Background The effects of glucose abnormalities on outcomes after percutaneous coronary intervention (PCI) remain unclear. We examined the association between glucose abnormalities and in-hospital outcome in patients undergoing PCI for acute myocardial infarction (AMI). Methods and Results A total of 849 patients with AMI who were admitted within 12 h after symptom onset and underwent emergency PCI were classified according to the presence or absence of admission hyperglycemia, defined as a blood glucose level on admission of >11 mmol/L and whether they had a history of diabetes mellitus: group 1 (n=504), non-diabetic patients without admission hyperglycemia; group 2 (n=111), diabetic patients without admission hyperglycemia; group 3 (n=87), non-diabetic patients with admission hyperglycemia; and group 4 (n=147), diabetic patients with admission hyperglycemia. Among groups 1, 2, 3 and 4, in-hospital mortality was 2.6, 2.7, 11.5 and 8.8%, respectively (p<0.01). Multivariate analysis showed that compared with group 1 patients, the odds ratio (95%confidence interval) for in-hospital mortality among those in groups 2, 3, and 4 were 0.80 (0.24-2.60, p=0.708), 2.29 (1.10-5.49, p=0.039), and 2.14 (1.14-4.69, p=0.048), respectively. Conclusions In-patients undergoing PCI for AMI, admission hyperglycemia, irrespective of the presence or absence of diabetes, is associated with increased in-hospital mortality, whereas diabetes without admission hyperglycemia is not. (Circ J 2005; 69: 375 - 379)

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Background The present retrospective study was performed to assess the long-term (>7 years) fate of stabilized balloon-dilated sites. Methods and Results Between February and April 1986, 171 patients underwent successful percutaneous balloon angioplasty. Early restenosis (<1 year) occurred in 53%, but repeat balloon angioplasty stabilized the balloon-dilated site. The early period was defined as 6 months, late years as 3-5 years and long-term years as 7-12 years. Angiographic evaluation at both early year or late year periods (mean =4.7 years) and long-term (mean =10.4 years) periods following stabilization was available in 71 patients (94 lesions) with mean age of 61.7±8.5 years. Of the 71 patients 69.6% were male. Restenosis occurring after 1 year was defined as late restenosis. The mean diameter stenosis changed from 6 months (50.3±12.4%) to late-period (44.2 ±13.2%; p<0.05) and long-term period (50.3±16.1%; p<0.001); but the reference vessel diameter did not change significantly. Late restenosis occurred in 28% (3-5 years) and 33% (7-12 years) of 94 lesions, and 13.8% of lesion required repeat target lesion revascularization. During this period, 5.3% of patients (5 lesions) underwent revascularization for new proximal or distal lesions. Conclusions Decrease of luminal diameter during the early 6 months, was followed by regression after stabilization of the balloon-dilated site up to 5 years, but luminal re-narrowing occurs again over 7 years after balloon angioplasty. (Circ J 2005; 69: 380 - 385)

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Background The gender differences in the association between C-reactive protein (CRP) and features of the metabolic syndrome (MS) need to be elucidated among Japanese. Methods and Results The study population included 715 men and 988 women aged 40-69 years who were not taking anti-hypertensive, lipid-lowering, hypoglycemic, anti-thrombotic, or non-steroidal anti-inflammation medications, and did not have a past history of cardiovascular disease or CRP concentration >10 mg/L. Except for high-density lipoprotein cholesterol, the unadjusted correlation between CRP and each MS component, including body mass index (BMI), systolic and diastolic blood pressures, triglycerides, fasting glucose, fasting insulin, and uric acid, was greater in women than in men. With adjustment for age, smoking status, and drinking status, the differences in CRP concentrations between those with the MS components of BMI, triglycerides, and uric acid and those without were greater in women than in men. Results of stratified analyses by the number of components of the MS of 0, 1, 2, 3, and ≥4 revealed that an increase in CRP concentrations was greater in women than men with an increased number of components of the MS (gender interaction, p=0.005). This tendency was observed in non-smokers, but not in current smokers (gender interaction, p=0.013 and =0.513, respectively). Conclusions CRP concentrations are closely related to the MS-like state in both sexes, but an increase in CRP concentration associated with risk factor-clustering is more pronounced in women, particularly non-smokers. (Circ J 2005; 69: 386 - 391)

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Background Little information is available regarding the incidence of aortic dissection or rupture in patients with a dilated ascending aorta after aortic valve replacement (AVR). The present clinical study aimed to demonstrate the incidence of aortic complications after AVR in patients with a dilated ascending aorta and to clarify those risk factors associated with the progression of a dilated ascending aorta or late aortic events. Methods and Results A total of 35 patients with a dilated ascending aorta at the time of AVR were enrolled. A dilated ascending aorta was defined as 40 mm or greater in diameter by preoperative computed tomography or operative findings. The baseline ascending aorta diameter ranged from 40 to 55 mm with a mean of 44.8±4.4 mm. There was a high frequency of bicuspid valve disease in patients with a dilated ascending aorta (57%). The mean follow-up interval was 8.1±3.5 years (range: 2.3-13). Aortic events occurred in 5 patients (aortic dissection in 1, rupture in 2, reoperation in 2) during the follow-up. One aortic dissection developed at a baseline aortic size of 42 mm, whereas 2 aortic ruptures occurred at baseline aortic sizes of 47 mm and 50 mm. There was no statistically significant univariate association between any of the patient clinical characteristics and late aortic events or ascending aortic progression. Conclusion Although the clinical course of patients with a dilated ascending aorta is unpredictable, aortic events may occur even in patients with a baseline aortic diameter of <50 mm. Therefore, preventive aortic surgery at the time of AVR should be considered to prevent aortic dissection or rupture in patients with an even slightly dilated ascending aorta with a diameter of 40 to 50 mm, unless the patient has a high operative risk or older age. (Circ J 2005; 69: 392 - 396)

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Background A rapid laboratory test for diagnosis of acute aortic dissection (AAD) has not been available. We performed this prospective study to determine the utility of a rapid bedside D-dimer (DD) assay for detection of AAD. Methods and Results Patients with suspected AAD were recruited and their DD levels were measured by rapid bedside assay. They were divided into 2 groups according to enhanced computed tomography findings: an AAD group (n=30) and a non-AAD group (n=48). The median DD level was higher in the AAD group (1.80 μg/ml) than in the non-AAD group (0.42 μg/ml) (p=0.000). The rapid bedside DD assay showed 100% sensitivity, 54% specificity, 58% positive predictive value and 100% negative predictive value for detection of AAD with a normal DD level of up to 0.5 μg/ml. The combination of DD level >0.5 μg/ml and systolic blood pressure ≥180 mmHg showed 86% positive predictive value for detection of AAD. Conclusions We conclude that the rapid bedside DD assay is a highly sensitive method for early exclusion of AAD in patients with chest and/or back pain suggestive of AAD. Acute aortic dissection is highly probable if a rapid DD assay shows the elevated DD level with systolic blood pressure ≥180 mmHg on admission. (Circ J 2005; 69: 397 - 403)

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Background The incidence and mortality from ischemic heart disease (IHD) in Japan seem to be among the lowest of all the industrialized countries, but there are few reliable registers of acute myocardial infarction (AMI). Methods and Results To assess the incidence of AMI in Takashima County, Shiga, Japan, from 1988 to 1998 and compare the data with similar registers in the world, cases of AMI or sudden death presumed from myocardial ischemia were registered. The criteria of AMI were based on the WHO MONICA Projects. The medical records of all the hospitals inside as well as outside the county, the original death records in the health center, and the ambulance records in the county were investigated and 291 cases were registered (190 males, 101 females; average age (mean ± SD), 69.5±12.2). The 28-day and 24-h case fatality was 38.1% and 33.0%, respectively. Age-adjusted annual incidence of AMI per 100,000 population aged between 25 and 74 years were 58.2 for men and 18.0 for women. The incidence of AMI showed a constant trend from 1988 to 1998. Conclusion The results confirmed that Japan has the lowest incidence of AMI among the industrialized countries. (Circ J 2005; 69: 404 - 408)

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Background Men with a prolonged corrected QT (QTc) interval have an increased risk of cardiovascular mortality and sudden death, even in healthy individuals. In addition, prolonged QTc is a predictor of mortality in diabetics. However, the relationship between insulin resistance and QTc is not clarified in non-diabetic healthy people. The present study was performed to observe the association between QTc and insulin resistance in Korean non-diabetic subjects. Methods and Results In the current study there was a total of 874 subjects (520 men, 354 women, mean age: 45.9±11.0 years) who underwent a medical check-up at the health promotion center at Kangbuk Samsung Hospital from January 2002 to May 2002. Age, sex, height, body weight, blood pressure, blood cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), fasting insulin, and fasting glucose levels were measured. The QT intervals were corrected using Bazett's formula (QTc = QT/√RR). Homeostasis model assessments (HOMA) were performed to assess the correlation between insulin resistance indices and the QTc interval. The mean QTc interval was significantly longer in females (417±24 ms) than in males (402±23 ms) (p<0.001). After adjusting the variables related to the QTc interval, the differences in QTc between men and women were statistically significant (p<0.001). A significant positive correlation was found between QTc and age, glucose, and blood pressure in male subjects. Female subjects showed positive correlation between QTc and age, glucose, blood pressure, total cholesterol, low-density lipoprotein cholesterol, triglyceride, fasting insulin, and the HOMA index, and a negative correlation between QTc and HDL-C. Multiple regression analysis showed that in men, age (β=0.480, p<0.001) and diastolic blood pressure (β=0.280, p<0.001) were predictors of QTc. In women, age (β=0.321, p=0.008), diastolic blood pressure (β=0.324, p=0.006) and HOMA index (β=3.508, p=0.033) were predictors of QTc. Conclusions The present study of Korean healthy subjects shows that QTc was more prolonged in females than in males. In normoglycemic female subjects, insulin resistance was an independent determinant of the prolongation of QTc. (Circ J 2005; 69: 409 - 413)

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Background Patterns of arterial remodeling during the course of plaque development have been shown to play an important role in both the progression of de novo atherosclerosis and in the restenotic process following coronary intervention. The aim of the present prospective study was to evaluate the effect of pre-interventional arterial remodeling on in-stent neointimal hyperplasia (NIH) and in-stent restenosis (ISR) after stenting. Methods and Results Pre-interventional arterial remodeling was assessed in 85 native coronary lesions by using intravascular ultrasound (IVUS). The remodeling index (RI) was 1.09±0.20 in the positive remodeling (PR)/intermediate remodeling (IR) group and 0.84±0.12 in the negative remodeling (NR) group. The plaque plus media cross sectional area (P&M CSA) at pre-intervention and NIH CSA at follow-up in the minimal lumen CSA were significantly larger in the PR/IR group (9.2±2.9 mm² vs 6.2±1.8 mm², 3.3±1.2 mm² vs 1.5±0.9 mm²; p=0.001, p=0.001, respectively). On 3-dimensional analysis of IVUS images at follow-up, the lumen volume was significantly smaller in the PR/IR group than that in the NR group (62±15 mm³ vs 75 ±20 mm³; p=0.001), and neointima hyperplasia volume was significantly larger in the PR/IR group than that in the NR group (46±15 mm³ vs 26±10 mm³; p=0.001). A significant positive correlation was found between pre-interventional RI and follow-up NIH CSA (r=0.25, p=0.022). The incidence of ISR and repeat intervention was significantly higher in the PR/IR group (30.8% vs 18.2%, 28.8% vs 15.2%; p=0.032, 0.035, respectively). Conclusion Measuring pre-interventional arterial remodeling patterns by IVUS may be helpful to stratify lesions at high-risk of ISR. (Circ J 2005; 69: 414 - 419)

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Background Many patients with acute myocardial infarction will still die after admission. Recent trends in hospital mortality were analyzed to identify aspects that need improvement. Methods and Results A total of 1,247 patients admitted to Kinki University School of Medicine within 24 h of the onset of infarction were analyzed between 1975 and 2001. The percentage of patients discharged with 100% occlusion decreased gradually from 31.3% during 1975-1982 to 2.1% during 1998-2001, while those with 50% stenosis or less gradually increased from 12.5% to 82.5% during the same period (trends: p<0.01). The cardiac death rate was 17.1% in 1975-1982, and 7.7% in 1998-2001, showing a significant decrease with time (p<0.01). This decrease was particularly marked among those admitted within 6 h of the onset of infarction. Death due to cardiac rupture decreased significantly with time (p<0.001). In contrast, the non-cardiac death rate, amounting to 2.2% on average, did not decline. Conclusions Cardiac deaths due to acute myocardial infarction have decreased markedly of late. However, patients must be admitted within 6 h of the onset of infarction to benefit from this improvement. More effort should be made to improve the general care of patients in order to reduce the incidence of non-cardiac death. (Circ J 2005; 69: 420 - 426)

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Background It remains unclear whether spontaneous anterograde flow preserves myocardial fatty acid metabolism in patients with acute myocardial infarction (AMI). Methods and Results The present study comprised 129 patients with a first anterior AMI in whom Thrombolysis in Myocardial Infarction (TIMI) 3 flow was obtained on the final angiogram: 28 patients with spontaneous anterograde flow and 101 patients with total occlusion on the initial angiogram. Thallium-201 (²⁰¹Tl) and iodine-123-β-methyl-p-iodophenyl penta-decanoic acid (¹²³I-BMIPP) dual-isotope myocardial single-photon emission computed tomography (SPECT) was performed at 6.5±4.2 days after onset. The SPECT image was divided into 17 segments, and each segment was graded with scores between 0 and 4 (0, normal uptake; 4, defective). The sum of each score was defined as the total defect score (TDS). TDS values for ²⁰¹Tl (9.0 ±7.4 vs 16.8±12.2, p<0.01) and ¹²³I-BMIPP (19.3±11.6 vs 24.1 ±10.4, p<0.05) were significantly lower in patients with spontaneous anterograde flow than in those with total occlusion. Conclusions These results suggest that spontaneous anterograde flow of the infarct artery preserves not only myocardial perfusion but also fatty acid metabolism in patients with AMI. ¹²³I-BMIPP SPECT image may underestimate the area at risk especially in patients with spontaneous anterograde flow. (Circ J 2005; 69: 427 - 431)

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Background Left ventricular end-diastolic pressure (LVEDP) is difficult to measure continuously; therefore, pulmonary capillary wedge pressure (PCWP) is frequently used instead for hemodynamic monitoring in patients with heart failure. However, a discrepancy between LVEDP and mean PCWP is sometimes observed. Methods and Results To assess the feasibility of evaluating this discrepancy using echo-Doppler indexes, 140 consecutive patients with heart disease were studied. Transthoracic Doppler echocardiography (TTDE) was performed immediately before bilateral-sided cardiac catheterization. We measured peak velocities of early (E: cm/s) and late (A: cm/s) diastolic transmitral flow, and duration of A wave (MAd: ms). We also measured the duration of atrial reversal of pulmonary venous flow (PAd: ms). The difference between PAd and MAd (Δd = PAd-MAd: ms) was calculated. The ratio of E to tissue Doppler-derived peak early diastolic velocity of mitral annulus (Ea: cm/s) was also calculated (E/Ea). There was a good positive correlation between LVEDP and Δd (r=0.77, p<0.001). There was a modest correlation between mean PCWP and E/Ea (r=0.56, p<0.001). When patients were classified by Δd ≥10 ms and E/Ea ≤14, elevated LVEDP (≥17 mmHg) and normal mean PCWP (≤12 mmHg) were predicted with 100% sensitivity and 85% specificity. Conclusions Evaluation of the discrepancy between LVEDP and mean PCWP in patients with heart failure was feasible by separately estimating LVEDP by Δd and mean PCWP by E/Ea using noninvasive TTDE. Early detection of patients with elevated LVEDP and normal mean PCWP may be useful for preventing acute exacerbation of chronic heart failure. (Circ J 2005; 69: 432 - 438)

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Background Regional left ventricular (LV) diastolic wall motion abnormalities detected by color kinesis (CK), an echocardiographic technique, may be a more sensitive measure to postischemic damage following coronary spasm than parameters of global diastolic function. Methods and Results Regional LV diastolic wall motion was evaluated by using CK in 18 patients with variant angina on the day following coronary spasm, which was induced by intracoronary acetylcholine. Fractional regional LV cavity area expansion in the short-axis view during the first 30% of the LV filling time, was used to identify postischemic asynchronous diastolic wall motion. Regional delayed relaxation was observed in any of the LV regions in all the patients, who were divided into 2 groups (Group S: 7 patients with single-vessel spasm with regional delayed relaxation in one area. Group M: 11 patients with multivessel spasm or spasm of the proximal left anterior descending branch with regional delayed relaxation in multiple areas). In Group S, no abnormality (0%) was noted in any of the indexes of global diastolic function including the isovolumic relaxation time, the ratio of peak rapid filling to peak atrial filling velocities and the deceleration time. In contrast, in 5 (45%) of the Group M patients, abnormalities were noted in all of those indexes. Conclusions Postischemic regional LV-delayed relaxation following coronary vasospasm was detected sensitively by analysis of CK images. The indexes of global LV diastolic function are insensitive to postischemic damage following single vessel spasm, although they are somewhat sensitive following multivessel spasm. (Circ J 2005; 69: 439 - 445)

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Background We sought to identify factors favoring long-term restoration of sinus rhythm (SR) in patients with atrial fibrillation (AF) who underwent a simple cryoablation of pulmonary vein orifices (PV-cryo) as part of their cardiac surgery. Methods and Results Of 101 patients with AF undergoing PV-cryo, the 71 in SR at discharge were grouped according to whether they maintained or lost SR (group SR, n=61, and group AF, n=10) after an average of 2.3 years. Atrial fibrillation present at discharge (n=30) persisted during follow up. Comparisons were made to identify preoperative predictive factors, including transthoracic and transesophageal echocardiographic parameters. Of patients discharged from the hospital with SR, 92% (46 of 50) of those with AF duration of 3 years or less were in group SR, as were 92% (23 of 25) of those with left atrial dimension of 50 mm or less, and 93% (37 of 40) of those with average peak left atrial appendage outflow velocities (LAA-V) of at least 30 cm/s. Of 25 patients in group SR who had no paroxysmal AF and did not require antiarrhythmic drugs, all had LAA-V over 20 cm/s. Patients in group AF all had LAA-V under 40 cm/s. Conclusions Left atrial appendage outflow velocities was the best predictor of whether SR was maintained long-term after PV-cryo. (Circ J 2005; 69: 446 - 451)

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Background Increased levels of inflammation markers, such as C-reactive protein (CRP) and tumor necrosis factor-α , have been found in insulin resistance syndrome. Those with elevated levels of high-sensitive CRP (hs-CRP) are at a higher risk for coronary heart disease. In the present study, we evaluated whether maximum oxygen uptake and insulin resistance are related to hs-CRP for the primary prevention of coronary heart disease. Methods and Results The subjects were 50 subjects who did not have diabetes mellitus. A multi-step treadmill exercise test was performed to obtain the maximum oxygen uptake when assessed by computerized breath-by-breath analysis. As an index of insulin resistance, the homeostasis model insulin resistance index (HOMA-R; fasting glucose × fasting insulin/405) was used. In addition, bodyweight, body mass index, subcutaneous fat thickness, total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride were measured. Multivariate analysis revealed that hs-CRP was significantly correlated with HDL-cholesterol, uric acid, γ-glutamyl transpeptidase and maximum oxygen uptake. The maximum oxygen uptake showed the smallest odds ratio was in terms of the relationship with hs-CRP. Conclusions The present study suggests that the development of exercising habits increases the maximum oxygen uptake. Furthermore, an elevated maximum oxygen uptake decreases HOMA-R and reduces the inflammatory marker CRP, suggesting that exercising habit plays an important role in the primary prevention of coronary heart disease. (Circ J 2005; 69: 452 - 457)

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Background Constrictive pericarditis is an uncommon disease that prevents the normal diastolic filling of the heart and pericardiectomy is the only satisfactory treatment. Methods and Results The clinical characteristics and treatment of patients who underwent pericardiectomy for constrictive pericarditis (n=23) were reviewed. Surgery was performed via left anterolateral thoracotomy plus transsternal extension in 3 patients, and median sternotomy in 20 patients. There were 2 deaths, resulting in an overall mortality rate of 8.7%. Of the 23 patients, 8 had Mycobacterium tuberculosis (Tb) infection, 2 had streptococcus infection, 1 had strongyloidiasis (Strongyloides stercoralis) and 1 developed the condition after a myocardial infarction; 2 patients underwent pericardial substitute insertion as post-heart surgery, and 3 patients had connective tissue disorders; 6 patients had idiopathic disease. Conclusion These results show that bacterial infection, especially Tb, is a major etiology of constrictive pericarditis in Taiwan and that median sternotomy is an excellent approach for exposing the heart for pericardiectomy. (Circ J 2005; 69: 458 - 460)

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Background Epoprostenol (prostaglandin I₂) has become recognized as a therapeutic breakthrough that can improve hemodynamics and survival in patients with primary pulmonary hypertension (PPH). However, a significant number of patients have PPH that is refractory to epoprostenol, and lung transplantation has been the only remaining treatment option. Methods and Results The study subjects included 20 consecutive patients with PPH (mean pulmonary arterial pressure: 65±15 mmHg) who had received epoprostenol for more than 12 months. The patients were divided into 2 groups; responders and non-responders. In the non-responders, New York Heart Association (NYHA) functional class did not improve and mean right atrial pressure (mRA) increased to 8 mmHg or more, and additional sildenafil, a phosphodiesterase-5 inhibitor, was started. Six patients were included in the non-responders, whose mRA was 9±5 mmHg before and significantly increased to 13±3 mmHg after epoprostenol administration (p<0.05). One patient died and the other 5 patients received oral sildenafil. The mRA of 12±4 mmHg (value before sildenafil) improved to 8±5 mmHg after sildenafil administration. Three patients were classified in the NYHA functional class 4 and improved to class 3, and 2 patients were in class 3 and remained in the same class after the addition of sildenafil. Conclusions In patients with severe PPH refractory to epoprostenol treatment, additional oral sildenafil can improve pulmonary hemodynamics and symptoms. The combination therapy of epoprostenol and sildenafil is a new medical treatment to attempt before progressing to lung transplantation for patients with PPH refractory to epoprostenol. (Circ J 2005; 69: 461 - 465)

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Background The aim of the present study was to describe the effectiveness and feasibility of high-resolution computed tomography (HRCT) in patients in supine and prone positions to detect amiodarone-induced pulmonary toxicity (APT). With regard to the possible differential diagnosis, our second goal was to emphasize the clinical value of HRCT with the patients in supine and prone positions compared with other paraclinical tests. Methods and Results Thoracic HRCT taken in both positions for 23 patients who were administrated amiodarone were prospectively evaluated in the current study. High-resolution computed tomography scans obtained with the patient in a prone position were helpful in differentiating dependent opacity from lung disease in 11 out of 23 patients. In another 4 patients, HRCT scans obtained with the patient in a prone position were useful in confirming the presence of subtle ground-glass opacities, considered as APT. Combination of HRCT in supine and prone positions provided a more reproducible method for evaluating the global extent of APT than other paraclinical tests. Conclusions High-resolution computed tomography used in prone positions as well as a supine position could be an effective technique for reducing false-positive results in detection of APT and preventing the clinically serious pulmonary adverse effects by amiodanone. (Circ J 2005; 69: 466 - 470)

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Background The aim of the present study was to investigate whether the chronotropic index (CRI) is independent of age, sex, stage of exercise testing, functional capacity and resting heart rate in children, as it is in adult populations. Methods and Results A total of 129 normal children and adolescents underwent maximal treadmill exercise testing according to the Bruce protocol. Submaximal chronotropic response was assessed by the CRI at the end of stages 1, 2, 3, and 4 of Bruce treadmill exercise testing. The CRI assessed at each exercise stage was independent of sex, maximal oxygen uptake and resting heart rate. The CRI was independent of age when measured at stages 3 and 4 in boys and at stage 4 in girls, but was weakly correlated with age when measured at stages 1 and 2 in boys and at stages 1, 2 and 3 in girls. There was a significant effect of exercise intensity on the CRI: multiple comparisons revealed that, in girls, CRI assessed at stage 1 was greater than that assessed at stage 4. Also, lower exercise stages resulted in rather large variations in the measurement. Conclusion The results essentially confirm the potential applicability of the CRI for children and adolescents, although care should be taken in evaluating measurements of the CRI in the early stages of exercise testing to avoid misinterpretation of the results. (Circ J 2005; 69: 471 - 474)

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Background Hyperhomocysteinemia induces vascular endothelial dysfunction, contributing to a predisposition to the onset and/or progression of atherosclerosis. The major mechanism suggested for the adverse effect of homocysteine on vascular function seems to involve oxidative stress. Thus, we hypothesized that the administration of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin, which is experimentally demonstrated to have antioxidative properties as one of its pleiotropic effects, is a useful strategy for eliminating the detrimental events induced by hyperhomocysteinemia. Methods and Results In diet-induced hyperhomocysteinemic rats, we estimated oxidative stress and assessed endothelium-dependent vasodilatation. Hyperhomocysteinemia induced significant increases in urinary 8-isoprostaglandin F2α-III excretion and vascular superoxide generation, and impaired endothelium-dependent vasodilatation. Additional oral administration of the antioxidant fluvastatin or vitamin E, which normalized increased oxidative stress induced by hyperhomocysteinemia, ameliorated endothelial dysfunction. Conclusions Hyperhomocysteinemia, even mild to moderate, induces endothelial dysfunction through its oxidative effect. The antioxidant fluvastatin was able to cancel out the oxidative stress induced by hyperhomocysteinemia and ameliorate endothelial dysfunction. Clinical use of fluvastatin might be a potent strategy for eliminating the detrimental events induced by hyperhomocysteinemia as well as hyperlipidemia. In addition to lowering homocysteine by means of folate supplementation, administration of the antioxidants is expected to be a potentially effective anti-homocysteine therapy. (Circ J 2005; 69: 475 - 480)

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Background We investigated the mechanism of in-stent restenosis in radius stents in comparison to balloon-expandable stent (NIR stent) in pigs, with a focus on extracellular matrix (ECM). Methods and Results Radius (n=4) or NIR (n=4) stents were implanted in the left coronary arteries of miniature pigs. Quantitative coronary ultrasound (QCU) was performed before, immediately after, and at 1 and 4 weeks after the implantation. The stented-coronary arteries were harvested at 4 weeks after the implantation followed by immunohistochemical, histological, reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR studies. In QCU, mean luminal areas at 4 weeks did not differ between both groups, whereas the mean stent area and neointimal area were significantly greater in the radius (p<0.01). The immunohistochemical study revealed a significantly decreased number of neointimal macrophages and neovascularizations (p<0.05, p<0.01, respectively), and a stronger expression of tenascin-C in the radius. The histological study showed a larger ECM area and less neointimal cell density in the radius than in the NIR. The RT-PCR and real-time PCR analysis revealed an enhanced expression of tanascin-C mRNA in the radius than in the NIR. Conclusions Increased production of ECM, especially tenascin-C, played a greater role in the neointimal formation in the radius stent than inflammation. (Circ J 2005; 69: 481 - 487)

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Background A mechanism underlying the benefits of transmyocardial laser revascularization (TMLR) has been presumed to be improvement in perfusion. We evaluated myocardial blood flow around a laser channel using digital radiography combined with a ³H-labeled desmethylimipramine ([³H]DMI) deposition. Methods and Results A laser channel was created in the left ventricular wall using a YAG-laser in 6 non-ischemic rabbit hearts. After 8 weeks, [³H]DMI(1.11 MBq) was injected into the left atrium and the TMLR-treated myocardium was sectioned. Another 6 hearts were examined as controls. We measured [³H]DMI density in arbitrary units with digital radiography in the channel remnant, the surrounding area and a remote area. Flow distribution was quantified by the coefficient of variation of flows (CV). The surrounding area had the highest density (p<0.001) and the lowest CV (p<0.001), and had higher density (p<0.001) and lower CV (p<0.001) than the controls. There was no transmural difference in the density in all domains. The CV increased with depth in the remote area, as well as in controls (p<0.001), but there was no transmural difference in the surrounding area. Conclusions The TMLR increases myocardial blood flow and decreases flow heterogeneity in the surrounding area. The disappearance of transmural difference in flow heterogeneity might indicate the remodeling of microcirculation to improve regional oxygen delivery. (Circ J 2005; 69: 488 - 492)

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Background Parasympathetic drive is attenuated in heart failure, and resulting autonomic imbalance may increase the risk of sudden cardiac death. The anatomic site(s) and molecular mechanisms underlying this parasympathetic withdrawal are unknown. Methods and Results We examined the effects of pre- and post-ganglionic vagal nerve stimulation (VS) and acetylcholine (ACh) application on the heart rate of rats with right-sided congestive heart failure (CHF) induced by monocrotaline. Heart rate reduction in response to pre-ganglionic VS in CHF rats in vivo was significantly less than in controls. The suppression of spontaneous beating of isolated right atria including the whole sinoatrial (SA) node in response to post-ganglionic VS was significantly attenuated in CHF rats as well. In contrast, ACh application to the right atria resulted in a significantly larger suppression of spontaneous beating in CHF rats than controls. Proteins of neuronal nitric oxide synthase (nNOS) in the right atria were significantly decreased, whereas muscarinic (M₂) receptor was significantly increased in CHF rats compared with controls. Conclusions Both pre-and post-ganglionic vagal nerve functions are diminished in CHF rats, whereas M₂ receptor-mediated regulation of the SA node is upregulated. Downregulation of nNOS may be involved in this parasympathetic withdrawal. (Circ J 2005; 69: 493 - 499)

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Involvement of the pulmonary arteries is common in systemic Takayasu's arteritis, but pulmonary arteritis alone is very rare. A 67-year-old woman had severe right pulmonary artery stenosis and left pulmonary arterial obstruction caused by Takayasu's arteritis. Surgical treatment was successfully performed with extracorporeal circulation, without transection of the ascending aorta and the right pulmonary artery was enlarged with an autologous pericardial patch. (Circ J 2005; 69: 500 - 502)

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A vascular manifestation of von Recklinghausen's disease is rare, but may be fatal if it is disrupted. A 39-year-old male with von Recklinghausen's disease presented with a large and tender bruise extending from his left neck to his left shoulder and arm. Computerized axial tomography revealed a ruptured aneurysm of the left subclavian artery. The patient underwent emergency surgery to exclude the aneurysm, and cross-over bypass grafting of both subclavian arteries was performed. We present a brief review of vascular maintestation of von Recklinghausen's disease, as well as a discussion regarding the strategy for treating this rare presentation. (Circ J 2005; 69: 503 - 506)

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Some patients cannot undergo coronary angiography (CAG) because of the adverse effects of contrast media. In the present study gadolinium, (gadodiamide hydrate: Gd DTPA-BMA) commonly used for magnetic resonance imaging (MRI), was used as the contrast agent for diagnostic CAG in 3 patients with severe allergy to iodine or iodinated contrast agents. The indications for CAG were recurrent chest pain, evaluation of peri-operative risk of gastric cancer and abdominal aortic aneurysm, and evaluation of graft patency after coronary artery bypass grafting. The procedure was well tolerated by each patient and the amount of the gadolinium-based contrast media did not exceed 40 ml, which is twice the volume used for MRI. The images were of fair quality. In patients with allergy to iodinated contrast media, CAG with gadolinium-based contrast media is an alternative technique for evaluating coronary artery disease. (Circ J 2005; 69: 507 - 509)

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Hemodynamic deterioration because of worsening of mitral regurgitation can occur in a small number of patients undergoing atrioventricular node (AVN) ablation and pacing therapy. Patients with moderate mitral regurgitation before ablation seem prone to this complication. Successful permanent His-bundle pacing after AVN ablation was performed in a patient with chronic atrial fibrillation and moderate mitral regurgitation. Pulmonary capillary wedge pressure V-wave amplitude was markedly diminished and the mitral regurgitation area, calculated from the echocardiogram, was decreased by His-bundle pacing compared with that during right ventricular outflow tract or apical pacing. (Circ J 2005; 69: 510 - 514)

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