Background The REduction of Atherothrombosis for Continued Health (REACH) Registry is an international observational study of patients with, or at risk of, atherothrombotic disease. Japanese patients were analyzed to clarify national prevalence and treatment. Methods and Results Almost 68,000 outpatients were recruited worldwide with 5,193 in Japan. Among the Japanese patients, 83.7% had established vascular disease (symptomatic) and 16.3% had risk factors only (asymptomatic). Of the symptomatic patients, 14.0% had atherothrombotic lesions in more than 1 vascular bed, with 0.8% having lesions in 3 areas: brain, heart, and peripheral arteries. The prevalence of additional atherothrombotic risk factors among symptomatic patients was independent of the vascular lesion. Obesity was recorded in 10.6% and 42.1% of patients according to the National Cholesterol Education Program and Japanese guidelines, respectively. Pharmacologic intervention for risk factors was inadequate: only 37.7% of diabetic patients received antidiabetic medication, 79.6% of hypertensive patients used antihypertensives, and 74.0% received antiplatelet agents. The use of statins (44.1%) and aspirin (54.7%) was less common than seen in REACH globally. Conclusions Japanese patients enrolled in REACH share many similarities with the global population, but with some important differences. Long-term follow-up will determine the impact of these factors on the development of atherothrombotic events. (Circ J 2007; 71: 995 - 1003)

View full abstract

Background The prevalence of congestive heart failure (CHF) is increasing with the aging of the community. Management of patients with systolic dysfunction (SD) is important for prevention of CHF, but there is little information regarding the burden of SD on Japanese communities. Methods and Results In order to delineate the epidemiological and clinical characteristics of SD patients, the medical records of patients from Sado Island were collected and summarized in 2003. From the 5 years prior to 2003, data for 497 patients were extracted. The mortality rate was significantly higher compared with the general population; and the total number of survivors had decreased to 410 by 2003. The proportion of SD patients in the general population increased sharply after the age of 65 years in males and 70 years in females, reaching 3.3% and 1.7% for men and women, respectively, in their 80 s. In 49% of the patients, the Charlson comorbidity index was ≥2, whereas 24% of females led a solitary life. Conclusions The total count of outpatients with SD is progressively increasing with age. These patients have multiple comorbidities, making the outcome of SD a poor one. The gender difference in disease characteristics and living conditions should be taken into consideration when establishing preventive strategies for CHF in Japanese communities. (Circ J 2007; 71: 1004 - 1012)

View full abstract

Background The incidence of diastolic heart failure (DHF) is increasing with the aging of the community and identifying patients with isolated diastolic dysfunction (IDD) is important for preventing DHF. However, very little information is available about such patients in the Japanese community. Methods and Results The medical information of all outpatients with moderate to severe IDD was extracted from the records of approximately 6,948 individuals who underwent echocardiographic (Echo) examinations during the past 5 years in Sado Island. Of the 284 patients extracted, 272 survived until 2003. In January 2003 the proportion of patients with moderate to severe IDD in the general population sector aged 45-84 years was 0.9% for males and 0.5% for females, and this proportion increased sharply after the age of 65 in both genders, reaching 1.6% for men in their 70 s and 0.8% for women in their 80 s. On Echo, 165 patients (61%) showed hypertrophic left ventricular geometry. The Charlson comorbidity index score was ≤1 in 63% of patients. The cumulative survival of IDD patients, irrespective of a history of congestive heart failure (HF), was significantly lower than in the general population. Conclusions Moderate to severe IDD is not uncommon in the elderly and has a poor prognosis. Characteristics of outpatients with IDD should be taken into consideration when establishing a preventive strategy for HF in the Japanese community. (Circ J 2007; 71: 1013 - 1021)

View full abstract

Background The purpose of the study was to characterize the pharmacokinetics of mycophenolic acid (MPA) in Japanese heart transplant recipients and to find the time point that has the best correlation with the MPA area under the plasma concentration curve (AUC). Methods and Results Twenty-two Japanese recipients treated with mycophenolate mofetil were evaluated in the study. Approximately 9 months after transplantation, the area under the MPA serum concentration-time curve from 0 to 12 h (AUC_{0-12 h}) was evaluated. The MPA AUC_{0-12 h} h values in the cyclosporine (CsA) and tacrolimus (FK) groups ranged from 13.11 to 50.98 μg · h/ml and from 39.19 to 93.18 μg · h/ml, respectively. Fourteen models were developed and analyzed for their ability to estimate the MPA AUC_{0-12 h} based on a limited number of samples in the CsA group. Sixteen models were developed in the FK group. The best model for predicting the full MPA AUC_{0-12 h} in the CsA group was a 3-time-point model that included C_{0 h}, C_{1 h} and C_{2 h} (r², 0.96; mean prediction error, 0.15±7.85%); a 2-time-point model that included C_{0 h}, and C_{2 h} (r², 0.94; mean prediction error, 0.495±10.35%) was also reliable. In the FK group, a 3-time-point model that included C_{1 h}, C_{2 h} and C_4h (r², 0.73; mean prediction error, 2.73±17.09%) was the best model for predicting the full MPA AUC_{0-12 h}, but it was not reliable in clinical practice. Conclusion A 3-(C_{0 h}, C_{1 h} and C_{2 h}) and a 2-time-point model (C_{0 h} and C_{2 h}) are useful for predicting the full MPA AUC_{0-12 h} in Japanese heart transplant recipients treated with CsA but not with FK. (Circ J 2007; 71: 1022 - 1028)

View full abstract

Background Although electrocardiogram-gated single-photon emission computed tomography (SPECT) may be useful in risk stratification of elderly patients with coronary artery disease (CAD), few studies have prospectively evaluated its prognostic value in this patient population. Methods and Results A total of 175 patients aged 75 years or more with known or suspected CAD were prospectively evaluated by stress gated SPECT using a 20-segment model and an automatic functional analysis. Patients with acute coronary syndrome within the previous 3 months, and those who underwent coronary revascularization within 3 months after the SPECT study were excluded. Outcome assessment included prespecified cardiac events and noncardiac deaths. During a mean follow-up of 3.4 years, there were 18 cardiac events: 2 cardiac deaths, 1 nonfatal myocardial infarction, 3 coronary artery bypass grafting, 5 percutaneous coronary interventions, 1 unstable angina, 4 heart failures, and 2 malignant arrhythmias. Kaplan-Meier survival estimation indicated an event-free survival rate of 98.1% at 3 years in patients without myocardial ischemia, but 79.9% in those with ischemia as documented by gated SPECT (p=0.0001). Multivariate analysis using the Cox proportional hazard model demonstrated that stress-induced myocardial ischemia was the only independent predictor for subsequent cardiac events (p<0.01). Conclusions Stress gated SPECT predicts cardiac events in patients aged 75 years or more with known or suspected CAD and may have a role in risk stratification of this patient population. (Circ J 2007; 71: 1029 - 1034)

View full abstract

Background Exercise training (ET) is an emerging therapy for chronic heart failure, but the baseline patient characteristics for predicting cardiac events (CEs) during the course of ET remain unknown. Methods and Results Of the 111 stable heart failure patients who participated in a 3-month ET program, 6 withdrew from the program for cardiac reasons and 9 had transient interruptions in the program because of CEs. The baseline clinical characteristics of these 15 patients (CE group) and the remaining 96 patients (No-CE group) were compared. Compared with the No-CE group, the CE group had a significantly higher prevalence of pacemaker/implantable cardioverter-defibrillators, larger left ventricular end-diastolic diameter (LVEDDs), lower peak oxygen uptake, greater ventilation drive, and higher plasma brain natriuretic peptide concentration at baseline. Multivariate logistic regression analysis showed that a larger LVEDD was a significant predictor of the occurrence of a transient interruption to or permanent withdrawal from the ET program because of CEs. Receiver operating characteristic curve analysis demonstrated that an LVEDD ≥65 mm had a sensitivity of 93% and specificity of 48% in predicting CEs. Conclusions Patients with a large LVEDD (≥65 mm) at baseline should be monitored carefully during the course of an ET program. (Circ J 2007; 71: 1035 - 1039)

View full abstract

Background Oxidative stress plays an important role in the pathogenesis of heart failure and was investigated in the present study of the role of exogenous A-type natriuretic peptide (ANP) in the patients with heart failure and in cultured neonatal rat cardiomyocytes. Methods and Results The first protocol was to examine if an infusion of human ANP (carperitide) changed serum levels of TRX (thioredoxin) during the treatment of patients with heart failure compared with conventional therapy using furosemide. Protocol 2 investigated whether ANP had a direct antioxidant action on the failing heart by measuring TRX gene expression and reactive oxygen species (ROS) production in cultured neonatal rat cardiomyocytes. In Protocol 1, 8 patients were treated with only an intravenous bolus of furosemide and 11 patients with only an intravenous infusion of carperitide for 24 h. Serum TRX levels significantly decreased at 4 h (p<0.03) and at 24 h (p<0.05) in the carperitide group, whereas they decreased slightly but were not significantly different in the furosemide group. In Protocol 2, it was found that a low dose of exogenous ANP of 10-9 mol/L significantly suppressed TRX expression and ROS production in cardiomyocytes. Conclusion Carperitide infusion has a predominantly antioxidant action, in addition to improving the hemodynamics of patients with acute heart failure. Furthermore, carperitide infusion should have a direct antioxidant effect on the failing heart. (Circ J 2007; 71: 1040 - 1046)

View full abstract

Background Persistently increased serum concentrations of cardiac troponin (cTn) are a prognostic marker in patients suffering from chronic congestive heart failure (CHF), but the significance in acute cardiac decompensation is unclear. Methods and Results Serial blood samples were collected from 52 patients presenting with acute cardiac decompensation in the absence of an acute coronary event. Serial serum concentrations of cTnI, creatine kinase (CK)-MB, and brain natriuretic peptide (BNP) were measured by rapid assay. BNP and CK-MB steadily decreased from 902±529 pg/ml and 2.3±1.6 ng/ml at baseline to 453±427 pg/ml and 1.2±1.6 ng/ml on day 7, respectively, (p<0.0001 for both comparisons). In contrast, cTnI did not decrease significantly and, in 17 patients (35%), increased from 0.063±0.047 ng/ml at baseline to 0.167±0.181 ng/ml on day 1 (p<0.05). By single variable regression analysis, systolic blood pressure (SBP), use of inotropes or inodilators, vasodilators, and an initially elevated cTnI were predictors of elevated cTnI on day 1. By multiple variable analysis, an elevated SBP (as a mitigating factor) (odds ratios (OR) 0.12; 95% confidence intervals (CI): 0.02-0.76; p=0.0248), and high baseline cTnI (OR 13.85; 95%CI: 1.97-97.54; p=0.0083) were significant predictors of an elevated cTnI on day 1. Patients with elevated cTnI on day 1 had higher rates of worsening CHF and death from CHF than patients without such an increase (p<0.05). Conclusions Persistently increased serum concentrations of cTn in patients with acutely decompensated heart failure are predictive of adverse outcomes. (Circ J 2007; 71: 1047 - 1051)

View full abstract

Background The inflammatory mediators play an important role in the progression of coronary vasculitis in Kawasaki disease (KD), but effects of KD serum including inflammatory mediators on endothelial cells remain unknown. We hypothesized that serum activity to stimulate in vitro human umbilical vein endothelial cells (HUVEC) tube formation might be impaired in KD. Methods and Results Serum from patients with coronary aneurysms was less active in stimulating HUVEC tube formation than serum from patients without coronary aneurysms or febrile controls. In patients with coronary aneurysms, the reduction in the serum angiogenic activity was documented already before KD treatment (p=0.03 vs healthy controls, p=0.08 vs febrile controls) and enhanced after intravenous immune globulin plus aspirin (p<0.001 vs healthy controls, p=0.002 vs febrile controls); both drugs did not affect the assay studied. This reduction was greater in patients who later developed giant aneurysms >8 mm compared with those who developed small to moderate aneurysms (p=0.01). The reduced serum angiogenic activity was partly caused by the reduction in the serum activity of stimulating HUVEC proliferation. Conclusions Serum activity to stimulate HUVEC tube formation was impaired in KD patients who later developed larger coronary aneurysms, which may be associated with the severity of vascular injury. (Circ J 2007; 71: 1052 - 1059)

View full abstract

Background Gender differences in the predictors of outcome among patients with known or suspected coronary artery disease (CAD) undergoing contrast-enhanced dobutamine stress echocardiography (CE-DSE) have not been completely determined. Methods and Results Follow-up (30±17 months) data for 581 men and 309 women with known or suspected CAD who underwent CE-DSE (mean age: 66 years) were obtained. Hard cardiac events included cardiac death and nonfatal myocardial infarction. Total cardiac events included hard cardiac events, unstable angina, congestive heart failure, and late revascularization (>3 months). Cardiac events occurred in 123 male and 50 female patients. Positive results for CE-DSE were associated with worse prognosis in both men and women (2-year total event free rate: 73.5% vs 88.2% in men, p<0.0001, 80.3% vs 91.3% in women, p<0.01). Addition of CE-DSE results, including abnormal left ventricular end-systolic volume response and left ventricular ejection fraction at peak stress <50%, to the clinical and rest echocardiography model provided incremental information for predicting total cardiac events (increase in chi-square value for the model from 60 to 72, p<0.001) in men and (increase in chi-square value for the model from 17 to 32, p<0.001) in women. Conclusions CE-DSE provides incremental information for predicting future cardiac events in both men and women. (Circ J 2007; 71: 1060 - 1066)

View full abstract

Background Glycated albumin is the predominant circulating Amadori-type glycated protein in vivo and plays a major role in the development of diabetic vascular complications. The aim of this study was to assess the relationship between increased serum glycated albumin level and the presence and severity of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). Methods and Results In a total of 320 consecutive patients with T2DM, coronary angiography revealed normal coronary arteries in 83 patients (control group) and significant coronary stenosis (≥70% luminal diameter narrowing) in 237, of whom 51 patients had 1-vessel disease (Group I), 80 had 2-vessel disease (Group II), and 106 had 3-vessel disease (Group III). Serum glycated albumin, hemoglobin A_1c (HbA_1c) and tumor necrosis factor (TNF)-α levels, lipid profile, and renal function were measured. Logistic regression analysis was performed to determine the relative risk of serum glycated albumin level for the presence and severity of CAD. Multivariate stepwise linear regression analysis was done to identify independent determinants of the glycated albumin level. Serum glycated albumin (21.2±5.3% vs 19.4±4.3%, p=0.005) and TNF-α levels (123 ±115 pg/ml vs 65±59 pg/ml, p<0.001) were significantly higher in patients with CAD than in controls, but serum HbAlc level did not significantly differ between them (7.6±1.3% vs 7.4±1.2%, p=0.19). There was a significant difference in serum glycated albumin level between Groups I and III (19.5±3.3% vs 21.8±5.7%, p<0.001). The serum glycated albumin level correlated with the number of diseased arteries (Spearman r=0.205, p<0.001), and was closely related to serum levels on admission of glucose (r=0.495, p<0.001), TNF-α (r=0.123, p=0.028), blood urea nitrogen (r=0.167, p=0.004), triglycerides (r=0.129, p=0.021), and HbA_1c (r=0.795, p<0.001). Multivariate analysis indicated that serum levels of glucose (p<0.0001), TNF-α (p=0.001), blood urea nitrogen (p=0.004) and triglycerides (p=0.035) were independent determinants for glycated albumin. Logistic regression analysis revealed that glycated albumin ≥19% (odds ratio (OR) 2.9, p<0.001) was an independent predictor for CAD and glycated albumin ≥21% (OR 2.3, p=0.032) for 3-vessel disease prediction. The area under the receiver-operating characteristic curve for glycated albumin (0.620, 95% confidence interval (CI) 0.548 to 0.691, p=0.001) was superior to that for HbA_1c (0.543, 95% CI 0.473 to 0.613, p=0.243). Conclusions An increased serum level of glycated albumin is associated with the presence and severity of CAD, and may be useful in screening patients with T2DM. (Circ J 2007; 71: 1067 - 1073)

View full abstract

Background Coronary spasm plays an important role in the pathogenesis of ischemic heart disease and it may be associated with low-grade inflammation. Methods and Results Intracoronary injection of acetylcholine was done in 199 patients (99 men, 100 women, mean age, 64.5±11.0 years) with chest pain and normal coronary angiograms. According to the results of the provocation test, the study subjects were divided into 2 groups: the spasm group of 112 patients and the non-spasm group of 87 patients. Clinical data including high-sensitivity C-reactive protein (hs-CRP) and other coronary risk factors were compared between the 2 groups. Serum levels of hs-CRP were significantly higher in the spasm group than in the non-spasm group (median: 1.2 mg/L vs 0.5 mg/L, p<0.005). Multivariate analysis showed that hs-CRP and smoking history were independently associated with coronary spasm with an odds ratio of 2.28 (p=0.027) and 2.25 (p=0.037), respectively, with a hs-CRP value of ≥2 mg/L as cutoff point. Conclusions Minor elevations of the serum hs-CRP level are significantly associated with coronary spasm, suggesting that chronic low-grade inflammation may be involved in the pathogenesis of coronary spasm. (Circ J 2007; 71: 1074 - 1078)

View full abstract

Background Recent studies have shown that a global flow abnormality affects the entire coronary tree in patients with acute coronary syndrome (ACS), and that it is associated with adverse outcomes. Postprandial hyperglycemia is also thought to promote coronary endothelial dysfunction, as well as the release of inflammatory and vasoconstrictive factors. This study used the corrected Thrombolysis In Myocardial Infarction frame count (CTFC) to investigate whether optimal control of postprandial hyperglycemia improves pan-coronary flow. Methods and Results Eighty ACS patients with postprandial hyperglycemia who had successful coronary intervention and who had undergone a 75-g oral glucose tolerance test (OGTT) were included. A second OGTT and angiogram were performed 8 months after procedures. The patients were divided according to postprandial glycemia after the second 75-g OGTT; optimal postprandial hyperglycemia was defined as a 2-h blood glucose concentration <7.8 mmol/L. Changes in the CTFC of culprit/non-culprit arteries, glucose response, and other clinical variables were compared. Forty patients improved to an optimal control at 8 months. In the culprit artery, the 8-month angiogram revealed a significantly improved CTFC among those with optimal control compared with the initial angiogram (30±9 vs 24±12, p<0.05). In contrast, the CTFC was not evidently improved among patients with suboptimal control. The CTFC at 8 months had thus obviously improved more in patients with optimal, than with suboptimal control (24±12 vs 30±11, p<0.05). Conclusion Optimal control of postprandial hyperglycemia improves epicardial blood flow in both arteries and this beneficial effect might be from improved coronary endothelial function. (Circ J 2007; 71: 1079 - 1085)

View full abstract

Background The prognostic value of interleukin (IL)-10 in patients with ST-segment elevation acute myocardial infarction (ST-se AMI) is currently unclear. The purpose of this study was to test whether the serum IL-10 level can predict 30-day mortality in patients with ST-se AMI undergoing primary percutaneous coronary intervention (PCI). Methods and Results The study design was a prospective cohort study of 250 consecutive patients with ST-se AMI of onset <12 h who were undergoing primary PCI. Blood samples for serum IL-10 levels were collected in the catheterization laboratory following vascular puncture. The serum IL-10 level was also evaluated in 20 healthy and 30 at-risk control subjects. The mean serum level of IL-10 was significantly higher in the AMI patients than in either group of controls (all values of p<0.0001). Patients with a high serum IL-10 level (≥30 pg/ml) had a significantly lower left ventricular ejection fraction (LVEF) (defined as <50%), significantly higher incidence of cardiogenic shock, higher white blood cell (WBC) count, more advanced congestive heart failure (defined as New York Heart Association function classification of ≥3), and increased 30-day mortality than those patients with a low serum IL-10 level (<30 pg/ml) (all values of p<0.0001). Multiple stepwise logistic regression analysis demonstrated that a high serum IL-10 level, together with low LVEF, high WBC count and unsuccessful reperfusion, was independently predictive of increased 30-day mortality (all values of p<0.005). Conclusion In patients with ST-se AMI, the serum IL-10 level is a major independent predictor of 30-day mortality and should be used for early risk stratification following acute myocardial infarction. (Circ J 2007; 71: 1086 - 1091)

View full abstract

Background Significant coronary artery disease (CAD) is generally considered as an exclusion criterion for the diagnosis of takotsubo cardiomyopathy (TC). However, this may not be justified in all cases, because TC and CAD may coincide. Methods and Results Among 821 consecutive patients who underwent urgent left heart catheterization for suspected acute coronary syndrome between December 2004 and August 2006 those with a final diagnosis of TC who also had a stenotic lesion (diameter stenosis on quantitative coronary angiography >50% and <75%) of the left anterior descending artery were evaluated. Four patients met the inclusion criteria. Previous coronary angiograms were available for 2 of these patients and showed no change in the angiographic appearance of the lesions. Intravascular ultrasound study was performed in the other 2 patients and demonstrated negative remodeling and no signs of plaque rupture, thrombus, positive remodeling or intimal dissection. Conclusions The present study supports the notion that TC and CAD are not mutually exclusive disease entities. Excluding the diagnosis of TC on the sole basis of an incidental finding of CAD may not be justified in all cases. Rather, a case-by-case decision process seems more appropriate. (Circ J 2007; 71: 1092 - 1094)

View full abstract

Background The present study aimed to investigate the association between low bone mass (LBM) and coronary artery disease (CAD) in male patients. Method and Results The data for 47 men who were screened for osteopenia and osteoporosis with dual energy X-ray absorptiometry and then underwent coronary angiography between February 2005 and May 2006 were retrospectively analyzed. Bone mineral density of the femur neck was stratified as normal (T score >-1.0 SD) or low (T score <-1.0 SD) and CAD was defined as ≥50% occlusion in at least 1 major coronary artery. Thirty-two patients were found to have angiographically significant CAD. Patients in the LBM group had a significantly higher incidence of CAD. Low bone mass was significantly and positively correlated with the Gensini scores of the patients (r=0.6037, p<0.0001) and was found to be an independent predictor of CAD in multivariate logistic regression analysis (odds ratio: 5.4 [95% confidence interval 1.66 and 17.49]; p=0.0049). Repeated statistical analyses with the acceptance of CAD as coronary artery stenosis >75% confirmed the same results. Conclusion Low bone mass was significantly associated with angiographically documented CAD in males. (Circ J 2007; 71: 1095 - 1098)

View full abstract

Background The incidence and mechanism of the dislocated antegrade fast pathway (A-FP) were examined in various forms of atrioventricular nodal reentrant tachycardia (AVNRT). Methods and Results To localize the A-FP, 5 atrial sites comprising the inferior coronary sinus ostium (CSOS), apex of the triangle of Koch (A-TOK), and 3 equidistant sites on the atrioventricular junction extending from A-TOK to CSOS (site S, M, and I) were pace mapped at 100 beats/min in 71 patients with slow-fast (n=49), fast-slow (n=7) and slow-intermediate (n=15) forms of AVNRT. The site with the shortest interval between the stimulus and His potential recorded at the A-TOK (shortest St-H) was defined as the A-FP site. The A-FP was located at A-TOK in 31 patients (nondislocated group), and inferior to A-TOK in 40 patients (site S in 26, M in 13, and I in one patient; dislocated group). There was no significant difference in the location of the A-FP among the 3 forms of AVNRT. Although the shortest St-H did not differ between groups, the St-H at A-TOK in the dislocated group was significantly longer than that in the nondislocated group. Additionally, the His potential preceding that of the A-TOK was observed more frequently inferior to the A-TOK in the dislocated group than in the nondislocated group, suggesting that the A-FP dislocation was accompanied by displacement of the His bundle. Conclusions Dislocated A-FP was frequently and uniformly observed among various forms of AVNRT, and is probably caused by inferior displacement of the entire atrioventricular node - His bundle apparatus. (Circ J 2007; 71: 1099 - 1106)

View full abstract

Background The therapeutic strategy for non-sustained ventricular tachycardia (NSVT), considered as a risk-stratifier for sudden cardiac death (SCD), still remains undetermined. Methods and Results In the present study 222 of 4,079 patients (5.4%) hospitalized with NSVT during 2002 to 2004 were prospectively evaluated using an algorithm for risk-stratification according to each type of structural heart disease. The algorithm comprises the left ventricular ejection fraction, signal-averaged electrocardiography, programmed ventricular stimulation and the family history of SCD. Of the 222 patients, 151 (68.0%) were successfully risk-stratified and 32 patients consequently received an implantable cardioverter defibrillator (ICD) (21.2%; algorithm-ICD group). The remaining 119 patients without an ICD (algorithm-observation group) were observed. During 27.7±11.4 months of follow-up, the patients in the algorithm-ICD group had a significantly higher prevalence of tachyarrhythmic events than did those in the algorithm-observation group (9/32 vs 1/119; p<0.05). In the algorithm-ICD group, 2, 1 and 6 patients experienced an SCD, aborted SCD and appropriate ICD intervention, respectively, while there was only 1 SCD in the algorithm-observation group. Conclusions The proposed algorithm for risk-stratification of patients with NSVT may be feasible for appropriate selection of high-risk patients and candidates for prophylactic ICD implantation. (Circ J 2007; 71: 1107 - 1114)

View full abstract

Background Conversion to sinus rhythm (SR) is rarely attempted in patients with rheumatic atrial fibrillation (AF) because the length of AF duration and the dilation of left atrium (LA) make maintenance of SR difficult. In this study, predictors of the successful maintenance of SR with amiodarone and electrical cardioversion in rheumatic AF patients receiving percutaneous transluminal mitral valvuloplasty (PTMV) were identified Methods and Results This study included 23 consecutive patients undergoing PTMV for rheumatic AF (6 men, 53±11 years; AF duration 25 ±24 months; LA diameter 44±6 mm; mitral valve area (MV) 1.1±0.2 cm²). Electrical cardioversion was required for the successful conversion to SR in all patients regardless of whether they had received amiodarone (400 mg/day) 2 months before PTMV (n=8) or 2 months after (n=15). After cardioversion, all patients received amiodarone 200 mg/day. With a follow-up period of 35±8 months, 14 patients (61%) remained in SR. A greater reduction in LA size (-4±3 mm vs 1±1 mm; p=0.004) and an greater increase in MV area (0.8±0.4 cm² vs 0.5±0.2 cm²; p=0.01) by PTMV, not AF duration, were found to be the independent predictors for patients with successful maintenance of SR as compared with patients with recurrence of AF. Conclusion In rheumatic AF patients receiving PTMV, the successful maintenance of SR with amiodarone and electrical cardioversion can be predicted by the degree to which LA size is reduced and MV area is increased. (Circ J 2007; 71: 1115 - 1119)

View full abstract

Background The prognostic significance of uric acid (UA) levels in acute stroke is unclear, so the objective of this study was to determine the association between levels of serum UA (SUA) and mortality in acute stroke. Methods and Results Consecutive patients (n=435) presenting with ischemic stroke and intracerebral hemorrhage were included in the study. The length of stay in hospital and the occurrence of death were recorded. On univariate analysis, the occurrence of death was associated with older age, smoking, presence of congestive heart failure or atrial fibrillation, absence of hyperlipidemia, and intracerebral hemorrhage as the index event. Furthermore, glucose, urea, creatinine and SUA at admission were significantly higher in patients who died, whereas total and high-density-lipoprotein cholesterol were significantly lower. On multiple logistic regression analysis, the independent relationship between higher SUA levels and death was confirmed (odds ratio (OR), 1.37; 95%confidence interval (CI), 1.13-1.67; p=0.001). The only other variables independently associated with the occurrence of death were urea concentration and presence of atrial fibrillation. If urate was >7.8 mg/dl (0.47 mmol/L), then there would be a high probability of early death (87%). Conclusions Elevated levels of SUA are independently associated with an increased risk of early death in acute stroke. (Circ J 2007; 71: 1120 - 1127)

View full abstract

Background The price disparity between Japan and foreign countries for medical devices is a controversial issue. Price differences existed between Japan and USA for various medical devices in early 2005, so in the present study, a more precise and detailed investigation of the latest market prices of medical devices between Japan and USA was conducted in 2006, focusing on coronary stents and percutaneous transluminal coronary angioplasty (PTCA) catheters, for an evaluation of the efficacy of current Japanese policies. Methods and Results Japanese market prices were obtained from 31 university hospitals, and US market prices were obtained from 1 hospital chain and 2 group-purchasing organizations. The price ratio (Japanese market price/US market price) was determined to be 1.2-1.4 for drug-eluting stents (DES), 1.6-2.4 for non-DES, and 4.1-5.1 for PTCA catheters. Conclusions Results showed that the price disparity was relatively small for DES, but still significant for non-DES and PTCA catheters. Radical measures must be taken to improve the fundamental causes of price disparity and might include reviewing the implementation of the Japanese Pharmaceutical Affairs Law, abolishing the reimbursement price system for medical devices, and establishing centers of clinical excellence. (Circ J 2007; 71: 1128 - 1130)

View full abstract

Background There appear to be sex differences in the risk factors for peripheral arterial disease (PAD) in type 2 diabetic patients, but studies in Taiwanese patients have not been conducted. Methods and Results A total of 610 (268 men, 342 women) Taiwanese patients aged 63.3±10.8 years were evaluated. PAD was diagnosed by an ankle - brachial index <0.9. Risk factors included age, sex, body mass index (BMI), waist circumference (WC), smoking, menopause, diabetes duration, hypertension, insulin therapy, systolic and diastolic blood pressures, fasting glucose, total cholesterol (TC), triglyceride (TG), high- (HDL-C) and low-density lipoprotein-cholesterol (LDL-C), apolipoproteins A1 (ApoA1) and B (ApoB) and uric acid (UA). When compared with the men, the women were significantly older and had longer duration, smaller WC, higher levels of systolic blood pressure, TC, TG, HDL-C, LDL-C, ApoA1 and ApoB, lower levels of UA, fewer smokers and more insulin users. Stepwise logistic regression showed age, BMI (inverse association) and systolic blood pressure as independent risk factors for men [respective odds ratios (OR): 1.080 (1.024-1.139), 0.832 (0.713-0.971) and 1.028 (1.005-1.051)]; and for women they were age, UA and insulin therapy [respective OR: 1.113 (1.056-1.173), 1.340 (1.101-1.630) and 4.173 (1.974-8.824) Conclusions PAD risk factors differ significantly between the sexes. (Circ J 2007; 71: 1131 - 1136)

View full abstract

Background Diuretics are the most prescribed medication for heart failure (HF) patients, but clinical evidence of the long-term effects of diuretics are lacking. The present study was designed to compare the therapeutic effects of furosemide, a short-acting loop diuretic, and azosemide, a long-acting one, in patients with HF to test the hypothesis that long-acting diuretics are superior therapy. Methods and Results The Japanese Multicenter Evaluation of LOng- vs short-acting Diuretics In Congestive heart failure (J-MELODIC) is a multicenter, prospective, randomized trial enrolling a total of 300 patients (150 patients in each group). The primary outcome is a composite of cardiovascular death and unplanned admission to hospital for congestive HF. Other outcomes include all-cause mortality, worsening of the symptoms of HF, or a need for modification of therapy. Serial assessment of echocardiographic and neurohumoral parameters will be conducted over a minimum follow-up period of 2 years. Conclusions The study results will provide important evidence for the treatment of chronic HF. (Circ J 2007; 71: 1137 - 1140)

View full abstract

Background To determine whether mild to moderate ischemia that is not severe enough to induce myocardial infarction will cause myocardial cell damage or apoptosis, the ^99mTc-Annexin-V (Tc-A) uptake was studied in groups of rats with various intervals of coronary occlusion and reperfusion times. Methods and Results After left coronary artery occlusion for 15 min (n=23), 10 min (n=23), or 5 min (n=12), Tc-A (80-150 MBq) was injected at 0.5, 1.5, 6, or 24 h after reperfusion. One hour later, to verify the area at risk, ²⁰¹Tl (0.74 MBq) was injected just after left coronary artery re-occlusion and the rats were killed 1 min later. Dual tracer autoradiography was performed to assess Tc-A uptake and area at risk. In all 5-min occlusion and reperfusion models, no significant Tc-A uptake was observed in the area at risk. Tc-A uptake ratios in the 15-min and 10-min ischemia models were 4.46±3.16 and 2.02±0.47 (p=0.078) at 0.5 h after reperfusion, 3.49±1.78 and 1.47±0.11 (p<0.05) at 1.5 h after reperfusion, 1.60±0.43 and 1.34±0.23 (p=0.24) at 6 h after reperfusion, 1.50±0.33 and 1.28±0.33 (p=0.099) at 24 h after reperfusion, respectively. With 15-min ischemia, in 3 of the 5 rats there were a few micro-foci of myocardial cell degeneration and cell infiltration in less than 1% of the ischemic area at 24 h after reperfusion. No significant histological change was observed in rats with 10-min or 5-min ischemia. Conclusion The data indicate that Tc-A binding depends on the severity of ischemia even without a significant amount of histological change or infarction. (Circ J 2007; 71: 1141 - 1146)

View full abstract

Background Exercise training may protect against the development of atherosclerosis, although the precise mechanisms are still unknown. The present study assessed the hypothesis that exercise training would reduce the severity of experimental atherosclerosis in apolipoprotein-E (apoE)-deficient mice via nitric oxide (NO). Methods and Results ApoE-deficient mice fed a high-fat diet underwent exercise training (30 min swimming) 3 times per week for 8 weeks. The exercise group were also given oral N^G-nitro-L-arginine methylester (L-NAME; 25 mg · kg ^-1 · day^-1), an inhibitor of NO synthase. Fatty streak plaque lesions developed in ApoE-deficient mice fed the high-fat diet, and were suppressed in the mice that underwent swimming training. In contrast, atherosclerotic lesions were not ameliorated in mice that had exercise training plus oral L-NAME treatment. Immunohistochemical analysis revealed that the expression of endothelial NO increased in mice undergoing exercise compared with the mice that did not exercise, and that the expression was suppressed in the mice having exercise plus oral L-NAME treatment. Differences in lesion area did not correlate with any significant alterations in serum lipid levels. Conclusion Exercise training suppressed atherosclerosis via the NO system. (Circ J 2007; 71: 1147 - 1151)

View full abstract

Background Pathological calcification in soft tissues (ie, ectopic calcification) can have severe consequences. Hydroxyapatite is the common mineral phase present in all tissue calcifications. In general, the development of tissue calcifications requires a pre-existing injury as an inducer (heterogeneous nucleant), whereas further progression requires the presence of other promoter factors (such as hypercalcemia and/or hyperphosphatemia) and/or a deficiency in calcification repressor factors (crystallization inhibitors and cellular defense mechanisms). The present study investigated the capacity of etidronate (a bisphosphonate used in osteoporosis treatment) and phytate (a natural product) to inhibit vascular calcification in rats. Methods and Results Six male Sprague-Dawley rats in each of the 3 treatment groups were subcutaneously injected with either a placebo (physiological serum solution), etidronate (0.825 μmol · kg^-1 · day ^-1) or phytate (0.825 μmol · kg ^-1 · day^-1) for 8 days. Four days into this regimen, calcinosis was induced by subcutaneous injections of 500,000 IU/kg vitamin D at 0 h, 24 h and 48 h. Ninety-six hours after the final vitamin D injection, the rats were killed and aortas and their hearts were removed for histological and calcium analyses. The data showed that phytate-treated rats had lower levels of aortic calcium than placebo-treated rats. All groups had similar heart calcium levels. Conclusions The present study found that phytate acted as a vascular calcification inhibitor. Thus, the action of polyphosphates could be important in protecting against vascular calcification. (Circ J 2007; 71: 1152 -1156)

View full abstract

Background Associations between exposure to particulate matter and susceptibility to cardiovascular events have been reported. Although the underlying mechanisms are not fully understood, this association seems to be particularly exaggerated in the presence of atherothrombotic risk factors. The present study was undertaken in low-density lipoprotein receptor knockout (LDLR/KO) mice to test the hypothesis that long-term exposure to a high dose of nano-sized carbon black (CB) exacerbates atherosclerotic lesions. Methods and Results LDLR/KO mice were subjected to a 10-week intratracheal dispersion of CB (1 mg/week) or air under a 0% or 0.51% cholesterol (Chol) diet. Development of aortic lipid-rich lesions was detected in mice under a 0.51% Chol diet with or without CB dispersion, but not in mice fed a 0% Chol diet with or without CB. Quantification of the area stained with oil red O revealed the highest percentage in CB-treated mice on a 0.51% Chol diet among the 4 groups. One-way ANOVA indicated CB-treated mice with 0.51% Chol diet had a significantly higher percentage of positive staining than vehicle-treated mice with 0.51% Chol diet (p<0.05). Conclusions In LDLR-deficient mice under a high Chol diet, exposure to CB resulted in acceleration of development of atherosclerosis. (Circ J 2007; 71: 1157 - 1161)

View full abstract

Though stenoses of the descending aorta and its branches are seen with congenital anomalies or systemic inflammation, occlusion of the descending aorta is extremely rare. A patient with an occluded hypoplastic descending thoracic aorta required re-operation because of graft failure between the descending thoracic aorta and the infrarenal abdominal aorta. The etiology of the aortic occlusion in this case is unknown, but inflammation, such as Takayasu disease, is speculated. (Circ J 2007; 71: 1162 - 1163)

View full abstract

A 35-year-old man was referred to Nihon University Hospital because of repetitive ventricular tachycardia (VT) at 180-200 beats/min. QRS morphology of the VT was right bundle branch block with a northwest axis. Transthoracic echocardiography showed hypertrophic cardiomyopathy. Coronary angiography was normal and left ventriculography showed neither obstruction in the left ventricle (LV) nor any pressure gradients within the LV or between the LV and aorta. Hemodynamic deterioration occurred during VT. Intracardiac mapping showed that the VT originated from the posteroseptal portion of the LV near the apex and Purkinje potentials that preceded the onset of the QRS complex by 58-70 ms were documented. Radiofrequency ablation at these sites terminated the VT, which has not recurred for 25 months. (Circ J 2007; 71: 1164 - 1168)

View full abstract

Transthoracic 2-dimensional (D) echocardiography (echo) is often used to assess tricuspid regurgitation (TR) after implantation of permanent pacemakers. However, its ability to define the precise anatomical relationship between the tricuspid valve and the pacemaker lead is quite limited. This report presents a 58-year-old male with aggravation of TR after pacemaker implantation for heart block. Three-D echo precisely depicted the entrapment of the lead shaft in the fused and fibrotic septal and posterior tricuspid leaflets. The patient underwent tricuspid valve annuloplasty and the symptoms of right heart failure improved soon after the operation. (Circ J 2007; 71: 1169 - 1171)

View full abstract