Background Because there is insufficient evidence to support primary percutaneous coronary intervention (PPCI) as the treatment of acute myocardial infarction (AMI), this study elucidated the efficacy of PPCI according to disease severity. Methods and Results Between January 1999 and June 2001, 3,021 AMI patients were registered at Tokyo Women's Medical University and 17 affiliated institutions. Of these, 1,994 patients with ST-elevation AMI were admitted within 12 h of onset. PPCI was performed in 1,143 and 294 were treated conservatively. The 1,437 patients were grouped according to Thrombolysis In Myocardial Infarction-risk score: PPCI was performed in 59.5% of the low-risk group, 61.8% of the moderate-risk group, and 56.2% of the high-risk group. Cardiac death was the primary outcome. In the low-risk group, no significant differences were observed between PPCI and conservative therapy for 30-day and long-term cardiac mortality rates. In the moderate-risk group, the 30-day cardiac mortality rate for PPCI was significantly lower; however, no significant intergroup differences were observed for long-term cardiac mortality. In the high-risk group, 30-day and long-term cardiac mortality for PPCI were significantly more favourable than for conservative therapy (p<0.001 and p=0.0032, respectively). Conclusions Although PPCI strongly correlated with low short- and long-term cardiac mortality rates in high-risk AMI patients, no similar correlation was found in low-risk patients. (Circ J 2008; 72: 1391 - 1396)

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Background Cardiovascular medicine has undergone rapid changes in recent years, but there are insufficient reports using large cohorts regarding these changes for Japanese coronary artery disease (CAD) patients. Hence, a large-scale prospective observational study was needed. Methods and Results A total of 36,298 patients were registered over 6 periods. Patients with hypertension, hyperlipidemia, obesity, and impaired glucose tolerance increased in number, while those with old myocardial infarction (MI), smoking habit, and family history of CAD decreased. Regarding the trends in interventional procedures, stent use increased in both the whole cohort and the acute MI subgroup, while the use of only medical control decreased. Regarding prescription trends, angiotensin-receptor blockers increased while nitrates decreased. Conclusions In a period of 3.5 years, significant changes were observed for both interventional procedures and medication, which might be related to the well-timed compliance of physicians with published evidence. However, these changes were not related to changes in the event rates, at least over the short term. Although careful attention should be paid in interpreting the results, because this is an observational study and the background of patients in each cohort might have been heterogeneous, such investigations should be constantly conducted for evidence-based practice. (Circ J 2008; 72: 1397 - 1402)

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Background The aim of this study was to assess the impact of more aggressive pharmacological treatment on short-term clinical outcomes in patients with acute non ST-segment elevation myocardial infarction (NSTEMI) who do not undergo percutaneous coronary intervention (PCI). Methods and Results The 924 NSTEMI patients treated with early conservative strategy (69.2±12.5 years, 637 males) in 50 hospitals that were high-volume centers with facilities for primary PCI were recruited to the Korean Acute Myocardial Infarction Registry (KAMIR) from November 2005 to August 2007. For all patients, the pharmacotherapy index based on the use of drugs during hospital stay was assessed (range of points 0-10). Primary endpoint was the combined in-hospital mortality and morbidity and major adverse cardiac events during 1 month of clinical follow-up. Of the patients, data from 847 who were followed-up for 1 month after discharge were analyzed. The rate of the primary endpoint decreased with an increase of the pharmacotherapy index and this result was similar in the low- and high-risk groups. In the multivariate analysis, low pharmacotherapy index (≤4 points) was an independent predictor of the primary endpoint. Conclusions More intensive pharmacological treatment may improve short-term clinical outcomes in acute NSETMI patients who do not undergo PCI. (Circ J 2008; 72: 1403 - 1409)

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Background The aim of the present study was to evaluate the relationship between clinical outcomes after acute myocardial infarction (MI) and renal function by glomerular filtration rate (GFR) in patients with normal or mildly elevated serum creatinine concentrations. Methods and Results As part of the Korean Acute Myocardial Infarction Registry (KAMIR), 6,834 acute MI patients with a serum creatinine concentration of ≤2.0 mg/dl were enrolled from November 2005 to December 2006. The renal function was stratified arbitrary to 5 groups: (1) normal function, >90.0; (2) preserved function, 75.0-89.9; (3) mild dysfunction, 60.0-74.9; (4) moderate dysfunction, 45.0-59.9; (5) severe dysfunction, <45 ml · min^-1 · 1.73 m^-2. Clinical characteristics, mortality and adverse events were analyzed among each group. Although reperfusion and medical therapies were underused, the rates of mortality and adverse events were increased with declining renal function. After adjustment with confounders, severe and moderate renal dysfunctions were important risk predictors of in-hospital mortality, long-term mortality and adverse events. Conclusion The spectrum of renal function, when it was presented by GFR, is broad and is an important risk predictor for adverse outcomes after acute MI, even in patients with normal or mildly elevated serum creatinine concentrations. Furthermore, standard treatments were underused in any degree of renal dysfunction. (Circ J 2008; 72: 1410 - 1418)

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Background To evaluate the association between components of metabolic syndrome (MS) and ischemic heart disease (IHD) in Taiwanese patients with type 2 diabetes mellitus (T2DM). Methods and Results A total of 1,296 (604 men and 692 women) subjects with T2DM aged 62.5±11.7 (14-87) years were studied. MS was defined using the World Health Organization modified criteria and included more than 2 of hypertension, obesity, dyslipidemia and microalbuminuria. IHD was diagnosed through history or ischemic electrocardiogram according to the Minnesota codes. Results showed that MS was present in 76.2% and IHD in 36.3% of the patients, respectively. MS increased with age for both sexes, but there was no difference between men and women in the age groups of <45, 45-54 and 55-64 years. However, the prevalence of MS was significantly higher in women (87.7% vs 78.0%) in the age group ≥65 years. IHD prevalence was significantly higher in patients with MS, hypertension, dyslipidemia and obesity (p<0.01), and was higher with borderline significance for microalbuminuria (0.05<p<0.1). The respective age-adjusted odds ratios were 3.61 (2.57-5.08), 7.10 (5.38-9.38), 1.70 (1.32-2.18), 1.75 (1.33-2.28), and 1.11 (0.88-1.41). Conclusions The prevalence of MS in subjects with T2DM is high and increases with age. The impact of different risk factors on IHD is diverse, with hypertension being the most important. (Circ J 2008; 72: 1419 - 1424)

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Background Intravenous nicorandil infusion with percutaneous coronary intervention (PCI) has been reported to reduce reperfusion injury events and improve cardiac function in patients with acute myocardial infarction (MI). However, there is limited information on the use of intracoronary nicorandil. Methods and Results In the present study, 73 patients with acute ST segment elevation MI undergoing PCI were randomly assigned to the Nicorandil Group (n=37) or the Control Group (n=36). The composite endpoints were the incidences of ventricular arrhythmia, no-reflow and slow flow. A significant difference in the composite endpoint was observed in the Nicorandil Group when compared with the Control Group (p=0.037). The occurrence of post Thrombolysis In Myocardial Infarction (TIMI) grade 3 was significantly higher in the Nicorandil Group (p=0.019). Major adverse cardiac events during hospitalization and within 30 days of treatment were similar between the 2 groups. Conclusion Administration of intracoronary nicorandil reduced the occurrence of no-reflow, slow reflow, and reperfusion arrhythmia, and improved the myocardial perfusion grade, TIMI flow during PCI and improved clinical outcomes in patients with acute MI. (Circ J 2008; 72: 1425 - 1429)

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Background The efficacy of sirolimus-eluting stents (SESs) has not been established in dialysis patients. Methods and Results This study was a non-randomized observational single-center registry in a community hospital: data for 80 consecutive dialysis patients who underwent percutaneous coronary intervention (PCI) with SES were compared with those of a historical group of consecutive 124 dialysis patients treated with bare-metal stents (BMS). After 1 year, the cumulative incidence of major adverse cardiac events (MACE), comprising cardiac death, nonfatal myocardial infarction, stent thrombosis, or target lesion revascularization (TLR), was 25.2% in the SES group and 38.2% in the BMS group (p=0.048). In multivariate analysis, use of SES remained an independent predictor of MACE at 1 year after PCI (risk ratio 0.70, 95% confidence interval 0.52-0.93, p=0.015). Rates of TLR were 21.7% in the SES group and 30.9% in the BMS group and (p=0.15). Subgroup analysis showed that use of SES was effective in patients with small vessels, non-diabetic patients, and patients without highly calcified lesions. Conclusions In dialysis patients, the implantation of SES was moderately effective in reducing MACE at 1 year after PCI as compared with BMS. However, the TLR rate at 1 year was relatively higher than previously reported. (Circ J 2008; 72: 1430 - 1435)

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Background The impact of isolated diastolic dysfunction (IDD) and systolic dysfunction (SD) on health-related quality of life (HRQOL) is unknown. Methods and Results To evaluate HRQOL in patients with IDD and SD under treatment, information on outpatients aged 60-84 years was extracted from the records of 4,500 consecutive individuals who underwent echocardiographic examination at Sado General Hospital. The medical records of these patients were reviewed and a questionnaire, including the Medical Outcome Study Short Form 36, was mailed to 71 IDD and 99 SD patients; answers were obtained from 66 and 91 patients, respectively. The HRQOL of patients with cardiac dysfunction was impaired even when echocardiographic parameters improved with treatment. Patients with IDD showed an impairment of HRQOL similar to those with SD. Compared with males, female patients had a larger and more significant reduction in the physical and mental components of the HRQOL score. These scores correlated positively with exercise capacity in patients with IDD or SD. Conclusions Impaired HRQOL, in both its mental and physical components, is a serious problem for IDD and SD patients under treatment. Because exercise intolerance may underlie the reduced HRQOL, improving exercise capacity could be an important target for managing outpatients with heart failure. (Circ J 2008; 72: 1436 - 1442)

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Background Because the ratio of mitral inflow and annular velocity to stroke volume has been reported as an index of diastolic elastance (Ed), the hypothesis tested in the present study was that Ed during exercise would be more abnormal in female than in male patients with type 2 diabetes. Methods and Results Ed was measured at rest and during graded supine bicycle exercise (25W, 3-min increments) in 53 patients (27 males, mean age 53±14 years) with type 2 diabetes and 53 age- and gender-matched controls. The patients with diabetes were divided into 2 groups by gender. Ed was not significantly different at rest between men and women, but was significantly higher during exercise in women than in men (25 W, 0.15±0.04 vs 0.20±0.07, p=0.009; 50 W, 0.16±0.05 vs 0.21±0.08, p=0.0175). Conclusion Left ventricular (LV) diastolic elastance is abnormal during exercise, but not at rest, in patients with diabetes without overt heart disease. Female gender was associated with increased LV stiffness during exercise among patients with type 2 diabetes. (Circ J 2008; 72: 1443 - 1448)

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Background The aim of this study was to determine whether the extent of late gadolinium enhancement (LGE) is associated with left ventricular (LV) function in patients with hypertrophic cardiomyopathy (HCM). Methods and Results Forty-seven patients with HCM (35 males, mean age 53±14, 14 with LV outflow tract obstruction) underwent cardiovascular magnetic resonance imaging and comprehensive echocardiographic examination. The extent of LGE was expressed as LGE volume and LGE percentage of LV volume. LGE was present in 40 (85.1%) of 47 patients. The mean LGE volume was 36.5±36 cm³, and the mean percentage of LV volume was 16.4±17%. Following adjustment for age, mitral regurgitation and LV mass index, LGE volume and percentage positively correlated with the left atrial volume index (r=0.388, p=0.009 and r=0.425, p=0.004, respectively). However, there was no significant association of functional class, ejection fraction, mitral flow, or annular velocities with the extent of LGE. Conclusions In HCM patients, the extent of LGE positively correlated with the left atrial volume index, a surrogate marker of chronic diastolic burden. These findings suggest that myocardial scarring may be a pathologic substrate for chronic diastolic dysfunction in patients with HCM. (Circ J 2008; 72: 1449 - 1453)

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Background The main pulmonary arterial (PA) distensibility in patients with pulmonary hypertension (PH) and pulmonary embolism (PE) is uncertain. Methods and Results We enrolled 45 patients with echocardiographic signs of PH and without imaging evidence of PE, and another 45 who were found by multidetector-row computed tomography to have PE. Fifty normal patients served as a control group. The PA distensibility was calculated from the change in main PA diameter between diastole and systole, as the maximal systolic diameter minus the minimal diastolic diameter divided by the minimal diastolic diameter. The PA distensibility is lowest in PH (6.0±2.7%), followed by PE (12.9±3.4%) and then the normal controls (25.9±5.7%). Statistical analysis of data obtained from patients with PE or PH reveals that a PA distensibility of >8.3% could be used to identify PE with a sensitivity of 83% and a specificity of 82%. After a 3-month anticoagulation, 22 of 45 PE patients had complete resolution of thrombus; 23 had residual thrombus. The PE patients, regardless of residual thrombus presence, had significant improvement of PA distensibility after a 3-month anticoagulation, although the diameters of main PA did not shrink. Conclusion PA distensibility is a method to distinguish acute PE from chronic PH. (Circ J 2008; 72: 1454 - 1459)

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Background Pulmonary vein (PV) stenosis is a major complication of PV isolation (PVI) by catheter ablation, so in the present study the optimal position for detecting PV stenosis on enhanced multidetector computed tomography (MDCT) image acquisition was determined. Methods and Results The 64-slice enhanced MDCT was carried out before and after PVI in 116 consecutive patients with atrial fibrillation while they were in the prone position, as well as while supine. The supine position MDCT image showed >50% diameter stenosis of the PV in 11 (9%) patients before PVI (% diameter stenosis: mean 55±4%, range 51-65%). Greater than 50% diameter stenosis was seen in the left inferior PV in all 11 patients. The prone position attenuated the PV stenosis findings in the MDCT images in all 11 patients (mean 9±6%, range 2-18%). Stenosis visualized on images acquired in the supine position was, therefore, concluded to be pseudostenosis caused by descending aorta compression. At 3 months after PVI, no significant changes in PV diameter were observed in these 11 patients. Conclusion The present study demonstrated that the prone position is essential for eliminating PV pseudostenosis observed on supine-position enhanced MDCT images. The results also indicate that preexisting PV organic stenosis is rare. (Circ J 2008; 72: 1460 - 1464)

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Background This study evaluated the usefulness of 3-dimensional echocardiography (3-DE) for identifying permanent pacemaker (PPM) or implantable cardioverter defibrillator (ICD) lead-related symptomatic tricuspid regurgitation (TR). Methods and Results Eighty-seven patients underwent 3-DE examination: 50 patients with PPM, 17 with ICD, and 20 with cardiac resynchronization therapy devices. TR severity was classified as trivial/mild, moderate, or severe according to the ratio of TR area to right atrium area. The 3-DE identified the lead route and position at the tricuspid valve in 82 patients (94.2%). In 5 patients, images without lead-induced artifacts could not be obtained. TR severity was trivial/mild in 50 patients, moderate in 20 patients, and severe in 12 patients. In all patients with trivial/mild TR and all but 1 patient with moderate TR, leads were positioned on the annulus side between leaflets. Lead-induced obstruction to tricuspid valve closing was identified in 1 patient with moderate TR and in 7 of 12 patients with severe TR: 4 patients had septal leaflet obstruction, and 4 had posterior leaflet obstruction. Conclusions The 3-DE can identify the lead route and position at the tricuspid valve and lead-related severe TR, so may be a useful technique of diagnosing the cause of severe TR in patients with PPM or ICD. (Circ J 2008; 72: 1465 - 1470)

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Background The therapeutic strategy for pulmonary atresia (PA) and severe pulmonary stenosis (PS) with intact ventricular septum is controversial. Recent improvements in prenatal detection necessitate the identification of predictors of outcome for appropriate counseling and prenatal management planning. Methods and Results Echocardiograms of 18 fetuses antenatally diagnosed with PA (n=14) and PS (n=4) were reviewed and the total cardiac dimension (TCD) and tricuspid valve diameter (TVD) were measured. The right ventricular end-diastolic volume (RVEDV) was calculated from the right ventriculogram of the neonatal period by the percentage of the predicted normal value (%RVEDV). There was a positive correlation between TVD/TCD and %RVEDV (p<0.001). As the initial treatment, balloon atrioseptostomy was performed in 13 cases of TVD/TCD <0.26. As the final treatment, patients with TVD/TCD <0.17 underwent or were planned for the Fontan procedure. Patients with TVD/TCD >0.21 underwent or were planned for biventricular repair. Patients whose TVD/TCD was between 0.17and 0.21 underwent or were planned for 1.5 ventricular repairs. Conclusion TVD/TCD is a useful index for selecting the postnatal initial treatment for PA/PS and to predict the final status of the fetus. Prenatal detection and prediction of the future status is helpful for family counseling. Furthermore, it will help to decide the postnatal management prenatally. (Circ J 2008; 72: 1471 - 1475)

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Background The purpose of the present study was to evaluate the effect of modified ultrafiltration (MUF) on neonates with transposition of the great arteries (TGA) undergoing arterial switch operation. Methods and Results The current study included 36 neonates who underwent an arterial switch operation between 1998 and 2006. Arterio-venous MUF was done in 15 patients (MUF-treated group) and the other 21 patients were controls. Parameters included hematocrit, hemodynamics, pulmonary function, drain loss, leak of peritoneal fluid, length of intubation, and intensive care unit (ICU) stay. The hematocrit increased from 34±2% to 47±4% in the MUF-treated group. Blood pressure in the MUF-treated group was significantly increased without any change of central venous or left atrial pressure. Post-operative oxygenation in the MUF-treated group was greater than that of the control group (P/F ratio: 258±92 vs 170±100 mmHg, p<0.05), which did not contribute to decrease in intubation time (54±33 vs 52±29 h, p=NS). Post-operative chest drain loss and peritoneal fluid leak were comparable. The ICU stay in the MUF-treated group was significantly shorter than that in the controls (101±34 vs 139±42 h, p<0.05). Conclusions MUF brought improvement in blood pressure and gas exchange capacity and subsequent shorter ICU stay. MUF did not have significant impact on intubation time and capillary leak. (Circ J 2008; 72: 1476 - 1480)

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Background Metabolic syndrome (MetS) is a risk factor for cardiovascular disease and mortality, but, the relationship between MetS and survival after coronary artery bypass grafting (CABG) remains unclear. Methods and Results The outcomes of patients with and without MetS were analyzed. Patients who had undergone CABG at Juntendo University Hospital between January 1984 and December 1992 were enrolled. The survival search was performed by the end of 2000. The patients were categorized by the existence of preoperative MetS using the modified American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) definition with body mass index instead of waist circumference. MetS was present in 551 (46.6%) patients and absent in 632 (53.4%). Preoperative MetS was associated with long-term poor prognosis in terms of all-cause death (hazard ratio (HR) 1.34; 95% confidence interval (CI) 1.03-1.74; p=0.028) and cardiac death (HR 2.31; 95% CI 1.36-3.92; p=0.002) in non-diabetic patients. These differences in the mortality of the 2 groups were more obvious after 10 years. However, among the patients with diabetes, the presence of MetS was not related to long-term mortality. Conclusions Preoperative MetS predicted increased all-cause and cardiac mortality, especially after 10 years, in non-diabetic patients undergoing CABG. (Circ J 2008; 72: 1481 - 1486)

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Background The purpose of this study was to investigate the follow-up results of perimembranous ventricular septal defect (VSD) with left ventricular to right atrial (LV-RA) shunt since infancy and to analyze the morphologic variations of this shunt. Methods and Results The study group comprised 232 consecutive pediatric patients with isolated perimembranous VSD and aneurysm, of whom 134 (58%) had LV-RA shunts. Follow-up echocardiography was performed to assess for the size of both the VSD and LV-RA shunt. There were no significant differences between groups in terms of sex, age at the initial echocardiography, follow-up period, number of patients with tricuspid regurgitation, and initial VSD size. There was a significant difference between groups in spontaneous closure (p=0.039). The event-free probability (no surgical repair of the defect) was not significantly different between the groups (p=0.129). Conclusions Perimembranous VSD with LV-RA shunt in infancy is common and associated with less chance of spontaneous closure. Color Doppler echocardiography can greatly improves the diagnostic efficacy and assist in understanding the mechanisms leading to this particular anomaly. (Circ J 2008; 72: 1487 - 1491)

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Background The etiologic agent of Kawasaki disease (KD) is unknown, but may be dengue infection because of reported cases of concomitant KD and dengue. Methods and Results Prospective study was conducted to ascertain the relationship of positive serology for dengue infection in pediatric patients presenting with KD. A total of 65 cases were diagnosed with KD during the period of 4 years and of the 48 who had a complete dengue serologic study, 9 had a positive dengue titer. Conclusion In the present study 18.7% of patients had proven dengue infection from a positive serologic study. Further case-control study with other pediatric patients presenting with acute febrile illness needs to be done to support this significant finding. (Circ J 2008; 72: 1492 - 1494)

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Background The relationship between the level of amputation and the activities of daily living (ADL) in Japanese patients with arteriosclerosis obliterans (ASO) is unclear. Methods and Results In the present study 81 patients with ASO who underwent lower extremity amputation and were discharged from hospital after rehabilitation we evaluated. The patients were classified into 4 groups: toe amputation group (Toe), heel-preserving amputation group (Heel), below-knee amputation group (BK), and above-knee amputation group (AK). ADL at discharge and factors affecting the length of hospitalization were determined. Patients were walking at discharge in 94.5%, 94.0%, 59.0%, and 0.0% of the Toe, the Heel, BK, and AK group, respectively. However, the ratio of patients able to walk independently was 68% in the Toe group and 19% in the Heel group. In addition, the length of hospital stay was significant shorter in the Toe group than in the other groups. Factors affecting the length of hospital stay were the amputation level, cerebrovascular disease, reoperation, and diabetes. Conclusions ADL are less affected and the length of hospital stay is shorter for patients undergoing toe amputation than other levels of lower extremity amputation. However, heel-preserving amputation maintains a comparable level of ADL in terms of ambulatory discharge. (Circ J 2008; 72: 1495 - 1498)

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Background Contrast-induced nephropathy (CIN) frequently complicates cardiac catheterization, so the objectives of present study were to investigate the usefulness of cystatin C before catheterization and establish a cut-off level for CIN, and to examine the changes in cystatin C and several other markers in patients with and without CIN. Methods and Results Prospective study of consecutive 87 patients who underwent elective catheterization: moderate renal disease defined as glomerular filtration rate 30-59 ml · min^-1 ·1.73 mm^-2; cystatin C and creatinine (Cr), urinary liver-type fatty acid-binding protein (L-FABP), α₁, β₂ microglobulins, N-acetyl-β-D-glucosaminidase, and microalbumin were measured immediately before, and 1, 2, and 3 days after catheterization. CIN occurred in 18 patients and receiver-operating characteristic analysis showed a higher area-under-the-curve for cystatin C compared with serum Cr (0.933 vs 0.832 p=0.012). At a cut-off level of >1.2 mg/L, cystatin C before catheterization exhibited 94.7% (95% confidence interval: 0.851-1.015) sensitivity and 84.8% specificity for detecting CIN. Cystatin C levels were higher in CIN patients than in those without CIN, even before catheterization (cystatin C: 1.08±0.22 vs 1.36±0.28 mg/L, p=0.007). Urinary L-FABP was increased on days 1 and 2 in patients with moderate renal disease. Conclusion Cystatin C was useful for predicting the occurrence of CIN. Urinary L-FABP was the only marker of transient renotubular damage. (Circ J 2008; 72: 1499 - 1505)

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Background Doxorubicin (Dox) depletes p300 from cardiac myocytes and induces apoptosis of these cells. p300 protein possesses ubiquitin ligase activity for the p53 tumor suppressor gene product, catalyzes p53 polyubiqutination, and facilitates p53 degradation in an ubiquitin-dependent manner. The present study investigated the ubiquitin-dependent regulation of p53 by Dox and p300 in cardiac myocytes. Methods and Results Primary cardiac myocytes from neonatal rats were exposed to a proteasome inhibitor, MG132, in culture. MG132 increased both p300 and p53 protein levels in these cells, suggesting that ubiquitin-dependent degradation is involved in the homeostasis of these proteins. Notably, treatment of cardiac myocytes with Dox decreased the protein levels of p300 but markedly increased those of p53. By immunoprecipitation-Western blotting, it was shown that treatment with Dox decreased poly-ubiquitinated p53 but increased that of p300 in cardiac myocytes. Finally, the overexpression of p300 in cardiomyocytes suppressed the Dox-mediated increase in the p53 level in addition to inhibiting Dox-induced apoptosis. Conclusion Dox reciprocally regulates p300 and p53 through ubiquitin-dependent pathways and that p300, by its ubiquitin ligase activity, is partially involved in the ubiquitin-dependent degradation of p53 in cardiac myocytes. (Circ J 2008; 72: 1506 - 1511)

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Background Reactive oxygen species (ROS) is deeply involved in the process of ventricular remodeling after myocardial infarction (MI). Under oxidative stress, endothelial nitric oxide synthase (eNOS) can be converted to a ROS generator, because a relative lack of tetrahydrobiopterin (BH4), an essential cofactor for NO synthesis, leads to eNOS uncoupling. The uncoupled eNOS generates superoxide rather than NO. The possible role of ROS generated by eNOS in ventricular remodeling after MI was investigated. Methods and Results Rats were treated with oral BH4 supplementation starting at 3 days before coronary artery ligation. At 4 weeks after MI, there was augmented superoxide production in association with reduced BH4/dihydrobiopterin (BH2) ratio and eNOS dimer/monomer protein ratio in the heart. Treatment with BH4 increased BH4/BH2 ratio and eNOS dimer/monomer ratio, and decreased superoxide production. In BH4-treated MI rats, left ventricular size was smaller, thickness of the non-infarcted posterior wall was thinner, and cardiac function was preserved compared with the control MI rats. Conclusions The present study suggested that ventricular remodeling process after MI leads to BH4 oxidation and resulted in uncoupled eNOS-derived superoxide generation, which further augmented the remodeling process and deteriorated cardiac function. (Circ J 2008; 72: 1512 - 1519)

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Background The time course of oxidative stress involving nitric oxide (NO) after myocardial ischemia reperfusion (MIR) has not been elucidated in detail, so the present study was designed to assess the dynamics of oxidative stress after MIR, urinary excretion of oxidized bilirubin metabolites (ie, biopyrrins) and their generation in various organs. Methods and Results Rat models of MIR were created by occluding the left coronary artery for 30 min followed by 48 h of reperfusion. Levels of urinary biopyrrins increased biphasically at 8 h and 24 h after MIR. Biopyrrins were upregulated in the lungs at 8 h after MIR, according to immunohistochemistry and ELISA, and at 24 h biopyrrin expression was increased in the heart and lungs. The NO synthase inhibitor, N^G-monomethyl-L-arginine, significantly diminished biopyrrin synthesis in the heart and lungs at 24 h, but not in the lungs at 8 h after MIR. Hemodynamic assessment revealed increased left ventricle end-diastolic pressure, suggesting that lung congestion influences pulmonary biopyrrin formation. Conclusions The dynamics of urinary biopyrrins might reflect earlier biopyrrin generation in the lungs and delayed formation in both the lungs and heart when NO is involved. Therefore, urinary biopyrrins can serve as a useful marker of systemic oxidative stress after MIR. (Circ J 2008; 72: 1520 - 1527)

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Background Recent studies have revealed that bone marrow cell (BMC) transplantation is effective not only for myocardial infarction (MI), but also for dilated cardiomyopathy (DCM). However, the method of administering donor cells remains unknown, and may differ between MI and DCM. In the present study, intramyocardial (IM) injection and intravenous (IV) delivery of BMC were compared in each etiological model. Methods and Results MI was induced in 72 mice and DCM in another 36 mice by doxorubicin. BMCs were administered IV or IM in an acute MI (AMI), old MI (OMI) or DCM model. In the AMI model, left ventricular (LV) remodeling was reduced in both the IM- and IV-groups, but only in the IM-group in the OMI model. In the DCM model, the LV dimension of the IV-group was smaller than that of the IM-group. Histological examination showed that green fluorescent protein (GFP) cells were equally distributed in the infarct area of the IV- and IM-groups in AMI, and in the IM-group in the OMI model. In the DCM model, GFP cells were diffusely scattered throughout the ventricular wall in the IV-group, but were confined to the injection site in the IM-group. Conclusions In OMI, IM delivery of BMCs was more effective than IV; however, IV delivery was superior in DCM. Delivery route should be selected according to the etiology of heart disease to optimize the efficacy of BMC transplantation. (Circ J 2008; 72: 1528 - 1535)

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Background Because optical coherence tomography (OCT) requires balloon-occlusion to overcome image attenuation by blood, the present study investigated the safety and usefulness of a new non-occlusive technique. Methods and Results The 40 angina patients were assigned to the continuous-flushing method or the balloon-occlusion method group. The continuous-flushing method was superior for observing proximal lesions compared with the balloon-occlusion method (94% vs 55%, p=0.01). There were no differences between groups in the visible length and image quality. There were no major complications during OCT. Conclusions The continuous-flushing method is safe and useful for OCT. (Circ J 2008; 72: 1536 -1537)

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Background The intermediate filament protein, nestin, may play a role in tissue regeneration and nestin expression has been detected in coronary atherosclerotic plaques. To date, no population-based studies concerning the role of the nestin gene in coronary heart disease (CHD) have been reported. Methods and Results The 3 SNPs in the nestin gene were genotyped in 1,494 individuals from 580 Irish families. rs11582300 and rs3748570 were associated with early-onset CHD (p=0.04 and p=0.02). Conclusion Nestin gene variants are associated with early-onset CHD. Further research on nestin's role in atherosclerosis is required. (Circ J 2008; 72: 1538 - 1539)

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The patient was a 73-year-old female who developed chest pain and dyspnea 16 days after her husband passed away. ST segment elevation was detected on V_2-5 by electrocardiography and emergency coronary arteriography was done for suspected acute myocardial infarction. No coronary arterial stenosis was present and ventricular septal perforation and takotsubo cardiomyopathy were diagnosed by left ventriculography. The perforation was closed and the patient was discharged 23 days after surgery. This patient had a very rare case of takotsubo cardiomyopathy, which was complicated by ventricular septal perforation and was saved by surgical treatment. (Circ J 2008; 72: 1540 - 1543)

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Congenital atresia or extreme hypoplasia of individual pulmonary veins is a rare condition that is usually asymptomatic if it only involves 1 or 2 segments of the lungs. It may be fatal if it occurs in combination with other complex cardiac defects. The patients often present with recurrent pulmonary infections, hemoptysis, or cyanosis in the latter case. A definitive diagnosis can be made by cardiac catheterization with selective pulmonary wedge angiography. The treatment of this condition is a challenge and is controversial, and the prognosis is usually poor. We describe the case of a male infant who suffered from shortness of breath and cyanosis since birth. On echocardiography and cardiac catheterization, he was found to have a complex congenital heart disease with a single ventricle (right ventricle morphology), mitral atresia, large atrial septal defect, and atresia of the right pulmonary veins; severe pulmonary hypertension was also observed. He underwent pulmonary artery banding at the age of 2.5 months, but he died because of a pulmonary infection at the age of 6 months. In this report, we present this rare case and review the previous literature. (Circ J 2008; 72: 1544 - 1546)

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A 61-year-old man, who had suffered congestive heart failure following a large transmural acute myocardial infarction (AMI) of the anterior wall, developed a mobile ball-like thrombus in the left ventricle (LV). On the third day after onset of AMI, when the patient had recovered slightly from congestive heart failure, we performed coronary artery bypass grafting and LV thrombectomy, then the fragile LV wall was successfully repaired using the infarction exclusion technique (David-Komeda procedure). (Circ J 2008; 72: 1547 - 1549)

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Mediastinal radiation therapy can cause progressive fibrosis and might, as a result, induce various cardiac problems. We encountered a patient who presented with recurrent syncope 20 years after radiation therapy for breast cancer. She had multiple cardiac problems including bilateral coronary ostial stenoses, pre-valvular right ventricular outflow tract stenosis, and constrictive pericarditis. The cause of syncope was paroxysmal atrioventricular block (an 18-s long pause recorded by the implantable loop recorder). The patient was treated by the implantation of a pacemaker and did not experience syncope during 9 months of follow up. (Circ J 2008; 72: 1550 - 1552)

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