Background While stent restenosis and late thrombosis still occur even with drug-eluting-stents (DES), there remains a need to explore other strategies for preventing restenosis. Methods and Results Five hundred and twenty-one patients were randomized: 260 to cutting-balloon angioplasty (CBA) before bare-metal stent (CBA-BMS) and 261 to balloon-angioplasty (BA) before BMS (BA-BMS). Intravascular ultrasound (IVUS)-guided procedures were performed in 279 (54%) patients and angiographic guidance was used in the remainder. Minimal lumen diameter was significantly greater in CBA-BMS than BA-BMS (2.65±0.40 mm vs 2.52±0.4 mm, p<0.01) and % diameter stenosis (%DS)-post was less in CBA-BMS than BA-BMS (14.0±5.9% vs 16.3±6.8%, p<0.01). %DS-follow-up was subsequently less in CBA-BMS than BA-BMS (32.4±15.1% vs 35.4±15.3%, p<0.05) associated with lower rates of restenosis in CBA-BMS than BA-BMS (11.8% vs 19.6%, p<0.05) and less target lesion revascularization (TLR) in CBA-BMS than BA-BMS (9.6% vs 15.3%, p<0.05). Patients were divided into 4 groups based on the device used before stenting and IVUS use (IVUS-CBA-BMS: 137 patients; Angio-CBA-BMS: 123; IVUS-BA-BMS: 142; and Angio-BA-BMS: 119). At follow-up IVUS-CBA-BMS had a significantly lower restenosis rate (6.6%) than Angio-CBA-BMS (17.9%), IVUS-BA-BMS (19.8%) and Angio-BA-BMS (18.2%, p<0.05). Conclusions Restenosis and TLR were significantly lower in CBA-BMS than BA-BMS. This favorable outcome was achieved because of the lower restenosis rate conferred by the IVUS-guided-CBA-BMS strategy (6.6%). The restenosis rates obtained with this strategy were comparable to those achieved with DES. (Circ J 2007; 71: 1 - 8)

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Background The relationship between renal dysfunction and mortality in patients with myocardial infarction (MI) has been extensively investigated, but there are limited data about this relationship in patients presenting with non-ST-segment-elevation MI and unstable angina. Therefore, the aim of the present study was to investigate whether renal insufficiency is an independent predictor for in-hospital mortality among such patients. Methods and Results Two thousand a hundred and seventy-two patients presenting with acute coronary syndrome (ACS) in 6 Greek hospitals were enrolled. Creatinine clearance rates were estimated by the Cockcroft-Gault formula. Five percentage of patients presented with severe renal dysfunction, 27% with moderate dysfunction and the other 68% were normal. Patients with moderate or severe renal dysfunction were older, more likely to be women and more likely to have history of hypertension and diabetes mellitus compared with those with normal renal function. In comparison with patients with normal renal function, those with moderate and severe renal dysfunction were respectively 3- and 12-fold more likely to die. Moreover, moderate and severe renal insufficiency continued to be a prognostic factor for mortality, even after controlling for potential confounders. Conclusions Creatinine clearance rate is an important independent predictor of in-hospital mortality, so patients with ACS complicated by renal dysfunction should receive more aggressive medical care. (Circ J 2007; 71: 9 - 14)

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Background The sirolimus-eluting stent (SES) is currently the sole drug-coated stent approved for use in Japan, but there are few reports on its safety and outcomes in Japan. Methods and Results From May 2004 to February 2005, a total of 297 patients with 402 lesions were treated with SES at 6 hospitals in the Kansai district. Follow-up angiography was performed in 82% of the patients and 80% of the lesions at 182±35 days after stenting. Coronary stenosis was evaluated using quantitative coronary angiography. Clinical and angiographic data were analyzed. Minimum lesion diameter was 0.75±0.52 mm and the reference diameter was 2.81±0.47 mm before stenting. The SES successfully dilated 99.5% of the lesions with few major adverse cardiac events. Restenosis occurred in 4.0% and the target lesion revascularization rate was 3.7%. Restenosis correlated with chronic hemodialysis, calcification, occlusion, ostial lesions, lesions kinked >45 degrees, right coronary artery (RCA) lesions and lesions at the ostium of the RCA. Conclusion SES demonstrated a high rate of successful implantation with few complications, and mid-term outcomes were excellent. Patients with lesions at the ostium of the RCA or under chronic hemodialysis developed restenosis. (Circ J 2007; 71: 15 - 19)

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Background The degree to which abnormal glucose tolerance contributes to the development of coronary artery disease (CAD) has not been clarified in Japanese. The relationship between abnormal glucose tolerance and severity of coronary artery stenosis, as well as the contributions of hypertension, diabetes and other risk factors for CAD to recurrence of the disease, were investigated in the present study. Methods and Results The subjects were 474 consecutive patients (mean age: 63.8±11.3 years) with suspected CAD who were admitted to Sapporo Medical University Hospital during April 1, 1997 to March 31, 2004. The coronary index and stenosis score were higher in subjects with diabetes mellitus (DM) and in subjects with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) than in subjects with normal glucose tolerance (NGT). Ischemic episodes recurred during the observation period (mean 2.5 years) in 61 of 341 patients diagnosed as having CAD. In the follow-up subjects, systolic blood pressure (SBP) was significantly higher in the recurrence group than in the non-recurrence group, and SBP was a significant variable in logistic regression analysis after adjustment for age, gender, hemoglobin A1c, total cholesterol, body mass index, smoking history, family history and stenosis score. The relative risk of recurrence became 1.7-fold higher with a rise in SBP of 10 mmHg (95% confidence interval: 1.252-2.250). Analysis of the relationship between glucose tolerance and recurrence showed that the rate of recurrence was higher in patients with IFG + IGT + DM than in those with NGT. Conclusions CAD progresses not only in patients with DM but also in those with IGT. The rate of recurrence of ischemic episodes increases in individuals with IGT or DM, and suggesting that hypertension is a risk factor for recurrence of ischemic episodes. Management of glucose tolerance and blood pressure is therefore important for prevention of CAD in Japanese. (Circ J 2007; 71: 20 - 25)

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Background In recent years some studies have shown that metabolic syndrome (MS) is associated with inflammation, indicated by high-sensitivity C-reactive protein (hsCRP), but there have been few population-based studies, especially in Japan. Methods and Results The study subjects were 2,191 men and women examined between 1992 and 1995 with the necessary data to ascertain MS as part of the Jichi Medical School Cohort Study. CRP was measured by nephelometry. There were 109 subjects defined as having MS (5.0%), and the proportion of MS cases was higher in men (9.4%) than in women (1.8%). Geometric mean and median CRP in the MS group was higher than that in the non-MS (geometric mean; p<0.001, median: 0.312 mg/L in MS and 0.122 mg/L). Proportion of MS increased with CRP, after the subjects were divided by tertile of CRP (odds ratio, 95% confidence interval 1^st tertile as a reference; 2^nd tertile: 2.9, 1.5-5.9, 3^rd tertile: 5.7, 3.1-11.1). Conclusion Inflammation, measured by the concentration of hsCRP, was elevated in cases of MS in the general Japanese population. Longitudinal data should be examined in the future. (Circ J 2007; 71: 26 - 31)

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Background Many angiotensin II type 1 receptor blockers (ARBs) are available for clinical use, but because they do not all have the same effects, the present study investigated whether all benefits conferred by ARBs are class effects. Methods and Results Study 1 was a case - control study of patients with coronary artery disease, which showed that a non-depressor dose of valsartan significantly decreased the rate of target lesion revascularization at 6 months after stenting compared with the control group without ARB treatment. In Study 2, 44 patients with acute myocardial infarction who randomly received an initial lower dose of either valsartan or losartan after stenting were evaluated. The late loss and decrease in %diameter stenosis in the valsartan group were significantly lower than those in the losartan group as assessed by quantitative coronary angiography after 6 months. In addition, the valsartan group showed a significantly lower expression of intracellular adhesion molecule-1 and L-selectin. Conclusion A non-depressor dose of ARB may have beneficial effects on coronary restenosis that are associated with the regulation of adhesion molecules, and these effects might not be a class effect of ARBs. (Circ J 2007; 71: 32 - 38)

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Background There has not been a longitudinal investigation of the influence of angiotensin-converting enzyme (ACE) insertion/deletion and angiotensinogen (AGT) M235T gene polymorphisms on repolarization parameters, such as QT dispersion (QTd) and the peak and the end of the T-wave interval (Tpe). Methods and Results Electrocardiographys were recorded from 106 elderly Chinese at baseline, and 2^nd and 4^th year follow-up. The corrected QT (QTc), QTd, QTc dispersion (QTcd) and Tpe were manually calculated. Average age was 72.7±4.1 years (range 62-81). QTd, QTcd and Tpe were significantly prolonged (all p<0.001 at the 2^nd and 4^th year). At the 4^th year the magnitude of the QTd prolongation, but not Tpe, was significantly higher in subjects carrying the ACE D allele than non-D-allele carriers (p=0.001), as was QTcd (p=0.002). This association was still significant in the multivariate analyses (p<0.001 and p=0.001 for QTc and QTcd, respectively). No significant correlation was found between repolarization parameters and AGT genotype. Conclusions This longitudinal study shows that the ageing process is associated with prolongation of QTd, QTcd and Tpe after 4 years follow-up. The elderly Chinese subjects with the ACE D-allele had greater prolongation QTd and QTcd. (Circ J 2007; 71: 39 - 45)

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Background It has been previously reported that the efficacy of class I antiarrhythmics in preventing the recurrence of symptomatic paroxysmal and persistent atrial fibrillation (AF) is limited when AF lasts for 48 h or more. However, it is unclear whether the efficacy of amiodarone, a class III drug, is superior to class I antiarrhythmics in patients with long-lasting AF. Method and Results The relationship between the duration of tachycardia and the efficacy of amiodarone in preventing recurrence of tachycardia was examined in 55 patients (37 men, 18 women, mean age 68±9 years) to whom amiodarone was administered after electrical or pharmacological cardioversion for paroxysmal and persistent AF. In 26 patients, paroxysmal and persistent AF ceased within 48 h after onset (Group A), and in the other 29 patients, it ceased after 48 h (Group B). Patient characteristics and actuarial recurrence-free rates were compared between the 2 groups. The mean follow-up period was 30±11 months. No statistically significant difference between the groups was found in patient characteristics. Actuarial recurrence-free rates in Group A and B at 1, 3, 6, 9, and 12 months were 100%, 81%, 69%, 62%, and 54%, and 93%, 79%, 66%, 52%, and 48%, respectively (p= NS at 12 months). The period of maintenance of sinus rhythm was 14.7±3.2 months in group A and 13.3±3.3 months in group B (mean ± SE, p= NS). Conclusion In the case of amiodarone, efficacy for maintaining sinus rhythm after cardioversion of AF was not biased by the duration of arrhythmia. This observation suggests amiodarone is effective in maintaining normal sinus rhythm after cardioversion, even in patients with long-lasting AF and electrical atrial remodeling. (Circ J 2007; 71: 46 - 51)

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Background Patients with atrial fibrillation (AF) are at risk for thromboembolism, and coexistent cardiovascular diseases could affect their prothrombotic profiles. The relationship between plasma hemostatic markers and aortic atherosclerosis was determined in patients with AF or in sinus rhythm (SR). Methods and Results Sixty patients with nonrheumatic AF and 46 patients in SR who underwent transesophageal echocardiography and did not receive anticoagulant therapy constituted the study group. Markers for platelet activity (platelet factor 4 and β-thromboglobulin), thrombotic status (thrombin-antithrombin III complex and prothrombin fragment 1+2 (F1+2)) and fibrinolytic status (plasmin-α2-plasmin inhibitor complex (PIC) and D-dimer) were determined. Levels of F1+2, PIC and D-dimer were higher in AF patients with severe atheroma than in those without severe atheroma (p<0.05). In patients in SR, hemostatic markers were not significantly increased even if they had severe aortic atherosclerosis. AF (Odds ratio (OR) 4.06, p=0.04) and age ≥75 years (OR 3.98, p=0.02) were independently predictive of elevated D-dimer levels and severe atheroma was predictive of elevated F1+2 levels (OR 5.52, p=0.04). Conclusions Elderly patients with AF and severe aortic atherosclerosis might be in a prothrombotic state, and could benefit from intensive antithrombotic therapy. (Circ J 2007; 71: 52 - 56)

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Background The response of the ST-segment in the right precordial leads to Na⁺ channel blockers in patients without structural heart disease and a typical Brugada-type ECG has not been fully elucidated. Methods and Results A pilsicainide challenge test was performed in 161 patients and according to recently established ECG criteria and an organized computer algorithm, the ST morphology was classified and the maximum increase in the J wave amplitude (maxΔJ) from the standard and high right precordial leads V_1-3 was examined. Before the test, subjects exhibiting type 1 ECG in the standard leads were excluded. After administering pilsicainide, type 1 ECGs in the standard leads were observed in 31 cases and a maxΔJ of ≥200 μV was observed in 29 cases (23 type 1, 2 type 2/3 and 4 normal ECGs). In the additional higher right precordial leads, type 1 ECGs were observed in 55 cases and a maxΔJ of ≥200 μV was observed in 45 cases (42 type 1 and 3 type 2/3 ECGs). Conclusions A maxΔJ ≥200 μV induced by pilsicainide, including that measured in the high right precordial leads, was associated with a change mainly to a type 1 ECG. (Circ J 2007; 71: 57 - 62)

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Background The characteristic features of QRST integral mapping in the Brugada-type resting ECG of patients at a high risk for life-threatening ventricular arrhythmias were examined. Methods and Results QRST integral mapping was performed in 11 Brugada-type ECG patients with histories of aborted sudden death, spontaneous ventricular tachycardia and fibrillation (VT/VF) or programmed electric stimulation-inducible VT/VF (high risk group); 13 Brugada-type ECG patients without a history of such events (low risk group); and 21 age-matched healthy controls. Individual QRST isointegral maps revealed the minimum integral in the mid-to-right upper chest in 100% and 85% of the control and low risk groups, respectively, whereas this integral was 64% in the upper right back of the high risk group (p<0.05). On the QRST integral departure maps, the abnormal positive departure area (integral value ≥+2 standard deviation) was located in the mid-to-right upper chest in 82% and 8% of the high and low risk groups, respectively (p<0.05). During the follow-up period, sudden death or VF occurred in 4 of 6 high risk patients with both the abnormal findings. Conclusion The abnormal positive departure area in the mid-to-right upper chest and the minimum QRST integral in the right upper back were distinct hallmarks for screening patients with the high risk Brugada-type ECG. (Circ J 2007; 71: 63 - 69)

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Background A histopathological assessment of left atrial appendages (LAA) resected during surgical treatment for atrial fibrillation (AF) was made, with the aim of improving the prediction of postoperative AF recurrence. Methods and Results This clinicopathological study involved 57 surgical cases of valvular AF and 34 age- and sex-matched control autopsy cases with a history of sinus rhythm. LAA from the cases with valvular AF showed greater hypertrophy of cardiomyocytes (p<0.0001), greater nuclear enlargement (p<0.0001), more bizarre nuclei (BN; p<0.0001), and more intercellular fibrosis (ICF; p<0.001). Partial disarray of cardiomyocytes and fatty infiltration were recognized in both the AF and control groups. Thirty-seven cases had maintained sinus rhythm after surgery from 7 months to 10 years. AF recurred within a month of surgery in 17 and after a month in 3; there was no significant difference in histopathological features between them. These 20 cases had more cellular hypertrophy (p<0.025), nuclear enlargement (p<0.025), BN (p<0.01), and ICF (p<0.025) than those who maintained sinus rhythm after surgery. Conclusions The histopathological findings for LAA reflected the underlying valvular diseases; however, the most reliable predictors of postoperative AF recurrence were hypertrophy of cardiomyocytes, bizarre shaped nuclei, and extensive ICF. (Circ J 2007; 71: 70 - 78)

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Background The aim of this study was to evaluate the relationship between the preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and the need for the inotropic support in the early postoperative period of patients undergoing coronary artery bypass graft surgery. Methods and Results The patients were divided into 2 groups: NT-proBNP level <220 pg/ml (group A, n=26) or >220 pg/ml (group B, n=26). The normal value for NT-proBNP level was accepted as <220 pg/ml. The cardiac output was measured on arrival in intensive care and at the 16^th hour. The groups were compared with respect to early postoperative hemodynamic measurements, urinary output, use of inotropic agents and requirement for additional cardiac-assist devices. Left ventricular ejection fraction, cardiac output and cardiac index were lower in group B and inotropic agents were used for a longer period of time and at higher doses in this group (p<0.05). Conclusion Measurement of the NT-proBNP level in the period before cardiac surgery can indicate the postoperative prognosis of the patient and may be a predictor of the need for postoperative inotropic treatment. (Circ J 2007; 71: 79 - 83)

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Background Dilatation of the ascending aorta in aortic stenosis may be partly explained by intrinsic wall structure changes, but the relative contribution of altered hemodynamics is unclear. The aim of this study was to assess the association between ascending aortic dimensions and valve stenosis severity. Methods and Results An analysis of echocardiographic examinations was conducted in 296 patients with aortic stenosis (179 males, mean age 71 years), 57 with bicuspid and 239 with tricuspid aortic valve, mean transaortic gradient 43±20 mmHg, and not more than moderate aortic regurgitation. Aortic dimensions at the level of annulus, sinuses of Valsalva, sinotubular junction and proximal ascending aorta were measured. Only height (p<0.001), degree of aortic regurgitation (p<0.01) and presence of bicuspid aortic valve (p<0.001) were independent predictors of ascending aortic dimensions. Conclusions An independent association between aortic pressure gradients and proximal ascending aortic dimensions was not observed in patients with bicuspid or tricuspid aortic valve stenosis. Therefore, the poststenotic dilatation of the ascending aorta is not explained by aortic stenosis severity itself. Possible nonhemodynamic causes deserve detailed study at the time of diagnosis. (Circ J 2007; 71: 84 - 88)

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Background The brachial - ankle pulse wave velocity (baPWV) is used to evaluate the degree of atherosclerosis and arterial distensibility, but its major limitation is that it is affected by changes in blood pressure (BP) during measurement. Recently, a new atherosclerotic index, the cardio-ankle vascular index (CAVI), has been developed by measuring PWV and BP. CAVI is adjusted for BP based on the stiffness parameter β and should measure arterial stiffness independent of BP. The purpose of this study was to evaluate the validity of CAVI compared with baPWV, the reproducibility of the measurement of CAVI, and the effect of BP changes on CAVI and baPWV. Methods and Results One thousand and thirty-three consecutive subjects undergoing health checkups were studied. CAVI was automatically calculated from the pulse volume record, BP, and the vascular length from heart to ankle. In this general population, both baPWV and CAVI demonstrated a positive correlation with age and systolic BP (SBP). CAVI showed a weaker correlation with SBP than baPWV. The measurement of CAVI demonstrated good reproducibility and was not affected by the increase in BP during measurement. Conclusions CAVI is a useful index of arterial distensibility and is not influenced by BP changes during measurement. (Circ J 2007; 71: 89 - 94)

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Background Peripheral arterial disease (PAD) is an important manifestation of systemic atherosclerosis and is associated with elevated cardiovascular morbidity and mortality. The aim of the present study was to evaluate the use of antiplatelet agents, statins and angiotensin-converting enzyme inhibitors (ACEI) in Chinese high-risk cardiovascular (CV) patients with PAD, with an emphasis on the need for aggressive medical management of all atherosclerotic manifestations. Methods and Results Medical records from 5,263 Chinese patients at high risk of CV were evaluated for the use of antiplatelet agents, statins and ACEI in patients with and without PAD. PAD was defined as an ankle - brachial index (ABI) <0.9 in either leg. Multivariable logistic regression analyses were performed to compare medication use in the 2 groups. A total of 5,254 patients were analyzed (52.9% male, mean age 67.3 years). The prevalence of PAD in the total patient group was 25.4%; 22.5% of them had PAD only. Overall, 5.7% had PAD only, 19.6% had PAD and coronary heart disease (CHD) or stroke or diabetes, 7.7% had CHD only, 12.6% had stroke only, and 13.6% had diabetes only. The 28.9% subjects having none of PAD, CHD, stroke or diabetes were used as the reference group. Only 65%, 37% and 47% of all patients received antiplatelet agents, statins and ACEI, respectively. Antiplatelets, statins, ACEI and all 3 medications were used less frequently in PAD only patients (58.1%, 35.9, 53.5% and 21.6%) vs CHD only (90.9%, 74.5%, 70.6% and 55.9%, p<0.001). All 3 proven efficacious therapies were prescribed for only 56% of patients with CHD only, 8% with stroke only, 13% with diabetes only and 21% with PAD only. Conclusion PAD is prevalent in Chinese high-risk CV patients, equivalent to CHD, but these patients receive less intensive treatment than those with CHD. Programs to improve CV risk reduction in these high-risk patients are needed. (Circ J 2007; 71: 95 - 99)

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Background Oxidative stress plays a role in the development of chronic peripheral arterial disease (PAD) because under these conditions redox regulation is impaired, inducing the S-glutathionylation of proteins. A method of estimating the levels of S-glutathionylated proteins has been developed using biotinylated glutathione S-transferase, which allows the study of their crucial role in the oxidative stress-related progression of PAD. Methods and Results The serum levels of S-glutathionylated proteins were examined in 41 patients with arteriosclerosis obliterans (ASO) and 38 age-matched non-ASO patients using biotinylated glutathione S-transferase. The levels were higher in the patients with ASO, even early on, and positively correlated with the ankle/brachial index. In vitro, the levels of S-glutathionylated proteins were reduced in the presence of glutathione and glutaredoxin. Conclusions Serum levels of S-glutathionylated proteins are a sensitive risk-marker for ASO at an early stage. (Circ J 2007; 71: 100 - 105)

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Backgound Cilostazol, a phosphodiesterase inhibitor, is an antiplatelet agent with positive chronotropic effect, the impact of which on left ventricular (LV) volume and function in acute myocardial infarction (AMI) was evaluated in the present study. Methods and Results In 56 patients with AMI treated with primary coronary stenting, serial echocardiographic studies within 24 h and at 6 months were performed. Patients received a conventional antiplatelet regimen either without cilostazol (group 1, n=29) or with cilostazol (group 2, n=27). At 6 months, the difference in the change in heart rate between group 1 and group 2 was statistically significant (9.9 beats/min; p=0.04). However, changes in LV end-systolic volume (LVESV) (7.1±8.2 vs 10.0±21.7 ml, p=0.60), LV ejection fraction (EF) (8.2±9.9 vs 9.0±12.6%, p=0.85) and the ratio of early mitral inflow velocity to the mitral annular velocity (E/E') (0.6±3.7 vs -1.7±3.2) were not different between the 2 groups. Cardiac event rate was similar between the 2 groups. On multivariate regression analyses, cilostazol therapy had no significant influence on the changes in LVESV, LVEF or E/E'. Conclusions In this study, the addition of cilostazol on conventional drug therapy had no adverse influence on LV remodeling or LV function after AMI. (Circ J 2007; 71: 106 - 111)

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Background To optimize the image reconstruction phase of multidetector-row computed tomography (MDCT) coronary angiography according to the heart rate is crucial. Methods and Results Scan data were reconstructed for 10 different phases in 58 sequential patients who underwent 8-row cardiac MDCT. The obtained images were scored and compared in terms of motion artifacts and visibility of the vessels, and moreover, ECG record-based evaluations were added for clarification of the temporal relationships among these 10 phases. In the cases with lower heart rates (<65 beats/min), the best quality images were obtained when the end of the image reconstruction phase was positioned at the peak of the P wave. In some cases with higher heart rates (>65 beats/min), they were obtained in the late systolic period. Conclusion As the heart rate increased, the optimal image reconstruction phase changed from mid diastole to late systole. However, it is recommended to try to decrease the heart rate of patients before data acquisition. (Circ J 2007; 71: 112 - 121)

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Background Transesophageal echocardiography (TEE) is regarded as the method of choice for imaging left atrial appendage thrombi (LAAT). However, the interobserver variability among 2 independent echocardiographic laboratories in diagnosing LAAT by multiplane TEE has not yet been assessed. Methods and Results The videorecordings of 50 patients in atrial fibrillation (25 from each laboratory) were blindly reviewed by 1 experienced observer from each institution. LAAT were assessed as present, absent or questionable. Indications for TEE were: cardioversion (n=17), valve disease (n=13), endocarditis (n=12), or embolism (n=8). The prevalence of LAAT was 10% (observer 1) vs 12% (observer 2). A questionable LAAT was assessed in 6% vs 12% and a LAAT was excluded in 84% vs 76%, respectively. By head-to-head comparison, disagreement occurred in 11 cases (22%, kappa =0.5). Discrepant results were not related to the echocardiographic equipment. Problems occurred because of reverberation artifacts of the ridge between the left atrial appendage and left upper pulmonary vein (n=5), and in differentiating LAAT from spontaneous echocardiographic contrast (n=4) or an echogenic atrioventricular groove (n=1). The differentiation of pectinate muscles from LAAT was the reason for disagreement in only 1 case. Eliminating the category of questionable thrombi increased the kappa value to 0.65. In 5 patients undergoing cardiac surgery, both observers had agreed on the presence (n=1) or absence (n=4) of LAAT, and intraoperatively the results of TEE were confirmed. Conclusion Even with multiplane TEE, interobserver variability among 2 independent echocardiographic laboratories for diagnosing LAAT remains high because of problems in differentiating LAAT from spontaneous echocardiographic contrast and reverberation artifacts. (Circ J 2007; 71: 122 - 125)

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Background Cardiac resynchronization therapy (CRT) improves glucose metabolism in the septum of patients with heart failure, so in the present study the predictive value of combined fluorodeoxyglucose (FDG)-positron emission tomography (PET) and metoxy-isobutyl isonitrile (MIBI)-single photon emission computed tomography (SPECT) for the prognosis of patients undergoing CRT was investigated. Methods and Results Fourteen patients (70.3±8.2 years) who underwent FDG-PET and MIBI-SPECT before implantation of a biventricular pacemaker were enrolled. The total number of matches, mismatches, reverse mismatches, summed difference score (SDS: sum total of FDG - MIBI scores) and SDS per segment (%SDS) in each of 5 areas of myocardium (septum, anterior, lateral, inferior area, apex) was calculated and compared between the survival groups (all survival: survival group; survival without ischemic heart disease (IHD): non-IHD survival group) and non-survival group. Both the number of reverse mismatch segments and the %SDS in the septum in the non-IHD survival group were significantly greater than in the non-survival group (3.2±1.6 vs 0.5±0.6, p<0.05; 0.62±0.61 vs -0.11±0.19, p<0.05). The receiver-operating characteristics curves for prognosis showed that the area under the curve for the number of reverse mismatch segments in the septum (0.93; confidence interval 0.61-0.98) was significantly greater. Conclusion A reverse mismatch pattern in the septum can predict a good prognosis for patients treated with CRT. (Circ J 2007; 71: 126 - 131)

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Background The usefulness of sustained-release erythropoietin for improving left ventricular (LV) function without polycythemia was evaluated in a rat chronic myocardial infarction model. Methods and Results Four weeks after left coronary artery ligation, 50 Sprague-Dawley rats were assigned to 5 groups (n=10, each). Control group had a gelatin sheet (20×20 mm) containing saline applied to the infarct area, whereas the 4 treatment groups had gelatin sheets incorporating erythropoietin 0.1 U, 1 U, 10 U and 100 U, respectively. Endpoint measurements performed at 8 weeks after the coronary ligation revealed that the fractional area change was larger for erythropoietin 1 U and 10 U than in the other 3 groups. The LV end-systolic elastance and the time constant of isovolumic relaxation were better for erythropoietin 1 U and 10 U than in the other 3 groups. The density of vessels larger than 50 μm in diameter was the highest in the erythropoietin 1 U group. The number of red blood cells was significantly increased in groups receiving erythropoietin 10 U and 100 U. Conclusions Gelatin hydrogel sheets incorporating 1 U erythropoietin improved LV function without inducing polycythemia in a rat chronic myocardial infarction model. (Circ J 2007; 71: 132 - 137)

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Background Regeneration of the lung microvasculature and replacing pulmonary artery lesions with functional endothelial cells could be a novel and effective therapeutic strategy for treating advanced pulmonary arterial hypertension (PAH). In the present study it was postulated that granulocyte colony-stimulating factor (G-CFS), which induces the proliferation of endothelial cells, would stimulate endothelial regeneration in situ at sites of impaired lung vasculature and prevent the development of PAH. Methods and Results Daily administration of G-CSF for 48 days did not affect the hemodynamism of normal Fischer 344 rats. PAH was induced with monocrotaline (60 mg/kg) and G-CSF was administered daily (100 μg/kg per day). Echocardiographic findings and an invasive catheter study indicated a significant decrease in the progression of PAH in rats given G-CSF. Furthermore, G-CSF increased Ki-67 positivity in the pulmonary arteries of PAH rats but did not accelerate c-kit positive cell recruitment into peripheral blood. Daily doses of G-CSF at both 2 and 100 μg/kg improved the survival and body weight gain of PAH rats. Conclusions G-CSF improved the progression of PAH in a rat model, possibly by stimulating pulmonary endothelial cells to proliferate at sites of impaired lung vasculature. These findings show that cytokine therapy for PAH is valid based on the concept of vascular regeneration. (Circ J 2007; 71: 138 - 143)

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Background Controversy exists regarding the effects of statin therapy on progressive insulin resistance (IR) and its consequences, in the present study a rat model of spontaneously developing type II diabetes mellitus (DM) was used to examine the impact of atorvastatin (AS) vs pravastatin (PS). Methods and Results The Otsuka Long-Evans Tokushima Fatty rats were either untreated or treated with 100 mg/kg per day of AS or PS from 6 weeks of age for 24 weeks. AS achieved much greater lipid lowering than PS. Serial oral glucose tolerance tests revealed new-onset diabetes was delayed by PS only. The untreated rats exhibited a progressive decrease in plasma adiponectin, increases in plasma leptin and tumor necrosis factor-α, and reduction of plasma nitric oxide (NO), which were limited more by PS than AS. PS, but not AS, enhanced adiponectin mRNA expression in white adipose tissue at 30 weeks. Cardiac endothelial NO synthase expression was upregulated, and overexpression of both transforming growth factor-β1 and monocyte chemoattractant protein-1 mRNA was limited more by PS than AS. Coronary perivascular fibrosis at 30 weeks was suppressed only by PS, which was accompanied by preserved left ventricular diastolic function assessed with Doppler echocardiography. Conclusions The moderate lipid lowering by PS, but not the intensive lipid lowering by AS, prevented new-onset DM and diastolic dysfunction in a rat model of IR, and this was associated with preferable adipocytokine profiles and cardiac redox states. (Circ J 2007; 71: 144 - 152)

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Background Cold static storage (CS) is a proven preservation method for heart transplantion, yet early postoperative graft dysfunction remains prevalent, so continuous perfusion (CP) during ex vivo transport may improve viability and function of heart grafts. Methods and Results Canine hearts underwent CP (n=9) or CS (n=9) for 6 h while intramyocardial pH was continuously monitored. Biopsies were assayed for ATP, caspase-3, malondialdehyde (MDA), and endothelin-1 (ET-1) levels at baseline, after preservation (t₁), and after 1 h of blood reperfusion on a Langendorff model (t₂). Functional recovery was determined at t₂ by +dP/dt, -dP/dt, developed pressure, peak pressure and end-diastolic pressure. CP resulted in higher tissue pH and ATP stores and reduced caspase-3, MDA and ET-1 levels compared with CS at both t₁ and t ₂. Post reperfusion recovery was significantly greater in CP vs CS for all myocardial functional parameters except end-diastolic pressure. Weight gain was significantly increased in CP vs CS at t ₁, but not at t₂. Conclusions Low-grade tissue acidosis and energy depletion occur during CS and are associated with oxidative injury and apoptosis during reperfusion. CP attenuates these biochemical and pathologic manifestations of tissue injury, together with improved myocardial recovery, despite mild, transient edema. (Circ J 2007; 71: 153 - 159)

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Radiofrequency catheter ablation was performed in 2 patients with atrial tachycardia (AT). In both cases the AT originated from the inferoseptal portion of the right atrium, and the cycle length was 210 ms. The surface ECG demonstrated common counterclockwise atrial flutter, probably caused by functional block in the clockwise direction at the cavo-tricuspid isthmus and posterior right atrium with rapid activation of the origin. Although rare (2%), AT originating from the inferoseptum of the right atrium should be considered when the surface ECG exhibits common atrial flutter. (Circ J 2007; 71: 160 - 165)

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A 45-year-old man without major coronary risk factors, including hypertension, diabetes mellitus, smoking, hypercholesterolemia, hyperuricemia, or a family history of early cardiovascular disease, presented with acute coronary syndrome. Angiography showed thrombus formation in segment 7 of the left anterior descending coronary artery, and percutaneous coronary intervention was successful after implantation of a bare metal stent. Scintigraphy showed the absence of ¹²³I-β-methyl-iodophenyl pentadecanoic acid accumulation in the myocardium. Flow cytometric analysis of platelets and monocytes showed the absence of cluster differentiation (CD)-36 expression. These findings are consistent with a diagnosis of CD36 deficiency type 1, which might be associated with cardiovascular disease. The patient had no apparent major coronary risk factors except for insulin resistance and an abnormal lipoprotein profile. The findings suggest that in this case the CD36 deficiency type 1 was the pathogenic mechanism of acute coronary syndrome relative to insulin resistance and modification of the lipid profile. (Circ J 2007; 71: 166 - 169)

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Wrong:Pertussis toxin (PTX3)
Right:Pentraxin 3 (PTX3)

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