Background Actual data regarding coronary artery disease (CAD) patients in Japan is scarce, so in the present study a large database of Japanese patients with significant CAD was constructed for analysis of the relationship between medical treatments and outcomes in this cohort. Methods and Results The present study enrolled 15,628 patients who underwent coronary angiography and were diagnosed as having significant stenosis in at least 1 coronary artery. Of these, 13,812 patients were followed up and included in the analysis: 10,626 (77%) men and 3,186 (23%) women. Diagnosis at the time of registration was acute myocardial infarction (AMI) for 2,955 patients, old myocardial infarction for 3,913 patients and unstable angina pectoris for 2,049 patients. Patients were followed up for an average of 2.7 years. At the start of the follow-up, 37.4% of the patients were prescribed statins, 50.2% calcium-channel blockers (CCB), 31.6% angiotensin-converting enzyme inhibitors (ACEI), 13.5% angiotensin II receptor blockers (ARB) and 60.2% nitrates. Univariate Cox regression model analysis showed that the hazard ratio (HR) of statins was 0.780 (95% confidence intervals (CI), 0.710-0.856; p<0.001); fibrates, 0.580 (95%CI, 0.425-0.790; p=0.001); CCB, 1.067 (95%CI, 0.976-1.166; p=0.153); ACEI, 1.062 (95%CI, 0.968-1.166; p=0.202); ARB, 1.036 (95%CI, 0.914-1.174; p=0.581); nitrates, 1.147 (95%CI, 1.043-1.260; p=0.005). When the data were adjusted for background data and all cardiovascular medications, the HR of statins was 0.809 (95%CI, 0.726-0.901; p<0.001), CCB 1.031 (95%CI, 0.937-1.135; p=0.535), ACEI 1.023 (95%CI, 0.924-1.132; p=0.663), ARB 0.991 (95%CI, 0.867-1.132; p=0.890), nitrates 1.074 (95%CI, 0.973-1.186; p=0.155). For patients presenting with AMI at the time of registration, the HR of CCB was 1.340 (95%CI, 1.084-1.655; p=0.007) and that of nitrates was 0.862 (95%CI, 0.703-1.059; p=0.157). Conclusion In a cohort of CAD patients in Japan, the prescription pattern differed from that of Western studies. Statins and fibrates were shown to be significantly beneficial in the whole cohort. In the AMI subgroup, CCB showed a deleterious effect and nitrates showed a non-significant tendency for beneficial effect, which should be investigated in future randomized control trials. (Circ J 2007; 71: 1835 - 1840)

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Background Studies from North America indicate that patients admitted during the weekend with acute myocardial infarction (AMI) have a worse outcome than weekday-admitted patients, probably reflecting a lower rate of invasive procedures. However, it is unclear whether the same is true in Japan, which has a different healthcare system. Methods and Results Using the Japanese Acute Coronary Syndrome Study (JACSS) database, this study included 4,805 consecutive patients who were admitted within 48 h of onset of AMI (3,526 [73.4%] patients with weekday onset [Monday through Friday] and 1,279 [26.6%] with weekend onset [Saturday and Sunday]). There were no significant differences between the 2 groups in patient background and clinical features. The proportions of patients who underwent emergency catheterization (88.4% vs 88.0%) and reperfusion therapy (81.5% vs 81.4%) were also similar. There were no differences between the 2 groups in the in-hospital, 30-day, and 1-year mortality rates. Even after various adjustments, there was no difference in the risk of death associated with weekend versus weekday onset of AMI. Conclusion There were no obvious differences in outcome for Japanese AMI patients in the weekday- or weekend-onset group, suggesting the quality of the Japanese healthcare system is similar for the entire week. (Circ J 2007; 71: 1841 - 1844)

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Background It is unclear whether a marked reduction of low-density lipoprotein-cholesterol (LDL-C) in patients with coronary heart disease (CHD) and mild hypercholesterolemia leads to less progression of atherosclerosis. Methods and Results Patients with CHD and hypercholesterolemia (100<LDL-C <140 mg/dl) who underwent coronary angiography (CAG) and intravascular ultrasound (IVUS) were randomly assigned to the atorvastatin (10-20 mg/day) group or `usual care' group. After 12 months 58 patients had follow-up CAG and IVUS studies that could be evaluated. Cross-sectional areas of the vessel, lumen, and plaque were measured at 1-mm intervals, and volumetric calculations were based on Simpson's rule. After 12 months, the mean reduction of LDL-C was 34% in the atorvastatin group and 0% in the usual care group (p<0.01). The mean absolute plaque volume showed a larger increase in the usual care group than in the atorvastatin group (atorvastatin -1.4±11.6 mm³, usual care 7.6±10.3 mm³; p<0.01). Vessel volume also showed a larger increase in the usual care group than in the atorvastatin group (atorvastatin 2.2±10.9 mm³, usual care 10.9±17.7 mm³; p=0.03). Conclusions Atorvastatin treatment prevented the further progression of atherosclerosis by maintaining LDL-C below 100 mg/dl in patients with CHD and hypercholesterolemia (100<LDL-C <140 mg/dl). (Circ J 2007; 71: 1845 - 1850)

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Background The significance of dynamic changes in a depressed ST-segment in the reciprocal changes after percutaneous coronary intervention (PCI) of patients with ST-elevation myocardial infarction (STEMI) is unknown, so the aim of this study was to evaluate the significance of reciprocal ST-segment depression normalization (STN) on long-term mortality in patients with STEMI treated with primary PCI. Methods and Results Data for 247 consecutive patients with STEMI were analyzed; 84 patients were excluded because of exclusion or incomplete inclusion criteria, so finally, 163 patients successfully treated with primary PCI were included. The study group was divided into 3 subgroups according to percentage of STN: poor STN (<30%), partial STN (30-70%), complete STN (>70%). Complete STN occurred in 63%, partial in 24% and poor in 13% of patients. STN correlated with late mortality (15% vs 28% vs 38% respectively, p=0.012). Patients who died during the follow-up period had a lower mean percentage reduction of initial ST-segment depression after PCI (50% vs 75%, p=0.001). Percentage reduction of initial ST-segment depression after PCI was a significant and independent risk factor of long-term mortality (odds ratio 1.01; 95% confidence interval: 1.00-1.02; p=0.02). Conclusions These data revealed the use of reciprocal changes normalization as a novel tool for assessment of long-term risk of death in patients after successful primary PCI for STEMI. (Circ J 2007; 71: 1851 - 1856)

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Background This study tested the hypothesis that in the acute phase of myocardial infarction (MI), the circulating level of soluble CD40 ligand (sCD40L), an index of platelet activation, is predictive of angiographic morphologic features that indicate high-burden thrombus formation (HBTF) in the infarct-related artery (IRA). Methods and Results This prospective study included 162 consecutive patients: 64 with HBTF and 98 with low-burden thrombus formation (LBTF). All patients had a Killip's classification ≤3 ST-segment elevation acute myocardial infarction (AMI) of onset <12 h who were undergoing primary percutaneous coronary intervention (PCI). Blood samples for measurement of the circulating levels of sCD4L and high-sensitivity C-reactive protein (hs-CRP) and white blood cell (WBC) count were collected before PCI. The circulating levels of sCD40L and hs-CRP, and the WBC count were also evaluated in 20 normal control subjects. Blood was aspirated by export suction catheter from the intracoronary artery (ICA) in 49 HBTF patients. The WBC count, and the circulating levels of hs-CRP and sCD40L were significantly higher in the HBTF and LBTF groups than in the normal control subjects (all p<0.005). Additionally, the circulating levels of sCD40L and the WBC count were substantially higher in the HBTF than in the LBTF patients (all p<0.001). Furthermore, in HBTF patients the ICA had a significantly higher sCD40L level and WBC count compared with the values for the systemic circulation (all p<0.001). Multiple statistical analyses identified increased circulating level of sCD40L as the most independent predictor of HBTF in the IRA (p<0.0001). Conclusions The sCD40L level is the most independent predictor of angiographic morphologic features that indicate HBTF in the acute phase of MI. (Circ J 2007; 71: 1857 - 1861)

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Background In the present study 15 years of experience with surgical coronary artery bypass grafting (CABG) in patients with left ventricular (LV) dysfunction were retrospectively analyzed. Methods and Results Between August 1990 and May 2005, a total of 120 patients with severe LV dysfunction (LV ejection fraction (EF) ≤30%) caused by coronary artery disease underwent CABG (mean age 60.3 years, 94 males) Among the 120 patients, 102 had 3-vessel or left main disease. Mean LVEF was 23.5%, and 75% of patients were New York Heart Association functional class III or IV. CABG was performed in all patients with a mean of 2.9 distal grafts/patient. There were 13 hospital deaths (11%). Mean LVEF improved to 32% postoperatively, and further improved to 39% at a mean follow-up of 57.6 months (p<0.05). During the follow-up period, 2 cardiac-related deaths occurred. Kaplan-Meier survival rates at 1, 5 and 10 years were 87.7%, 80.9%, and 44.4%, respectively, and respective freedom from cardiac-related event rates were 96.5%, 90.3% and 63.5%. Conclusions CABG in patients with severe LV dysfunction provides optimal survival with an improved EF and functional state, and may provide a good alternative to transplantation in selected patients. (Circ J 2007; 71: 1862 - 1866)

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Background Cilostazol increases the cyclic adenosine monophosphate levels in platelets and might ameliorate the antiplatelet activity of clopidogrel. This study investigated the additional effect of cilostazol on platelet aggregation measured by a VerifyNow analyzer and soluble CD40 ligand (sCD40L) as a marker of activated platelet in patients undergoing primary percutaneous coronary intervention (PCI). Methods and Results Sixty cases of primary PCI were randomly assigned to dual (aspirin and clopidogrel) or triple (dual plus cilostazol) therapy. The antiplatelet effects of aspirin and clopidogrel were evaluated by VerifyNow tests. The plasma sCD40L levels at admission, 24 h and 21 days were measured by the ELISA method. The arachidonic acid induced platelet aggregation was similar in both groups. However, the triple group had a significantly lower P2Y₁₂ reaction unit (dual 208.8±69.0 vs triple 168.2±79.2, p=0.041) and higher % inhibition of adenosine diphosphate (ADP)-induced platelet aggregation (dual 23.8±21.4% vs triple 40.5±21.0%, p=0.004). In the multivariate analysis, cilostazol was a negative predictor for low responders to clopidogrel (95% confidence interval 0.067-0.711). The plasma sCD40L levels were not significantly different between the 2 groups at the same point of time. Conclusions The addition of cilostazol to the combination of aspirin plus clopidogrel significantly increases the inhibition of ADP-induced platelet aggregation. However, there was no additive effect on aspirin-induced antiplatelet activity or lowering of sCD40L. (Circ J 2007; 71: 1867 - 1872)

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Background No previous study has compared the transcardiac gradient of cardiac natriuretic peptides and prognosis. Methods and Results To compare the prognostic value of the transcardiac increase in brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in patients with chronic heart failure (CHF), the hemodynamic parameters and plasma levels of BNP and NT-proBNP were measured in the aortic root (AO) and coronary sinus (CS) in 353 consecutive patients with CHF. During a median follow-up of 2.8 years, 35 patients died. The molar ratio of (CS-AO) NT-proBNP to (CS-AO) BNP correlated with hemodynamic abnormalities and it was significantly higher in non-survivors than in survivors (median value =0.702 vs 0.437, respectively; p=0.0009), suggesting that NT-proBNP is superior to BNP in terms of transcardiac increase. After adjustment for clinical variables associated with CHF, including hemodynamics and an estimated glomerular filtration rate, it was found that only the plasma NT-proBNP level was an independent prognostic predictor, even after considering the transcardiac increases in BNP and NT-proBNP. Conclusion These findings suggest that the transcardiac gradient of NT-proBNP to BNP molar ratio increases with the severity of left ventricular dysfunction, and that plasma NT-proBNP level may be more useful than BNP for evaluating the prognosis of patients with CHF. (Circ J 2007; 71: 1873 - 1878)

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Background T cells in peripheral blood reflect the systemic inflammatory response in patients with heart failure (HF). In a rat model of HF, osteopontin is dramatically increased in the left ventricular myocardium, so the association between osteopontin and HF was examined in the present study. Methods and Results Peripheral blood was collected from 93 patients with heart disease and 38 controls. Left ventricular ejection fraction (LVEF) was calculated using a modified Simpson's rule. The 93 patients were classified into 3 classes according to the New York Heart Association (NYHA) functional classification. Osteopontin-expressing CD4⁺ T cells were quantified by flow cytometry. Plasma osteopontin levels (ng/ml) and the frequencies of osteopontin-expressing CD4⁺ T cells (%) were higher in patients with HF than in controls (800±554, 575±229, p=0.016 and 27.3±12.2, 16.7±10.0, p<0.001). Furthermore, the plasma osteopontin levels and the frequencies of osteopontin-expressing CD4⁺ T cells increased in proportion to the severity of the NYHA functional class. The frequencies of osteopontin-expressing CD4⁺ T cells were significantly correlated with LVEF (r=-0.336, p=0.0048) and log plasma brain natriuretic peptide levels (r=0.305, p=0.0025). Conclusions Osteopontin expression of circulating CD4⁺ T cells and plasma osteopontin levels reflect the severity of HF. Osteopontin could be a new target in the assessment of HF. (Circ J 2007; 71: 1879 - 1884)

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Background Cardiac resynchronization therapy (CRT) improves functional capacity in heart failure patients. This study aimed to prospectively analyze long-term device-based monitoring of physical activity in patients undergoing CRT. Methods and Results The Activity Log Index (ALI), calculated by CRT devices, represents the percentage of time when acceleration exceeds a threshold and monitors the physical activity. Data from 178 CRT patients (New York Heart Association III 91%, left ventricular ejection fraction 21±6%, left ventricular end-diastolic diameter 69±9 mm, QRS 159±27 ms, sinus rhythm 81%) were retrieved. The ALI increased from a baseline value of 3.6±2.0 to 11.2±4.6 (p<0.005) 104 weeks after initiation of CRT. A plateau was reached at approximately 12 weeks and thereafter ALI remained stable for up to 2 years. The magnitude of the changes in ALI was similar in patients with different etiologies and underlying rhythms. Despite similar values at baseline, elderly patients (≥65 years) exhibited significantly lower ALI values than younger patients during the follow-up and at the plateau (9.5±4.2 vs 13.3±4.8, p<0.001). Conclusions Device-based monitoring of physical activity in CRT patients is feasible. CRT resulted in a large and long-term increase in physical activity. (Circ J 2007; 71: 1885 - 1892)

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Background Myocardial remodeling is a crucial step for progression of heart failure (HF). Free radical generation by the failing myocardium has been proposed as linked to myocardial remodeling. The aim of this study was to evaluate the urinary excretion of 8-iso-prostaglandin F_2α (8-iso-PGF_2α), a reliable marker for oxidant stress in vivo, and collagen turnover in patients with acute worsening of congestive HF. Methods and Results Enrolled were 43 patients with acute worsening of congestive HF of various etiologies. On admission (acute phase) and after approximately 2 weeks of conventional treatment (chronic phase), the following were measured: (1) immunoreactive urinary 8-iso-PGF_2α, (2) serum total antioxidant status (TAS); and (3) serum levels of procollagen type I carboxyterminal peptide (PIP) and carboxyterminal collagen type I telopeptide (CITP), biochemical markers for collagen synthesis and degradation, respectively. From the acute to the chronic phase the parameters changed as follows: 335.1±245.4 to 205.3±107.4 pg/mg creatinine for urinary 8-iso-PGF_2α (p<0.0001); 0.92±0.16 to 0.98±0.13 mmol/L for TAS (p<0.01); 171.4±72.5 to 93.7±33.9 ng/ml for PIP (p<0.0001); and 7.2±3.6 to 12.6±8.4 ng/ml for CITP (p<0.0001). Conclusions Acute worsening of congestive HF promotes free radical generation and collagen synthesis. (Circ J 2007; 71: 1893 - 1897)

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Background The prognostic value of non-obstructive, CT low-dense plaques (CTLDP) on multislice computed tomography (MSCT) for the prediction of nonfatal acute myocardial infarction (AMI), unstable angina (UA) and cardiac death has not yet been defined. Methods and Results In the present study 810 patients who underwent MSCT and had non-obstructive coronary artery disease were followed up for the occurrence of AMI, UA and cardiac death. Non-obstructive CTLDP were defined as plaques with a CT density <68 Hounsfield units, accompanied by mild to moderate coronary artery stenosis (25-75%). Patients were followed-up for 1,062±544 days for the occurrence of (1) acute coronary syndrome (ACS) including nonfatal AMI and UA, and (2) cardiac death. CTLDP were detected in 189 patients (23.3%). The annual event rate of AMI, UA, ACS and cardiac death was 0.91%, 0.91%, 1.82% and 0.36%, respectively, in patients with CTLDP and 0.10%, 0.55%, 0.66% and 0.21%, respectively, in patients without CTLDP. The event rate of ACS was significantly higher in patients with CTLDP than in those without CTLDP (p<0.001). Multivariate Cox proportional regression analysis revealed that previous MI and the presence of CTLDP were independent predictors of ACS. Conclusion Non-obstructive CTLDP detected by MSCT yield prognostic information toward the identification of ACS. (Circ J 2007; 71: 1898 - 1903)

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Background Positive longitudinal pre-ejectional velocity (+PEV_L) was recently reported to be a reliable index of myocardial recovery early after successful revascularization in myocardial infarction (MI); that is, it recognizes the transmural extent of viable myocardium. The applicability of PEV_L in the real-world clinical setting for identifying the transmural extent of viable myocardium in reperfused recent MI was assessed. Methods and Results Using tissue Doppler imaging, the resting basal and mid myocardial PEV_Ls were determined within 3 days after revascularization in 41 consecutive patients with recent MI. Infarct thickness was semi-quantified using delayed gadolinium-enhanced magnetic resonance imaging (MRI) at baseline and at 6-month follow up to differentiate transmural from nontransmural MI. The proportion of segments showing the presence of +PEV_L was not significantly changed as infarct thickness increased (p=0.2), with 66.2% having +PEV_L even in segments involving >75% transmural infarction. Moreover, +PEV_L was found in a large fraction of segments with akinesia (70.4%). Specificity and negative predictive value of +PEV_L for assessing infarct nontransmurality were disappointingly low (32.0% and 26.9%, respectively). All of these results were not altered when the 6-month follow-up MRI was done. Conclusions +PEV_L cannot be regarded as a reliable marker for predicting the transmural extent of viable myocardium in recent MI. (Circ J 2007; 71: 1904 - 1911)

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Background Advances in transthoracic Doppler echocardiography enable noninvasive measurements of coronary flow velocity and coronary flow velocity reserve (CFVR) in the posterior descending coronary artery (PD). Methods and Results To evaluate CFVR in the PD of children with elevated right ventricular (RV) pressure, 19 children with RV pressure overload and 13 age-matched controls with normal RV pressure were studied using transthoracic Doppler echocardiography. Average peak flow velocity (APV) was measured at rest and in hyperemic conditions (intravenous administration of adenosine of 0.16 mg · kg^-1 · min^-1). Compared with controls, the PD CFVR was significantly reduced in the patients with elevated RV pressure (1.87±0.42 vs 2.49±0.55, p<0.01) because their mean baseline APV was significantly greater (27±6 vs 19±4 cm/s, p<0.01), although hyperemic APV was not significantly different (49±10 vs 48±14 cm/s, p=NS). Conclusions PD CFVR is limited in patients with elevated RV pressure because of elevation of the baseline resting flow velocity. (Circ J 2007; 71: 1912 - 1917)

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Background Catheter ablation inside the Koch's triangle has a risk for complete atrioventricular block. Methods and Results The anatomic size of the coronary sinus (CS) and His bundle (HB) in children and the distance between them was studied using a 3-dimensional electroanatomical mapping system (CARTO). Fifty-three children (mean age, 11.8±3.7 years) without congenital heart disease (ie, 24 with atrioventricular re-entrant tachycardia, 18 with atrioventricular nodal re-entrant tachycardia, 7 with atrial tachycardia, 2 with ventricular tachycardia and 2 with atrial flutter) were studied. The size of the HB recording area was 148±97 mm² and the size of the CS was 66±44 mm². The size of the CS and the distance between the HB and CS (18±7 mm) were proportional to body weight, body length and body surface area. All patients underwent catheter ablation, including 25 ablations inside Koch's triangle. Catheter ablation was successful in 52 patients without any atrioventricular nodal injury. Conclusions The CS size and the distance between the HB and CS increased proportionally with children's growth. To know the distance from the HB to the ablation point is useful in avoiding atrioventricular node injury, and information about the length of Koch's triangle may provide supportive information when applying radiofrequency energy inside Koch's triangle without needing to use the CARTO system in children, but this merits further investigation. (Circ J 2007; 71: 1918 - 1921)

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Background Achievement of complete conduction block in the cavotricuspid isthmus (CTI) is a curative ablation technique in patients with common atrial flutter (AFL). The present study was a prospective comparison of the efficacy of 2 ablation strategies in patients with common AFL: the continuous and point-by-point radiofrequency (RF) delivery techniques. Methods and Results Forty patients with common AFL were randomly assigned to either a group treated with a continuous RF delivery or to a group undergoing point-by-point RF ablation. In the first group, the RF energy was continuously delivered during a slow drag of the catheter tip from the tricuspid annulus to the inferior vena cava without stopping the application. In the second group, the RF ablation was performed using a point-by-point approach for 60 s at each point. All patients underwent ablation with an 8-mm-tip ablation catheter with a power limit of 50 W and a target temperature of 55°C. Complete CTI conduction block was achieved in all patients. The patient characteristics, including the anatomy of the CTI estimated by 3-dimensional computed tomography, were no different between the 2 groups. The procedure time (time from the start of RF delivery to the completion of CTI block), fluoroscopic time and total RF energy required to create the CTI block between the continuous and point-by-point groups were 7.3±5.6 vs 21.2±22.2 min (p<0.01), 7.2±4.4 vs 16.2±14.1 min (p<0.05), and 15,631±6,001 vs 24,072±16,140 joules (p<0.05), respectively. There were no complications or recurrences of AFL during the follow-up period in any of the patients. Conclusion In the curative treatment of common AFL, the continuous RF delivery approach could shorten the procedure and fluoroscopic time and reduce the total RF energy compared with the point-by-point RF ablation approach. (Circ J 2007; 71: 1922 - 1926)

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Background Impaired renal function is associated with poor outcomes among patients with chronic heart failure (CHF). However, the long-term changes in renal function in CHF patients without renal insufficiency at initial diagnosis remain unclear. Methods and Results Retrospective analysis of patients presenting with idiopathic dilated cardiomyopathy (IDCM) from 1984 to 2003 and who had normal renal function defined as estimated creatinine clearance (eCcr) ≥60 ml/min at the first diagnosis. Cumulative event proportions and renal insufficiency defined as eCcr <60 ml/min were calculated by the Kaplan-Meier method. The predictors of renal insufficiency were evaluated by logistic regression analysis. Impaired renal function developed in 20% during an 8-year follow-up and in 50% during a 20-year follow-up. Advanced age at the first diagnosis, high frequency of admissions, and hypotension during the clinical course were associated with the occurrence of impaired renal function. Beta-blocker therapy was a negative predictor of renal insufficiency. Conclusions In patients with IDCM without renal insufficiency at initial diagnosis, worsening renal function occurred during the follow-up period. Frequent admissions, hypotension, and lacking β-blocker therapy were associated with a poor prognosis in renal function. (Circ J 2007; 71: 1927 - 1931)

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Background It was recently suggested that the angiotensin-converting enzyme insertion/insertion genotype, which is considered to be protective against cardiovascular disease, was a significant risk factor for atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to investigate the association between the endothelin-2 (EDN2) A985G polymorphism and AF in patients with HCM. Methods and Results The EDN2 A985G polymorphism (rs 5800) was genotyped in 110 patients with HCM who had no clinically documented AF before medical treatment. The distribution of the EDN2 genotypes (G/G, G/A, and A/A) was 77.3%, 19.1%, and 3.6%, respectively. The EDN2 A allele frequency was 0.21 in 26 patients who subsequently developed AF during long-term follow-up and 0.11 in 84 patients who remained in sinus rhythm. The distribution of genotypes of the dominant EDN2 A allele between the two groups was significantly different by chi-square analysis (42.3% vs 16.7%, p=0.014). In a multivariate model, the A985 allele of the EDN2 gene was associated with increased adjusted risk for the occurrence of AF (p=0.018). Conclusion The EDN2 A985 allele, which is considered to be protective in cardiovascular disease, may be a risk factor for AF in patients with HCM. (Circ J 2007; 71: 1932 - 1936)

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Background Cardiac sarcoidosis is frequently overlooked or misdiagnosed as idiopathic dilated cardiomyopathy (DCM), primarily because of difficulties in its diagnosis. This is a crucial issue because appropriate therapy with immunosuppressive agents can be initiated if early diagnosis is achieved. Methods and Results Thoracic computed tomography (CT) was retrospectively analyzed in detail with special reference to lymph node swelling (LNS) in the mediastinum of 8 patients diagnosed with idiopathic DCM who underwent left ventriculoplasty (LVP), and were later proven to have active cardiac sarcoidosis by histological evaluation of the resected myocardium. Twenty age-matched patients with idiopathic DCM who also underwent LVP served as controls. On conventional chest radiographs, none of the cardiac sarcoidosis patients exhibited lymph node involvement, including bilateral hilar lymphadenopathy. However, CT demonstrated significant mediastinal LNS in 7 (88%) of them and in only 1 (5%) of the 20 controls. There was a significant difference in the incidence of LNS in the 2 groups (p=0.00005). Conclusion Evaluation of mediastinal lymphadenopathy by CT is an easy and valuable initial screening method for distinguishing cardiac sarcoidosis from idiopathic DCM. (Circ J 2007; 71: 1937 - 1941)

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Background The prevalence and indicative clinical factors of renal artery stenosis (RAS) in the Japanese population are unclear. Methods and Results The aim of this study was to investigate the prevalence of RAS in a selectively referred Japanese population and to determine any clinical factors related to RAS by initially screening with renal duplex ultrasonography. The 750 patients presenting because of possible or known cardio-and cerebrovascular diseases were prospectively studied. Duplex examination was performed in 729 patients (97.2%): 21 patients (2.8%) did not undergo it, because of technical impossibility. Duplex RAS was found in 38 patients (5.2%). Subsequently, a confirmatory renal angiography was obtained in 40 patients, investigating those who had duplex RAS or no duplex examination. Angiographic RAS was found in 35 patients (4.8%). The respective prevalences of duplex and angiographic RAS were 6.3% and 6.7% in coronary artery disease, 8.8% and 9.3% in multivessel coronary artery disease, 7.5% and 8.2% in heart failure, 5.1% and 4.3% in unstable angina pectoris, 20.0% and 22.2% in carotid artery stenosis, 10.3% and 10.2% in stroke, 20.0% and 20.0% in peripheral artery disease, and 12.0% and 11.8% in abdominal aortic aneurysm. Univariate analysis showed that patients with duplex RAS were older and had more atherosclerotic risk factors. Furthermore, they were more likely to be smokers and have hypertension, renal impairment, renal atrophy, left ventricular hypertrophy and cardio- and cerebrovascular diseases. Multivariate stepwise analysis showed that smoking, peripheral artery disease, abdominal aortic aneurysm and renal atrophy were independent predictors of duplex RAS. Conclusions RAS is frequent in Japanese patients with cardio- and cerebrovascular diseases. Initial screening for RAS by duplex ultrasonography is recommended for patients with complications, especially peripheral artery disease, abdominal aortic aneurysm and renal atrophy. (Circ J 2007; 71: 1942 - 1947)

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Background The purpose of this study was to evaluate the usefulness and safety of multidetector-row computed tomography (MDCT) pulmonary angiography and indirect venography management of acute pulmonary embolism (PE), including indication for inferior vena cava (IVC) filter. Methods and Results Seventy-one consecutive patients who were clinically suspected of PE and underwent 16-slice MDCT pulmonary angiography and indirect venography were enrolled. Management included indication of IVC filter for patients with extensive deep venous thrombosis (DVT) in submassive or massive PE. A right ventricular to left ventricular short-axis diameter by MDCT >1.0 was judged as submassive PE. All patients were followed for 1 year. MDCT identified 50 patients with venous thromboembolism and 47 patients had acute PE: 4 were judged as massive, 14 as submassive, and 29 as non-massive by MDCT; 3 patients had DVT alone and 7 patients had caval or iliac DVT. Only 1 patient with massive PE and DVT near the right atrium died of recurrence. No other patients died of PE. Conclusion Management based on MDCT pulmonary angiography combined with indirect venography is considered to be safe and reliable in patients with suspected acute PE. (Circ J 2007; 71: 1948 - 1954)

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Background Increased cardiac insulin-like growth factor (IGF)-I production is associated with physiological cardiac hypertrophy in athletes, and IGF-I has been recognized as a cardioprotective agent in experimental animal studies. On the other hand, acromegaly which is characterized by an excess of IGF-I has been linked to impaired cardiac function. Methods and Results Both the relationship between the serum levels of IGF-I and brain natriuretic peptide (BNP), which is released from the cardiac ventricles in response to ventricular stress, and that between IGF-I and the concentrations of the plasma amino-terminal propeptide of procollagen type III (P-III-P), which is associated with myocardial fibrosis, were evaluated in 19 patients after surgical treatment for acromegaly. Echocardiography revealed that left ventricular systolic function and dimensions were within normal range in all patients. Significant inverse correlations were found between IGF-I and the BNP (r=-0.5, p=0.02) and P-III-P levels (r=-0.62, p=0.005). Conclusion We observed an inverse significant relationship between IGF-I and both the BNP and P-III-P value in surgically treated acromegaly patients. These observations suggest that appropriate levels of IGF-I have beneficial cardioprotective effects after surgery in patients with acromegaly. (Circ J 2007; 71: 1955 - 1957)

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Background Angiotensin II (AT) is implicated in the development of cardiac remodeling, which leads to heart failure, and pharmacological inhibition of the AT type 1 (AT₁) receptor has improved mortality and morbidity in patients of heart failure. The aim of this study was to elucidate the role of the AT₁ receptor in disease progression in muscle LIM protein (MLP)-deficient mice, which are susceptible to heart failure because of defective function of mechanosensors in cardiomyocytes. Method and Results Hearts from MLP knockout (MLPKO) mice and MLP-AT_1a receptor double knockout (DKO) mice were analyzed. MLPKO hearts showed marked chamber dilatation with cardiac fibrosis and reactivation of the fetal gene program. All of these changes were significantly milder in the DKO hearts. Impaired left ventricular (LV) contractility and filling were alleviated in DKO hearts. However, the impaired relaxation and downregulated expression of sarcoplasmic reticulum calcium-ATPase 2 were unchanged in DKO hearts. Conclusions The AT_1a receptor is involved in progression of LV remodeling and deterioration of cardiac function in the hearts of MLPKO mice. These results suggest that blockade of the receptor is effective in preventing progression of heart failure in dilated cardiomyopathy. (Circ J 2007; 71: 1958 - 1964)

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Background Sildenafil citrate (Viagra) is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5, which might enhance the vasorelaxant and natriuretic actions of atrial natriuretic peptide (ANP) in patients with heart failure. The objective of this study was to examine the combined effect of Viagra on hemodynamic changes during infusion of exogenous ANP. Methods and Results Healthy male beagles were used to assess systemic blood pressure, pulmonary artery pressure (PAP), and plasma levels of cGMP. After hemodynamic variables were measured, 0.1 μg · kg^-1 ·min^-1 of ANP was given during this study. One hour after initiating infusion of ANP, 2 mg/kg of sildenafil citrate or vehicle was given orally via a nasogastric tube. Hemodynamic changes were measured before and 1 h after these administrations. Mean systemic and PAP decreased during infusion of ANP, and further decreased after sildenafil citrate administration, however, mean systemic blood pressure decreased within 10 mmHg. Plasma levels of cGMP also increased after sildenafil citrate administration. Conclusion In normal dogs, sildenafil citrate enhances the vasodilator effect of ANP by increasing the cGMP level, however, the concomitant use of sildenafil citrate with ANP will not induce severe hypotension. (Circ J 2007; 71: 1965 - 1969)

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Background The T-type Ca²⁺ channel (TCC) is activated, and abnormalities of the TCC may be related to the pathogenesis of Ca²⁺ overload, in cardiomyopathic hamster hearts. The aims of the present study were to investigate the alteration in expression of the TCC and to examine the effects of a dual L-and T-type Ca²⁺ channel blocker, efonidipine (EFO), on cardiac function and TCC during development of heart failure in UM-X7.1 cardiomyopathic hamsters. Methods and Results UM-X7.1 and golden hamsters were examined, and EFO was administered at the age of 20 weeks for 4 weeks. Cardiac function was examined, the expression of TCCα1G was measured, and ventricular myocytes were subjected to a patch-clamp study. At 24 weeks, vehicle-treated UM-X7.1 hamsters exhibited significant increases in left ventricular (LV) size, with marked decreases in ejection fraction (LVEF) compared with golden hamsters. In the UM-X7.1 group, the expression of TCCα1G increased during development of heart failure compared with the golden hamster group. In the UM-X7.1 group, EFO treatment significantly attenuated the decrease of LVEF without affecting blood pressure compared with the vehicle group. EFO treatment decreased heart rate (by~10%) in both groups. In the golden hamster group, EFO treatment did not affect LV function. The TCC current in ventricular myocytes was significantly increased in UM-X7.1, and was inhibited by EFO in a dose-dependent manner. Conclusions In cardiomyopathic hamster hearts, abnormalities in the TCC may be at least in part related to the pathogenesis of abnormal Ca²⁺ homeostasis, and TCC-blocker treatment may decrease the TCC current, resulting in an improvement of cardiac function. TCC blocker therapy might be a new strategy for certain types of heart failure. (Circ J 2007; 71: 1970 - 1976)

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Background The reverse-remodeling effect of angiotensin II type 1 receptor blocker (ARB) on atrial fibrillation (AF) is unclear. Methods and Results Sustained AF was induced in 20 dogs by 4-week rapid atrial pacing. The AF duration, atrial effective refractory period (AERP) and intra-atrial conduction time (CT) were measured every 2 weeks. After 4-week pacing, dogs were randomly assigned to control (n=10) and ARB (olmesartan; n=10) groups. Olmesartan was administered orally (3 mg · kg^-1 · day^-1) after pacing was terminated, and continued for the 4-week recovery period. After 4-week pacing, AERP shortening, CT prolongation and AF maintenance were not significantly different between the 2 groups. During the recovery, AERP recovered to baseline in both groups. CT remained prolonged in the control group during the recovery, but recovered to baseline in the olmesartan group. The mean AF duration in the olmesartan group after 4-week-recovery was significantly shorter than that in the control group (58±20 vs 1,337±226 s, p<0.001). Olmesartan significantly decreased interstitial fibrosis compared with the control group (9±1% vs 15±1 at the right atrial appendage, p<0.001). Conclusion Olmesartan has a reverse-remodeling effect on AF-induced structural changes, indicating that it may be useful for preventing AF recurrence after the termination of sustained AF. (Circ J 2007; 71: 1977 - 1982)

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A patient underwent radiofrequency (RF) catheter ablation for a drug-refractory ventricular tachycardia, but RF energy application at an endocardial site of the left ventricular outflow tract and at the left sinus of Valsalva could not eliminate the tachycardia. The earliest ventricular activation during the arrhythmia, which preceded the onset of the QRS complex by 32 ms, was found within the great cardiac vein and complete elimination of the tachycardia was finally achieved with RF application at that site. (Circ J 2007; 71: 1983 - 1988)

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Two cases of paroxysmal atrial fibrillation (AF) first occurred 15 and 36 years, respectively, after isolated direct suture closure of an atrial septal defect (ASD) and failed to be controlled by antiarrhythmic drug therapy. In these cases, an atrial transseptal procedure was feasible and no residual iatrogenic ASD was observed, even after multiple procedures. Pulmonary vein (PV) isolation was also feasible and safe and could eliminate the AF completely. PV isolation may become an alternative to antiarrhythmic drug therapy in patients with paroxysmal AF occurring late after an isolated direct suture closure of an ASD. (Circ J 2007; 71: 1989 - 1992)

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A case of catecholamine cardiomyopathy associated with paraganglioma, which was rescued by percutaneous cardiopulmonary support system (PCPS), is presented. Unlike typical apical ballooning, transthoracic echocardiography and left ventriculography revealed severe left ventricular (LV) dysfunction and an abnormal contractile pattern, consisting of akinesis of the basal and midventricular segments and hyperkinesis of the apical segments. Because of the intractable cardiogenic shock, despite conventional treatment, PCPS was performed. The underlying disease was paraganglioma. Catecholamine excess may induce not only transient LV apical ballooning but also atypical LV ballooning without involvement of the LV apex. Early use of PCPS is important for the patient with a catecholamine crisis who is not stabilized by intra-aortic balloon pump as well as infusion of fluid and inotropic agents. (Circ J 2007; 71: 1993 - 1995)

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Aneurysmal circumflex coronary artery (Cx) with fistulous connection to the coronary sinus is a rare clinical entity that usually remains asymptomatic until later in life, so the ideal therapeutic strategy is poorly defined. The timing of surgical treatment for asymptomatic patients is a big issue, and whether to leave or exclude the diffuse aneurysm in addition to ligation of the fistula is controversial, considering the native myocardial circulation. Complete surgical repair, including exclusion of a diffusely aneurysmal Cx and coronary revascularization to a graftable branch in the circumflex area combined with ligation of its fistula, is quite challenging and sometimes fatal because of a broad posterolateral myocardial infarction without revascularization caused by a lack of graftable branches. A case of diffuse aneurysmal Cx, which ruptured into the left atrium after surgical ligation of its fistulous connection to the coronary sinus, is presented. Simple ligation of the fistula, leaving a gigantic aneurysmal circumflex artery, is hazardous for later rupture and should be avoided. Therapeutic strategies for this complex disorder are discussed, including the optimal timing of surgical treatment. (Circ J 2007; 71: 1996 - 1998)

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