idea that conduction disturbances themselves can be a principal etiology in the development of dilated cardiomyopathy. (Circ J 2008; 72: 1030 - 1033)

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Simultaneous double vessel acute myocardial infarction (AMI) is extremely rare and usually has poor clinical outcomes. Management of this complicated condition is challenging and time-limited. The case of a 46-year-old Taiwanese man with simultaneous anterior and inferior wall AMI is reported. Rapid deterioration of clinical condition with ventricular fibrillations (VF), cardiogenic shock and asystole developed before catheterization. Coronary angiogram revealed simultaneous total occlusion of left anterior descending (LAD) and right coronary arteries (RCA). Frequent VF attack was still noted after diagnostic catheterization. After cardiopulmonary resuscitation, immediate percutaneous coronary intervention of the LAD and RCA, and intra-aortic balloon counterpulsation was inserted. Due to intractable heart failure and cardiogenic shock, extracorporeal membrane oxygenation was performed. Rabdomyolysis with acute renal failure was also noted with hemodialysis treatment. Thirty-one days after hospitalization, he was discharged with a New York Heart Association functional class III heart failure, without hemodialysis. (Circ J 2008; 72: 1034 - 1036)

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