Despite recent advances in the understanding and etiology of cardiovascular disease, it remains the leading cause of morbidity and mortality worldwide. A great deal of research has been dedicated to investigating and identifying plaque instability: the so-called "vulnerable plaque". A reliable, in vivo, imaging method capable of identifying plaque characteristics associated with high-risk plaque will be immensely useful for evaluating plaque status and predicting future events. With excellent soft-tissue contrast and resolution, magnetic resonance imaging (MRI) has the ability to visualize features of vulnerable plaques, as well as perform longitudinal studies on the etiology, progression, and regression of atherosclerotic plaque. This review will cover the current state-of-the-art and new developments in carotid MRI to characterize atherosclerosis and its use in clinical diagnoses and longitudinal studies to understand mechanisms of lesion progression and regression. (Circ J 2009; 73: 1765-1773)

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Sex differences in morbidity and mortality associated with cardiovascular disease have been recognized by the medical community for decades. Investigation into the underlying biological basis of these differences was largely neglected by the scientific community until a report released by the Institute of Medicine in the United States in 2001 "Exploring the Biological Contributions to Human Health: Does Sex Matter?" Recommendations from this report included the need for more accurate use of the terms "sex" and "gender", better tools and resources to study the biological basis of sex differences, integration of findings from different levels of biological organization and continued synergy between basic and clinical researchers. Ten years after the Institute's report, this review evaluates some of the sex differences in cardiovascular disease, reviews new approaches to study sex differences and emphasizes areas where further research is required. In the era of personalized medicine, the study of the biological basis of sex differences promises to optimize preventive, diagnostic and therapeutic strategies for cardiovascular disease in men and women, but will require diligence by the scientific and medical communities to remember that sex does matter. (Circ J 2009; 73: 1774-1782)

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The discovery of endothelial-derived relaxing factor, and later nitric oxide (NO), as a biologically active substance led to intense focus on the vascular endothelium as a major site of physiological regulation and pathophysiological dysfunction. NO is clearly a potent vasodilator and plays a key role in establishing both whole body and regional "vascular tone". In this context, skeletal muscle and human skin have the remarkable capacity to increase their blood flow 50-100-fold and this increase is caused almost exclusively by local vasodilation. In general, the mechanisms responsible for these vasodilator phenomena have been poorly understood. In the early 1990s, investigators started to ask if NO might explain the "unexplained" vasodilator responses seen in skeletal muscle and skin. They also asked how "NO tone" interacted with "sympathetic tone" and whether NO can override the vasoconstrictor responses normally generated when sympathetic nerves release norepinephrine. Surprisingly, it was found that NO plays only a modest (non-obligatory) role in exercise hyperemia, reactive hyperemia and the neurally mediated rise in skin blood flow during whole body heat stress. By contrast, NO plays a major role in the skeletal muscle vasodilator responses to mental stress and the skin dilator responses to local heating. In animals, but not humans, NO can limit the ability of the sympathetic nerves to cause vasoconstriction in exercising muscles. Thus the role of NO in two of the most extreme dilator responses seen in nature is limited and in muscle the sympathetic nerves can restrain the dilation to defend arterial blood pressure. (Circ J 2009; 73: 1783-1792)

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Background: Ventricular fibrillation (VF) during prolonged (>5 min) global ischemia (GI) could be due to repetitive endocardial focal discharges (REFDs). This hypothesis was tested in isolated rabbit hearts. Methods and Results: With optical mapping, simultaneous endocardial (left ventricle, LV) and epicardial (both ventricles) activations during VF with prolonged GI were studied (protocol I, 8 hearts). Lugol solution was applied to the LV endocardium in additional 5 hearts after 5-min GI (protocol II). During prolonged GI, sustained VF (>30 s) was successfully induced in 7 protocol I hearts. The dominant frequency of summed optical signals at the LV endocardium was higher than at the epicardium (P<0.05). Mapping data showed that after 5-min GI, REFDs were present in >90% for recording time. There were 18 windows of optical recording showing spontaneous VF termination. In 10, once REFDs ceased, the VF episode terminated immediately. Electrical defibrillation was also performed on 3 hearts. Eight shocks showed early VF recurrence after successful defibrillation. REFDs were consistently involved in the initiation period of recurrence. In protocol II, Lugol subendocardial ablation diminished REFD genesis during re-induced VF. These VF episodes were all non-sustained. Conclusions: REFDs at the LV endocardium were important for both VF maintenance and post-shock recurrence during prolonged GI in this model. (Circ J 2009; 73: 1803-1811)

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Background: Optimal right ventricular (RV) pacing site in patients referred for permanent cardiac pacing remains controversial. A prospective randomized trial was done to compare long-term effect of permanent RV apex (RVA) vs RV outflow tract (RVOT) pacing on the all-cause and cardiovascular mortality. Methods and Results: A total of 122 consecutive patients (70 men, 69 ±11 years), with standard pacing indications were randomized to RVA (66 patients) or RVOT (56 patients) ventricular lead placement. After the 10-year follow-up period the mortality data were summarized on the basis of an intention-to-treat analysis. During the long-term follow-up, 31 patients from the RVA group died vs 24 patients in the RVOT group (hazard ratio (HR), 0.96; 95% confidence interval (CI), 0.57-1.65; P=0.89). There were 10 cardiovascular deaths in the RVA and 12 in the RVOT group (HR, 1.04; 95%CI, 0.45-2.41; P=0.93). There were no differences in the all-cause or cardiovascular mortality between the pacing sites after adjustment for age, gender, arterial hypertension, atrial fibrillation, New York Heart Association class and left ventricular end-diastolic diameter. Conclusions: The RVOT provides no additional benefit in terms of long-term survival over RVA pacing. (Circ J 2009; 73: 1812-1819)

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Background: This study evaluated antiarrhythmic effects of d,l-sotalol in a canine atrial fibrillation (AF) model with left ventricular dysfunction. Methods and Results: Thirteen beagles (Sotalol group n=7 and Control group n=6) were subjected to atrial tachypacing (ATP) (400 beats/min) with intact atrioventricular conduction for 4 weeks. Oral d,l-sotalol (2 mg/kg) was administered 1 week after starting ATP and continued throughout the experiment. One week after starting ATP, atrial effective refractory periods (AERPs) were shortened in both groups. However, d,l-sotalol treatment gradually prolonged AERP, resulting in a significant prolongation of AERP compared with the Control group at 4 weeks (Control 76 ±4 and Sotalol 126 ±5 ms, p<0.01). d,l-Sotalol treatment showed lower AF inducibility and shorter AF duration at 4 weeks. In the control group, expressions of L-type Ca²⁺ channel α1c and Kv4.3 mRNA were downregulated by 46.2% and 43.0%, respectively, after 4 weeks of ATP; d,l-sotalol treatment did not affect these changes. Conclusions: d,l-Sotalol treatment prolonged AERP, even after atrial electrical remodeling had developed, and prevented AF perpetuation without affecting downregulated expression of L-type Ca²⁺ channel α1c and Kv4.3 mRNA in an ATP-induced canine AF model. (Circ J 2009; 73: 1820-1828)

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Background: Right ventricular septal (RVS) pacing is an alternative to right ventricular apical (RVA) pacing, but there is limited information about its influence on long-term left ventricular (LV) synchrony and function. Methods and Results: A total of 55 patients undergoing dual-chamber pacemaker implantation with normal QRS duration and preserved LV function at baseline were included in the study. The right ventricular lead was implanted on the septum where it would produce the shortest QRS duration possible in 40 patients and in the apex in 15. The time-to-peak systolic velocity (T_sys) was measured in 12 segments of the LV wall by tissue Doppler imaging. After a long (~4 years) follow-up period, the LV ejection fraction (LVEF) decreased significantly in patients with RVA pacing but not in those with RVS pacing. Paced QRS duration was significantly shorter during RVS than RVA pacing. T_sys dispersion among the 12 LV segments was significantly smaller during RVS than RVA pacing. There was a positive correlation between the paced QRS duration and T_sys dispersion (R=0.65, P<0.0001). The pacing-induced decrease in LVEF was positively correlated with the degree of T_sys dispersion (R=0.42, P=0.008). Conclusions: RVS pacing guided by the paced QRS morphology preserves long-term LV function via minimizing LV dyssynchrony. (Circ J 2009; 73: 1829-1835)

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Background: A drug provocation test is performed to unmask a type 1 electrocardiogram (ECG) in individuals with saddle-back type ST-segment elevation in the right precordial leads (SB-ECG). The study investigated predictors of positive responders (PR) by drug testing. Methods and Results: A total of 58 consecutive individuals with SB-ECG in lead V2 were enrolled and drug testing was performed. In leads V2 at standard and the third intercostal space (V2_IC3), the QRS duration was measured, the amplitudes of r' wave (r'), ST-segment 20 and 40 ms after the r' wave (r'20 and r'40, respectively), the bottom of the ST-segment (ST_b), the differences between r' and r'20 (r'-r'20), r' and r'40 (r'-r'40), r' and ST_b (r'-ST_b), and the descending rate of the ST-segment [(r'-r'20)/r'; DR20, (r'-r'20)/(r'-ST_b); DR20-ST_b] were also measured. Thirty-five PR had significantly longer QRS duration, larger r'20 and r'40, and smaller r'-r'20, DR20, and DR20-ST_b than negative responders. DR20 and DR20-ST_b in leads V2 and V2_IC3 were most significantly different between 2 groups. The positive and negative predictive values of `DR20-ST_b in lead V2_IC3 <0.62' for prediction of positive tests were 92.3% and 81.8%, respectively. Conclusions: In individuals with SB-ECG, DR20 and DR20-ST_b in leads V2 and V2_IC3 might be useful predictors of positive testing. (Circ J 2009; 73: 1836-1840)

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Background: Factors influencing measurements and accurate evaluation of stent apposition by optical coherence tomography (OCT) are not established. Methods and Results: Phantom models of known luminal sizes and lengths were evaluated by OCT under various conditions and measurements were compared with actual values. Stents implanted into phantom models were examined by OCT to validate the measurement point on the stent strut surface for accurate evaluation of stent apposition. Strut thickness was measured at 3 points (midpoint, inner and outer surfaces of the stent shadow). The precision of OCT measurements of lumen diameter and area was satisfactory when the image wire was positioned in the center, but the error and deviation were unsatisfactory when the image wire was positioned eccentrically using a low frame acquisition rate. Longitudinal OCT measurements were close to actual values under all conditions examined. Measurements from the midpoint of the stent shadow to the adjacent vessel wall surface coincided with actual stent thickness. Conclusions: Significant measurement error can occur if the image wire is positioned eccentrically with a lower frame acquisition rate than specified by the manufacturer. To accurately evaluate stent apposition, the stent surface should be measured from the center of the stent reflection. (Circ J 2009; 73: 1841-1847)

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Background: The aim of the present study was to compare the effects of drug-eluting stents (DES) and coronary artery bypass grafting (CABG) in patients suffering from chronic stable angina with multivessel disease, involving significant proximal stenosis in the left anterior descending artery (LAD). Methods and Results: All consecutive patients suffering from chronic stable angina with multivessel disease involving significant proximal LAD stenosis underwent DES implantation (n=600) or CABG (n=709) at our institution. At 2 years, the unadjusted mortality was significantly lower in the DES group than in the CABG group (2.2% vs 5.2%, P=0.004), but the adjusted risk of death was similar (odds ratio (OR) 0.74, 95%CI 0.28-1.97, P=0.555). Furthermore, both the adjusted rate of nonfatal myocardial infarction and cerebrovascular events was also comparable. However, the unadjusted and adjusted risk of major adverse cardiac cerebrovascular events in the DES was significantly higher than in the CABG (13.3% vs 9.6%, OR 2.71, 95%CI 1.56-4.74, P<0.001), which is probably attributed to the higher subsequent revascularization rate after DES implantation. Conclusions: DES showed comparable long-term mortality for the treatment of multivessel disease involving significant proximal stenosis in LAD in comparison with CABG. (Circ J 2009; 73: 1848-1855)

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Background: Sirolimus-eluting stent (SES) has revolutionized interventional cardiology. Its application is spreading to complex, high-risk subsets of patients and lesions. Therefore, it is important to determine the factors associated with post-SES restenosis. Methods and Results: The study investigated 341 patients with angina pectoris, in whom SES was implanted. The coronary artery calcification (CAC) degree was assessed using the angiographic scoring system as follows: 0, none; 1, blocky or spotty calcification; 2, linear calcification compromising 1 side of the arterial lumen; 3, linear calcification found unidirectionally compromising both sides of the arterial lumen; 4, linear calcification found bidirectionally compromising both sides of the arterial lumen; and 5, blanket/circumferential and dense calcification. Restenosis was observed in 23 patients (7.3%). The target lesion (1.8 ±1.7 vs 0.7 ±1.1 [mean ± SD]) and stent delivery route CAC scores (3.1 ±2.5 vs 1.4 ±2.0) were significantly higher in patients with restenosis than in those without it (P<0.0001). In multivariate analysis, the CAC score of the stent delivery route was independently associated with restenosis (odds ratio of 6.804, P<0.05), although CAC score of the target lesion was not. Conclusions: CAC in the stent delivery route is an important determinant of post-SES restenosis. (Circ J 2009; 73: 1856-1863)

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Background: The aim of the current study was to determine if the slowed exercise oxygen uptake (VO₂) kinetics, which is developed by myocardial ischemia, would be accompanied by delayed recovery VO₂ kinetics in patients with coronary artery disease (CAD). Methods and Results: Thirty-seven patients with significant ST depression during treadmill exercise underwent cardiopulmonary exercise testing with cycle ergometer. Measurements performed are the ratios of change in increase in oxygen (O₂) uptake relative to increase in work rate (ΔVO₂/ΔWR) across anaerobic threshold (AT) and 1 mm ST depression point (ST-dep), the time constants of VO₂ during recovery (T_1/2 VO₂), stress radio-isotope scintigraphy and coronary angiography. Patients were divided into CAD positive (CAD+) and CAD negative (CAD-) groups, based on coronary angiography. In CAD+, ΔVO₂/ΔWR decreased above AT and ST-dep, in contrast to CAD- patients. The T_1/2 VO₂ in CAD+ (103.1 ±13.0 s) was greater than that of CAD- (76.5 ±8.7 s) and showed negative correlations to the ratios of ΔVO₂/ΔWR across AT and ST-dep. These parameters improved in the patients who underwent coronary bypass surgery. Conclusions: Exercise and recovery VO₂ kinetics were slowed when myocardial ischemia was provoked by exercise. Measurement of exercise and recovery VO₂ kinetics improve the accuracy of the exercise electrocardiogram diagnosis of CAD. (Circ J 2009; 73: 1864-1870)

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Background: The Borg Scale may be a useful tool for heart failure patients to self-monitor and self-regulate exercise on land or in water (hydrotherapy) by maintaining the heart rate (HR) between the anaerobic threshold and respiratory compensation point. Methods and Results: Patients performed a cardiopulmonary exercise test to determine their anaerobic threshold/respiratory compensation points. The percentage of the mean HR during the exercise session in relation to the anaerobic threshold HR (%EHR-AT), in relation to the respiratory compensation point (%EHR-RCP), in relation to the peak HR by the exercise test (%EHR-Peak) and in relation to the maximum predicted HR (%EHR-Predicted) was calculated. Next, patients were randomized into the land or water exercise group. One blinded investigator instructed the patients in each group to exercise at a level between "relatively easy and slightly tiring". The mean HR throughout the 30-min exercise session was recorded. The %EHR-AT and %EHR-Predicted did not differ between the land and water exercisegroups, but they differed in the %EHR-RCP (95 ±7 to 86 ±7, P<0.001) and in the %EHR-Peak (85 ±8 to 78 ±9, P=0.007). Conclusions: Exercise guided by the Borg scale maintains the patient's HR between the anaerobic threshold and respiratory compensation point (ie, in the exercise training zone). (Circ J 2009; 73: 1871-1876)

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Background: Several investigators have emphasized the positive effect of hypothermia therapy on patients who have suffered from cardiac arrest. Salvaging patients from circulatory collapse is a pivotal task, but it is unclear whether additional hypothermia can practically contribute to an improvement in the neurological outcome. Methods and Results: Since December 2005, our hospital has been using hypothermia therapy. Forty-six comatose patients after recovery of spontaneous circulation were consecutively enrolled in the present study. Twenty-five of the enrolled patients received hypothermia therapy and 21 did not because they were treated prior to 2005. The time from collapse to spontaneous circulation (P=0.09), the rates of performance of bystander CPR (P=0.370) and presence of a witnessed collapse (P=0.067) were not significantly different between the recovery group (n=28) and the non-recovery group (n=18). The additional hypothermia therapy was an independent predictor of neurological recovery (P=0.005, OR 6.5, 95%CI 1.74-24.27). The recovery rate was significantly higher in patients who received hypothermia therapy (80%) compared to those who did not (38%). Conclusions: Hypothermia therapy is very useful for treating patients who have had an out-of-hospital cardiac arrest; it should be induced rapidly and smoothly. (Circ J 2009; 73: 1877-1880)

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Background: The purpose of this study was to determine the discriminate gender-specific cutoff values of waist circumference (WC) for detecting the clustering of cardiovascular risk factors (CCRF), which reflects the intra-abdominal visceral fat area (VFA) using a large Japanese population. Methods and Results: The study population consisted of 6,736 men and women who underwent a periodic health check-up and had a computed tomography scan for VFA measurement at the PL Tokyo Health Care Center in Tokyo, Japan. The CCRF was defined according to the Japanese Committee of the Criteria for Metabolic Syndrome. The discriminate values for detecting the CCRF were tested using receiver operating characteristics analysis. The discriminate values of VFA were 103.0 cm² with 68.7% sensitivity and 61.8% specificity for men and 69.0 cm² with 80.8% sensitivity and 70.0% specificity for women. The WC values corresponding to the VFA were 89.1 cm for men and 86.3 cm for women. The discriminate values of VFA and WC were not substantially different between people with or without raised blood pressure. Conclusions: For the early detection and management of the CCRF and VFA in the primary screening setting, the discriminate and convenient gender-specific WC criteria would be 90 cm for men and 85 cm for women. (Circ J 2009; 73: 1881-1886)

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Background: Little is known about high-density lipoprotein-cholesterol (HDL-C) trajectory patterns among ethnic Chinese in Taiwan, or the effects of lifestyle and biochemical measurements on these trajectory patterns. Methods and Results: This longitudinal study was based on 330 adult participants who underwent biochemical measurements annually from 2003 to 2006. As time progressed, HDL-C increased significantly; women had a consistently higher value (10 mg/dl) than men. An increase of 1 kg/m² in body mass index was associated with -1.00 ±0.25 mg/dl HDL-C for women (P=0.0001) and -0.78 ±0.11 mg/dl for men (P<0.0001). Current smoking was inversely associated with HDL-C in men only. Systolic blood pressure and exercisefrequency were positively associated with HDL-C in men only. Compared with non-smokers, participants who smoked had a lower HDL-C level of -8.42 ±4.90 mg/dl in women (P=0.09) and -3.60 ±0.94 mg/dl in men (P=0.0001). In contrast, a 1-h increase in exercise frequency every week was related to an increased HDL-C level of 0.38 ±0.28 mg/dl for women (P=0.18) and 0.53 ±0.14 mg/dl for men (P=0.0001). Conclusions: An increase in HDL-C was shown over a 4-year period and gender-specific lifestyle factors were associated with HDL-C concentration among ethnic Chinese in Taiwan. (Circ J 2009; 73: 1887-1892)

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Background: Heart failure (HF) with preserved ejection fraction (EF) is common. We compared the characteristics, treatments, and outcomes in HF patients with reduced vs preserved EF by using the national registry database in Japan. Methods and Results: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) is a prospective observational study in a broad sample of patients hospitalized with worsening HF. The study enrolled 2,675 patients from 164 hospitals with an average of 2.4 years of follow-up. Patients with preserved EF (EF ≥50% by echocardiography; n=429) were more likely to be older, female, have hypertension and atrial fibrillation, and less likely to have ischemic etiology compared with those with reduced EF (EF <40%; n=985). Unadjusted risk of in-hospital mortality (6.5% vs 3.9%; P=0.03) and post-discharge mortality (22.7% vs 17.8%; P=0.058) was slightly higher in patients with preserved EF, which, however, were not different after multivariable adjustment. Patients with preserved EF had similar rehospitalization rates (36.2% vs 33.4%; P=0.515) compared with patients with reduced EF. Conclusions: HF patients with preserved EF had a similar mortality risk and equally high rates of rehospitalization as those with reduced EF. Effective management strategies are critically needed to be established for this type of HF. (Circ J 2009; 73: 1893-1900)

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Background: Anemia is common in patients with heart failure (HF) and is associated with worse outcomes. However, the effects of anemia are unknown in an unselected group of HF patients encountered in routine clinical practice in Japan. The impact of anemia on long-term outcomes including mortality and rehospitalization among patients hospitalized with HF was thus assessed. Methods and Results: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) prospectively studied the characteristics and treatments in a broad sample of patients hospitalized with worsening HF and the outcomes were followed. Study cohorts (n=1,960) were classified into 4 groups by discharge hemoglobin quartiles: <10.1 g/dl (n=482), 10.1-11.9 g/dl (n=479), 12.0-13.6 g/dl (n=487), and ≥13.7 g/dl (n=512). Of the total cohort of HF patients, 57% had anemia, defined by using the World Health Organization definition. Patients with lower hemoglobin quartiles had higher rates of all-cause death, cardiac death, and rehospitalization due to worsening HF. After multivariable adjustment, the risk for all-cause death, cardiac death, and rehospitalization significantly increased with low hemoglobin concentrations. Conclusions: Anemia was quite common especially in patients with HF encountered in routine clinical practice in Japan, and lower hemoglobin was independently associated with long-term adverse outcomes in these patients. (Circ J 2009; 73: 1901-1908)

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Background: Stellate ganglion block (SGB) is performed for the diagnosis and treatment of sympathetic dependent pain in the head, neck and upper limbs. However, the effects of bilateral SGB on cardiovascular and autonomic regulation remain unknown. The aim of this study was to assess the effects of bilateral SGB on cardiovascular and autonomic function by measuring heart rate variability (HRV), systolic blood pressure variability (SBPV) and spontaneous baroreflex sensitivity (SBRS). Methods and Results: Twenty healthy volunteers were randomly allocated to receive right or left SGB with 8 ml 1% lidocaine solution; after 20 min, the contralateral side SGB was performed. Changes in the RR interval (RRI), systolic blood pressure (SBP), HRV, SBPV and SBRS were assessed before and after bilateral SGB. The low-frequency (LF, 0.04-0.15 Hz) and high-frequency (HF, 0.15-0.4 Hz) components of HRV and SBRS decreased significantly; however, no significant changes were found in RRI, SBP and the LF and HF components of SBPV after bilateral SGB. In subjects with symptoms of vagal blockade, HRV, SBP and SBRS were significantly affected by bilateral SGB. Conclusions: Bilateral SGB should be performed cautiously because it can reduce cardiac vagal modulation and BRS, especially for those with symptoms of vagal blockade after bilateral SGB. (Circ J 2009; 73: 1909-1913)

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Background: Dendritic cells (DCs) stimulate T-cells to participate in the inflammatory processes that promote the destruction of vulnerable plaques. The relationship between circulating levels of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in patients with acute coronary syndrome (ACS) was evaluated. Methods and Results: Blood samples were obtained from 39 patients with ACS, 41 patients with stable angina pectoris (SAP) and 43 controls. The proportion of mDCs tended to be lower in the ACS group than in the SAP group and controls. Interleukin-12 levels associated with mDCs were significantly higher in the ACS group than in control group. The proportion of pDCs was significantly lower in the ACS groups than in the other two groups. Interferon-α levels secreted by pDCs, however, were not significantly different among the 3 groups. The ratio of mDCs to pDCs ≥4 is an important value for distinguishing ACS from SAP patients and control patients through receiver operating characteristic analysis (sensitivity; 85.0%, specificity; 83.4%). Conclusions: The ratio of mDCs to pDCs may be a useful marker for detecting ACS and the existence of vulnerable plaques. (Circ J 2009; 73: 1914-1919)

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Background: Erythropoietin (EPO) has been shown to have effects beyond hematopoiesis, such as prevention of cardiac apoptosis. The purpose of the current study is to examine the influence of the time-course change in the serum concentration of endogenous EPO on cardiac functions in the chronic phase in patients with acute coronary syndrome, who successfully achieved reperfusion by primary percutaneous coronary intervention (PCI). Methods and Results: The prospective study included 34 patients with angiographically documented coronary artery disease, including 24 patients with acute myocardial infarction (AMI) and 10 patients with unstable angina pectoris (UAP) who underwent successful PCI within 24 h from the onset. Serum EPO concentration significantly increased at Day 3 and Day 7 compared with that at Day 1 in the AMI group, and the level at Day 3 was significantly higher in the AMI group than in the UAP group. There were significant correlations between ΔEPO and Δ left ventricular ejection fraction (LVEF) or Δ left ventricular end-diastolic volume index and between peak EPO concentration and ΔLVEF. Conclusions: These data showed the time-dependent increase of serum EPO in AMI patients after primary PCI, indicating its possible contribution to cardioprotective effect in the chronic phase. (Circ J 2009; 73: 1920-1926)

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Background: The relationship between the epicardial fat volume measured by 64-slice multidetector computed tomography (MDCT) and the extension and severity of coronary atherosclerosis was investigated. Methods and Results: Both MDCT and conventional coronary angiography (CAG) were performed in 71 consecutive patients who presented with effort angina. The volume of epicardial adipose tissue (EAT) was measured by MDCT. The severity of coronary atherosclerosis was assessed by evaluating the extension of coronary plaques in 790 segments using MDCT data, and the percentage diameter stenosis in 995 segments using CAG data. The estimated volume of EAT indexed by body surface area was defined as VEAT. Increased VEAT was associated with advanced age, male sex, degree of metabolic alterations, a history of acute coronary syndrome (ACS) and the presence of total occlusions, and showed positive correlation with the stenosis score (r=0.28, P=0.02) and the atheromatosis score (r=0.67, P<0.0001) of the coronary arteries. Multiple logistic regression analysis revealed an increased VEAT (≥50 cm³/m²) to be the strongest independent determinant of the presence of total occlusions (odds ratio 4.64, P=0.02). Conclusions: VEAT correlates with the degree of metabolic alterations and coronary atheromatosis. Excessive accumulation of EAT might contribute to the development of ACS and coronary total occlusions. (Circ J 2009; 73: 1927-1933)

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Background: The protective effect of +45T >G polymorphism in the adiponectin gene (ADIPOQ) on coronary artery disease (CAD) has been demonstrated in European populations, so this study investigated the effect of +45T >G polymorphism on the risk of CAD and its interactions with other metabolic risk factors in a Chinese population. Methods and Results: The +45T >G polymorphism (rs2241766) of ADIPOQ was genotyped in 600 patients with angiographically diagnosed CAD and in 718 controls. The G allele at the +45T >G polymorphism was associated with a lower risk of CAD (odds ratio (OR), 0.76; 95% confidence interval (CI), 0.64-0.89; P=0.001). The protective effect of the G allele at +45T >G polymorphism was magnified at blood pressure <140/90 mmHg (OR, 0.65; 95%CI, 0.51-0.82; P=0.0004), but disappeared at blood pressure ≥140/90 mmHg (OR, 0.98; 95%CI, 0.76-1.28; P=0.93), indicating an interaction between +45T >G polymorphism and blood pressure on CAD risk (P=0.02 for interaction). A similar interaction was also observed between plasma cholesterol level and the +45T >G polymorphism. Conclusions: An association of ADIPOQ genetic polymorphism with CAD risk is modified by traditional risk factors, such as blood pressure and plasma cholesterol level. (Circ J 2009; 73: 1934-1938)

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Background: The distribution of left ventricular (LV) fibrosis and the percent fibrosis in patients with dilated cardiomyopathy (DCM) were evaluated using late gadolinium enhanced (LGE) MRI. Then the relation with the LV ejection fraction (EF) and deceleration time (DT), an index of diastolic function obtained using echocardiography, was investigated. Methods and Results: LGEMRI at 20 min after intravenous injection of Gd-DTPA (0.15 ±0.03 mmol/kg) was performed in 17 patients with DCM. The distribution of the LV enhanced area and LGE rate (%) were calculated. EF, as well as E/A ratio and DT were obtained using echocardiography. LGE was observed in 15 out of 17 patients (88%) and the enhanced region appeared to represent myocardial fibrosis. The LV fibrosis was often found in the intraventricular septum (IVS), but there were no differences in its distribution. The LGE rate (%) had a correlation between cardiac magnetic resonance ejection fraction (CMREF) (Y = 51.7 - 2.1X [R² = 0.23, P<0.001]) and DT (Y = 162.2 +12.0X [R² = 0.35, P<0.001]). Conclusions: The LV fibrosis is often found in the IVS with DCM. A correlation exists between LGE rate (%) to EF on CMR and DT on echocardiography in patients with DCM. (Circ J 2009; 73: 1939-1944)

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Background: The diagonal ear-lobe crease (ELC) is reported to be a marker of cardiovascular disease. Very few reports have assessed the relationship of ELC with atherosclerosis. This relationship is investigated here using a Japanese population. Methods and Results: A prospective cross-sectional study included 212 consecutive patients. Bilateral ear lobes were checked for the ELC and this was followed by carotid ultrasonography to measure the far wall common carotid artery intima-media thickness (CCA-IMT), plaque score (PS) and plaque number (PN). Patients with ELC had significantly higher carotid IMT than controls (0.90 ±0.24 vs 0.77 ±0.15, respectively, P<0.001). ELC presence correlated significantly with carotid IMT, PS, and PN (r=0.306, P<0.0001; r=0.198, P<0.008 and r=0.221, P<0.0001, respectively), and also with age, male sex and hypertension. ELC presence and absence in mild or no PS and moderate or severe PS subgroups was significant, with a chi-squared value of 7.59 (P<0.006). In multivariate regression analysis, ELC presence correlated with CCA-IMT independently. The odds ratio for the presence of ELC in patients with CCA-IMT of <0.8 mm vs patients with CCA-IMT of ≥0.8 mm (the median value) was 0.41 (95% confidence interval, 0.22-0.76). Conclusions: The present study showed an association between ELC and increased CCA-IMT, PS, and PN. (Circ J 2009; 73: 1945-1949)

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Background: Patients with orthostatic hypotension have pathologic hemodynamics related to changes in body posture. A new cephalic laser blood flowmeter that can be worn on the tragus to investigate the hemodynamics upon rising from a sitting or squatting posture was developed. Methods and Results: The relationship between cephalic hemodynamics and cerebral ischemic symptoms in 63 subjects in a sitting, squatting, and standing positions using the new device was evaluated. Transient decrease in blood pressure within 15 s after rising to an erect position possibly causes dizziness, syncope, and fall. Subjects exhibiting dizziness upon standing showed a significant decrease in the cephalic blood flow (CBF) and indirect beat-to-beat systolic blood pressure, as monitored by the Finometer, and a significant correlation was observed between the drop ratio (drop value on rising/mean value in the squatting position) of CBF and that of systolic blood pressure. Conclusions: This new wearable CBF-meter is potentially useful for estimating cephalic hemodynamics and objectively diagnosing cerebral ischemic symptoms of subjects in a standing posture. (Circ J 2009; 73: 1950-1955)

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A 62 year-old female hemodialysis patient underwent parathyroidectomy to treat secondary hyperparathyroidism. On the preoperative assessment, the plasma levels of parathyroid hormone (PTH) and B-type natriuretic peptide (BNP) were elevated. Echocardiography showed reduced left ventricular (LV) contraction. Myocardial iodine-123-15-(p-iodophenyl)-3-(R,S) methylpentadecanoic acid (¹²³I-BMIPP) scintigraphy showed moderately reduced tracer uptake in the postero-inferior area on single-photon emission computed tomography and decreased washout on the planar images. After parathyroidectomy, the plasma levels of PTH and BNP decreased, followed by improvement in LV contraction. Myocardial ¹²³I-BMIPP scintigraphy revealed that the washout on planar images had increased, which suggests that myocardial ¹²³I-BMIPP scintigraphy is useful for estimating the effect of parathyroidectomy on cardiac function. (Circ J 2009; 73: 1956-1960)

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A 57-year-old Taiwanese man with a past history of variant angina developed simultaneous anterior and inferior myocardial infarction, atrioventricular block, cardiogenic shock, and eventually ventricular fibrillation. Left coronary angiography revealed simultaneous occlusion of the left anterior descending and the left circumflex coronary arteries, which was relieved by intracoronary administration of isosorbide dinitrate. This is the first report of such a case in the English-language medical literature. (Circ J 2009; 73: 1961-1964)

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Pulmonary arterial hypertension (PAH) is a rare complication of glycogen storage disease (GSD), and several cases with a poor outcome have been reported. A 17-year-old boy, who was diagnosed with GSD at 1 year of age, complained of shortness of breath on exertion, and was diagnosed with PAH based on the echocardiographic findings. Beraprost sodium (BPS) was started, and his symptoms improved after 3 months of treatment. Eighteen months later, he experienced frequent episodes of syncope. Because increasing the dose of BPS was ineffective, he was admitted to hospital. The echocardiogram showed marked elevation of the right ventricular pressure and low cardiac output, and his symptoms deteriorated despite continuous infusion of olprinone hydrochloride. Because a single dose of sildenafil increased his cardiac output, treatment with 25 mg sildenafil twice daily was started. His symptoms gradually ameliorated, and 3 weeks later he left the hospital. Two months after starting sildenafil, the cardiac index and the serous B-type natriuretic peptide concentration had become normal. Sildenafil may be effective in patients with secondary PAH and in patients who have developed tolerance to BPS. (Circ J 2009; 73: 1965-1968)

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Restenosis still occurs, even with the sirolimus-eluting stent (SES), and the precise mechanisms have not yet been elucidated. In the present case, focal in-stent stenosis was discovered on angiography 16 months after SES implantation. Intravascular ultrasound revealed an echolucent homogeneous zone, which has been termed "black hole". A sample of stenotic tissue retrieved by aspiration revealed neointimal hyperplasia, composed of proteoglycans and smooth muscle cells with scanty cellularity. Furthermore, infiltration of many macrophages and T lymphocytes coexisted in the restenotic tissue. These findings suggest that delayed healing is 1 of the mechanisms of SES restenosis. (Circ J 2009; 73: 1969-1971)

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(Circ J 2009; 73: 1248-1254)

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