Background The effects of nasal oxygen (O₂) supply at night using conventional home oxygen therapy (HOT) equipment on quality of life (QOL) and sleep-disordered breathing (SDB) were evaluated in patients with congestive heart failure (CHF). Nasal nocturnal O₂ therapy not only stabilizes SDB but also reduces sympathetic activity, and improves exercise capacity in patients with CHF. However, the effects of oxygen on the cardiac function and QOL of heart failure patients have not been fully elucidated. Methods and Results Fifty-six patients with CHF (New York Heart Association class II - III, left ventricular ejection fraction (LVEF) ≤45%) and central sleep apnea (CSA) with Cheyne-Stokes respiration (CSR) were randomly assigned to receive either nocturnal O₂ (HOT group, n=25) or usual breathing (control group, n=31) for 12 weeks. Respiration, airflow and arterial oxygen levels were monitored with determination of apnea/hypopnea index (AHI) and oxygen desaturation index (ODI) during sleep. LV function was determined by radionuclide angiography or echocardiography. QOL was assessed by the Specific Activity Scale questionnaire. In the HOT group, nocturnal O₂ resulted in significant improvements in AHI (21.0±10.8 to 10.0±11.6 events/h, mean ± SD, p<0.001), ODI (19.5±9.8 to 5.9±8.7 dips/h, p<0.001) and Specific Activity scale (4.0±1.2 to 5.0±1.5 Mets, p<0.001). LVEF also increased from baseline to the end of the study (34.7±10.4 to 38.2±13.6%, p=0.022). Conclusions In patients with stable CHF and CSR, HOT at night improves SDB, LV function and QOL, and thus is a valuable nonpharmacological option for the treatment of patients with CHF and CSR-CSA. (Circ J 2006; 70: 1 - 7)

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Background Cigarette smoking is one of the major risk factors for atherosclerotic coronary disease, but the precise mechanism(s) by which cigarette smoking promotes atherosclerosis remains unknown. As there is now increasing evidence that atherosclerosis is an inflammatory condition, the present study investigated whether inflammation exists in smokers. Methods and Results The inflammatory markers and lipid profiles were compared among a current-smoker group (210 patients, mean age 61.8±11.0 years), past-smoker group (115 patients, 67.1±9.0 years) and never-smoked group (113 patients, 68.2±10.7 years), all of whom had no apparent signs of inflammation. The respective levels of blood leukocytes, platelets, C-reactive protein and fibrinogen were significantly higher in current-smokers than in the never-smoked group (6,600±1,723 /μl vs 5,638 ±1,313 /μl p<0.01; 22.7±6.8 ×10⁴ /μl vs 18.7 ±7.4×10⁴ /μl, p<0.01; 3.50±4.91 mg/L vs 1.92±3.02 mg/L, p<0.01; 334.2±90.9 mg/dl vs 314.7±80.2 mg/dl, p<0.05). The respective levels of plasma triglycerides, remnant-like particle cholesterol and apolipoprotein-B were significantly higher and that of high-density lipoprotein cholesterol significantly lower in the current-smokers than in the never-smoked group (152.4±96.2 mg/dl vs 120.5±58.1 mg/dl, p<0.01; 5.4±6.3 mg/dl vs 3.8±2.0 mg/dl, p<0.05; 101.6±23.7 mg/dl vs 95.0±21.2 mg/dl, p<0.05; 45.2±12.3 mg/dl vs 50.6±15.6 mg/dl, p<0.01). Past smokers had intermediate values between those of current-smokers and never-smoked. Conclusions Low-grade inflammation, atherogenic dyslipidemia, and hypercoagulability are present in smokers compared with those who have never smoked among subjects without apparent inflammation who underwent coronary angiography on suspicion of coronary artery disease. (Circ J 2006; 70: 8 - 13)

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Background In familial hypercholesterolemia (FH), low-density lipoprotein-cholesterol (LDL-C)-lowering therapy is important to avoid predisposition to coronary artery disease. This study investigated the advantages of combined therapy with atorvastatin and colestimide vs intensive monotherapy with atorvastatin. Methods and Results The trial used a randomized cross-over design consisting of 2 16-week periods of open-label drug therapy. Among the 24 initial patients, 17 heterozygous FH patients (age: 54.1 years; 5 males) were enrolled after 20 mg/day atorvastatin failed to achieve their target level. The patients received 20 mg/day atorvastatin and 3 g/day colestimide or 40 mg/day atorvastatin. Fifteen patients completed the trial and their LDL-C reduced from 5.07±1.10 mmol/L to 3.76±0.90 mmol/L with the combined therapy and to 3.81±0.50 mmol/L with the intensive monotherapy. Although the 2 therapies showed comparable mean effects for decreasing LDL-C, similar adverse reaction and cost, each therapy was predominantly more effective in some patients than in others. The triglyceride and high-density lipoprotein cholesterol levels were similar in both therapies. Conclusions To achieve the therapeutic target of LDL-C level for refractory FH, the LDL-C-lowering therapy selected can be either intensive monotherapy or combined therapy as the next to standard statin therapy. (Circ J 2006; 70: 14 - 20)

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Background Early defibrillation of ventricular tachycardia and fibrillation (VT/VF) is an urgent and most important method of resuscitation for survival in cardiopulmonary arrest (CPA). We have previously reported that nifekalant (NIF), a specific I_Kr blocker developed in Japan, is effective for lidocaine (LID) resistant VT/VF in out-of-hospital CPA (OHCPA). However, little is known about the differences in the effect of NIF on OHCPA with acidosis and in-hospital CPA (IHCPA) without acidosis. Methods and Results The present study enrolled 91 cases of DC shock resistant VT/VF among 892 cases of CPA that occurred between June 2000 and May 2003. NIF was used (0.15-0.3 mg/kg) after LID according to the cardiopulmonary resuscitation (CPR) algorithm of Tokai University. The defibrillation rate was higher in the NIF group for both OHCPA and IHCPA than for LID alone, and the VT/VF rate reduction effect could be maintained even with acidosis. However, sinus bradycardia in OHCPA, and torsades de pointes in IHCPA were occasionally observed. These differences in adverse effects might be related to the amount of epinephrine, serum potassium levels, serum pH, and interaction with LID. Conclusions NIF had a favorable defibrillating effect in both CPA groups, and it shows promise of becoming a first-line drug for CPR. (Circ J 2006; 70: 21 - 27)

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Background Coils are the only devices available for transcatheter occlusion of patent ductus arteriosus (PDA) in Japan. Since April 1999, we have introduced a 0.052-inch Gianturco coil (0.052-inch coil) to close PDA ≥2.5 mm. Methods and Results A retrospective survey of the outcome of coil occlusions for PDA ≥2.5 mm before and after the 0.052-inch coil became available found that (1) the frequency of PDA ≥2.5 mm among all candidates for coil occlusion significantly increased after the availability of a 0.052-inch coil (p<0.01); (2) deployment complicated by migration (p<0.01), and prolonged procedure time (p<0.05) were significantly decreased after the introduction of the 0.052-inch coil. In a multivariate logistic regression model for uneventful deployment adjusted for age, pulmonary to systemic flow ratio, and use of a 0.052-inch coil, use of the 0.052-inch coil significantly decreased eventful deployment (p<0.05); and (3) successful deployment of a coil for PDA ≥4 mm significantly increased with the 0.052-inch coil (p<0.01). Complete occlusion was achieved once deployment was successful. Conclusion Introduction of the 0.052-inch coil decreased complicated coil occlusion deployment for PDA ≥2.5 mm, and contributed to a better likelihood of coil occlusion for PDA ≥4 mm. (Circ J 2006; 70: 28 - 30)

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Background The relationship between platelet activity and myocardial injury in patients with ST-segment elevated (ST-se) acute myocardial infarction (AMI) remains unclear. This study tested the hypothesis that platelet activity (expressed by CD62p) is enhanced and predictive of both the extent of myocardial damage and 30-day clinical outcome in patients with ST-se AMI undergoing primary coronary stenting. Methods and Results Platelet CD62p expression prior to coronary angiographic was prospectively measured using flow cytometry in 45 consecutive patients with AMI undergoing primary coronary stenting. The CD62p expression was also evaluated in 20 healthy and 20 at-risk control subjects. The CD62p expression was significantly higher in AMI patients than in healthy and at-risk control subjects (all p values <0.0001). Patients with high CD62p expression (≥8%) had significantly higher creatine kinase-MB (p<0.0001) levels, higher incidence of cardiogenic shock (p=0.009) upon presentation, significantly lower left ventricular ejection fraction (p=0.0003), and significantly higher incidence of 30-day composite major adverse clinical outcomes (MACO) (advanced congestive heart failure ≥class 3 or 30-day mortality) (p<0.0001) than those patients with low CD62p expression (<8%). Multiple stepwise logistic regression analysis demonstrated that only high CD62p expression (≥8%) was an independent predictor of 30-day MACO (all p<0.0001). Conclusions Platelet activation was significantly increased in patients with ST-se AMI. Initial CD62p expression was independently associated with extent of myocardial damage and 30-day MACO. (Circ J 2006; 70: 31 - 36)

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Background The effects of intraaortic balloon pumping (IABP) are considered to be a reduction in myocardial oxygen demand because of systolic left ventricular unloading and an increase in coronary blood flow. Although the former effect has been consistently recognized, the latter effect remains controversial. The purpose of this study was to examine the effects of IABP on the angiographic no-reflow phenomenon. Methods and Results The coronary flow velocity pattern of the left anterior descending artery (LAD) was assessed by transthoracic Doppler echocardiography during IABP counterpulsation, and the effects of IABP were compared between angiographic no-reflow and good reflow patients. The study group comprised 17 patients with anterior myocardial infarction who underwent percutaneous coronary intervention and IABP for typical clinical indications. Echocardiographic data were obtained during 2:1 balloon pumping after coronary angioplasty. In the good reflow group (n=9), IABP counterpulsation increased the mean diastolic flow velocity (MDFV) and peak diastolic flow velocity (PDFV) by 56±32% (p<0.001) and 48±27% (p<0.001), respectively. In contrast, in the no-reflow group (n=8), IABP only increased the MDFV and PDFV by 19±33% (p=0.24) and 6±12% (p=0.22), respectively. Diastolic deceleration time was smaller and the prevalence of systolic retrograde flow was greater in the no-reflow group than in the good reflow group, and IABP affected neither parameter. Conclusions IABP had limited effects on LAD flow velocity pattern in patients with the angiographic no-reflow phenomenon. (Circ J 2006; 70: 37 - 43)

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Background Radiation skin injuries have been reported as a result of various procedures, so in the present study the patients' entrance skin dose (ESD) during percutaneous coronary intervention (PCI) was evaluated. Methods and Results ESDs were assessed during 97 procedures (13 for chronic total occlusion (CTO), 14 for multivessel stenoses, 22 for single-vessel multiple stenoses, and 48 for single stenosis). The patients wore jackets that had 48 or 52 radiosensitive indicators placed on the back during the PCI procedures, with 8 other indicators placed on both upper arms. After the procedure, the color of the indicators was analyzed with a color measuring instrument, and the patients' ESDs were calculated from the color difference of the indicators. The average maximum ESDs of the patients were 4.5±2.8 Gy (median: 4.6 Gy) for CTO, 2.3±0.7 Gy (median: 2.4 Gy) for multivessel stenoses, 1.8±1.0 Gy (median: 1.5 Gy) for single-vessel multiple stenoses, and 1.4±0.9 Gy (median: 1.2 Gy) for single stenosis. Conclusions Skin injury can occur during PCI, especially for CTO, so it is important to estimate each patient's ESD and attempt to reduce it. (Circ J 2006; 70: 44 - 48)

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Background Vasodilator response to acetylcholine (ACh) (ie, endothelium-dependent dilation) is impaired in the peripheral and coronary circulation of patients with coronary risk factors and coronary artery disease (CAD). There is a close relationship of vasodilator response to ACh in both the coronary artery (CA) and the brachial artery (BA), but the comparative prognostic importance of these responses has not been fully investigated in relatively low-risk suspected CAD. Methods and Results The flow responses of both the CA and BA were measured in 70 patients with suspected CAD, excluding patients with triple-vessel disease and known peripheral or cerebrovascular disorders. A Doppler guidewire was placed into a major branch of the CA and a proximal portion of the left BA. ACh was infused at 10^-8, 10^-7 and 10^-6 mol/L for 3 min into the CA and at 7.5, 15, and 30 μg/min for 5 min into BA. The flow response was obtained by multiplying the average peak velocity by the cross-sectional area from quantitative angiography. Vasodilator response to ACh was assessed by the ratio of ACh-induced flow/baseline flow, expressed as coronary blood flow index (CBFI) or brachial blood flow index (BBFI). There were 39 CAD patients (61±8 years old) and 31 normal coronary patients (NL, 58±11 years old) who were followed up for 53±17 months. Eleven patients had coronary events (CE) during this period: 1 case of nonfatal myocardial infarction and 10 cases of unstable angina. A strong correlation between CBFI and BBFI was observed at middle-and high-doses of ACh (r=0.72, p<0.0001, 15 μg/min vs 10^-7 mol/L; r=0.76, p<0.0001, 30 μg/min vs 10^-6 mol/L). Kaplan-Meier analysis, using the best cut-off values obtained from receiver-operating characteristic curves for CE, revealed that both CBFI and CAFI were significant predictors for CE. Conclusions The BA vasodilator response to optimal ACh dosage can be used as a surrogate prognostic predictor for coronary endothelial function tests in patients with suspected CAD. (Circ J 2006; 70: 49 - 56)

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Background The goal of the present study was to identify predictors of event-free survival in nonischemic dilated cardiomyopathy (NIDCM) patients after administration of angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) and β-blockers. Methods and Results The study group comprised 78 consecutive patients with NIDCM between 1997 and 2002. NIDCM was defined as ejection fraction (EF) <0.40 and left ventricular end-diastolic diameter (LVEDD) >55 mm on echocardiography and normal coronary angiography. The mean EF and LVEDD was 26.3±10.5%, and 62.9±7.1 mm, respectively. Patients were treated with optimal medical therapy including ACEI/ARBs and/or β-blockers and followed up for 35.6±27.8 months. The primary endpoint was either cardiac death or hospitalization because of deterioration of heart failure. Cox's regression analysis was used to establish the association of age, sex, EF, LVEDD, left atrial diameter, cardiac index, pulmonary capillary wedge pressure, QRS duration, severity of mitral regurgitation, body mass index, New York Heart Association class and the presence of atrial fibrillation with these events. During follow-up, 23 patients reached the primary endpoint. In a multivariate analysis, EF (chi-square 5.74, p=0.0166), severity of mitral regurgitation (chi-square 12.31, p=0.0004), and QRS duration (chi-square 11.20, p=0.0008) remained significant predictors. Conclusion In NIDCM patients, prolonged QRS duration is a high risk factor for remodeling and unfavorable events. The severity of mitral regurgitation was also a strong risk predictor. (Circ J 2006; 70: 57 - 62)

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Background This study examined the effects of dual-chamber pacing (DDD) on regional myocardial deformation, as determined by echocardiographic strain and strain rate (SR) imaging, in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods and Results Fourteen patients (11 men, 3 women; mean age 55 ±16 years) who had been on long-term DDD (mean period 7.4±2.1 years) underwent strain and SR imaging. Before and after DDD, the peak strain (%) and SR (s^-1) during systole were assessed in 8 segments in 4 left ventricular (LV) walls. With DDD turned on, peak strain and SR were significantly increased in the basal anteroseptal (strain -10.2±6.8 to -1.0±6.4, p<0.005; SR -0.76±0.46 to 0.05±0.58, p<0.001) and septal segments (strain -11.2±8.9 to -2.2±7.7, p<0.005; SR -0.85±0.54 to -0.19±0.75, p<0.05), but not in the basal posterior (strain -15.0±13.0 to -13.4±9.2, p=NS; SR -1.37±0.57 to -1.93±0.65, p=NS) and lateral segments (strain -18.1±10.2 to -15.7±5.6, p=NS; SR -1.33±0.68 to -0.84±0.88, p=NS). These findings were associated with a modest, but significant, change in the LV pressure gradient (24±12 mmHg to 14±7 mmHg, p<0.001). Conclusions In patients with HOCM, DDD appeared to produce myocardial lengthening in the basal septum during systole, which may have implications for the mechanism of reducing LV outflow obstruction during DDD. (Circ J 2006; 70: 63 - 68)

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Background Hypertrophic cardiomyopathy (HCM) is thought to have a microvolt-level electrical disarrangement in the myocardium that leads to ventricular tachyarrhythmias and sudden cardiac death. Although signal-averaged electrocardiography (ECG) has been used to detect late potential as a parameter of electrical instability, its predictability is not high. The focus of the present study was the ability of high-resolution wavelet transform from beat-to-beat analysis to detect arrhythmogenic substrates and to evaluate its relationship to the severity of ventricular tachycardia. Methods and Results The study group comprised 50 healthy subjects and 50 patients with HCM. The filtered-QRS duration from the signal-averaged ECG, the high-power duration (HPD) and number of disarrangement points (NDP) from the wavelet-transform ECG were measured. When HPD was defined >114 ms and/or NDP >9 points as abnormal, the sensitivity and specificity for ventricular tachycardia was 93.8% and 79.4%, respectively. When a mean ± standard deviation of the HPD in normal subjects was defined as normal, 93.8% of patients with a positive late potential were out of the normal range. Conclusions The newly developed color-display 3-dimensional wavelet transform system showed good time-frequency resolution in analyzing every single beat without signal-averaging. The analysis could be used to detect arrhythmogenic substrates in patients with HCM. (Circ J 2006; 70: 69 - 74)

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Background This study was designed to evaluate the effects of low-frequency electrical stimulation (LFES) on muscle strength and blood flow in patients with advanced chronic heart failure (CHF). Methods and Results Patients with CHF (n=15; age 56.5±5.2 years; New York Heart Association III - IV; ejection fraction 18.7±3.3%) were examined before and after 6 weeks of LFES (10 Hz) of the quadriceps and calf muscles of both legs (1 h/day, 7 days/week). Dynamometry was performed weekly to determine maximal muscle strength (F_max; N) and isokinetic peak torque (PT_max; Nm); blood flow velocity (BFV) was measured at baseline and after 6 weeks of LFES using pulsed-wave Doppler velocimetry of the right femoral artery. Six weeks of LFES significantly increased F_max (from 224.5±96.8 N to 340.0±99.4 N; p<0.001), and also PT_max (from 94.5±41.5 Nm to 135.3±28.8 Nm; p<0.01). BFV in the femoral artery increased after 6 weeks from 35.7±15.4 cm/s to 48.2±18.1 cm/s (p<0.05); BFV values at rest before and after 6 weeks of LFES did not differ significantly. Conclusions LFES may improve muscle strength and blood supply, and could be recommended for the treatment of patients with severe CHF. (Circ J 2006; 70: 75 - 82)

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Background The association between serum uric acid (UA) and the prevalence of hypertension, and the relationship between methylenetetrahydrofolate reductase (MTHFR) polymorphism and hypertension remains unclear. The aim of the present study was to investigate whether the C677T MTHFR mutation genotype (VV) is independently associated with the prevalence of hypertension or blood pressure (BP), and examined any interaction of MTHFR and UA with BP. Methods and Results Participants were randomly selected from all residents (aged 40-69 years) in a rural county of Japan, and the data for the men (n=335) were analyzed. `Hypertension' was defined as systolic BP ≥140 and/or diastolic BP ≥90 mmHg and/or being administered antihypertensive medication. Serum UA level was independently associated with the prevalence of hypertension (odds ratio (95% confidence interval) =2.7 (1.2-5.9), p=0.047) for the highest tertile of serum UA (≥398.5 μmol/L (6.7 mg/dl)) vs that of the lowest tertile (<321.2 μmol/L (5.4 mg/dl)), but the MTHFR mutation was not independently associated with prevalence of hypertension or BP. No interaction of the MTHFR mutation and serum UA with BP was found. Conclusions The mutation of C677T MTHFR was not independently associated with the prevalence of hypertension or BP levels although serum UA was. Furthermore, the relationship between serum UA and BP was not modulated by the MTHFR mutation in Japanese men. (Circ J 2006; 70: 83 - 87)

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Background Pulmonary vein (PV) isolation using a circular catheter creates an entrance block from the left atrium (LA) to the PV, which eliminates paroxysmal atrial fibrillation (PAF). A new approach to PV isolation during distal PV pacing is to use a basket catheter. Methods and Results Fifty consecutive patients with PAF underwent basket-catheter-guided PV isolation. PV pacing was performed from the distal electrode pair of the basket catheter. The exit breakthrough point was targeted for segmental PV isolation. The endpoint was the elimination of bidirectional PV - LA conduction. A repeat ablation procedure was performed in 12 of 14 patients who had recurrence of AF. The recovery of PV -LA conduction was noted in 24 of the 48 PVs, and 5 PVs (21%) had unidirectional block. At 12 months, 80% of patients were free of AF without antiarrhythmic drugs. No PV stenosis >50% was detected at 12 months after the procedure. Conclusions This new approach for PV isolation during distal PV pacing using a basket catheter is useful for confirming bidirectional PV - LA conduction block. PV isolation that creates not only an entrance block but also an exit block at the PV - LA junction may be required to cure paroxysmal AF. (Circ J 2006; 70: 88 -93)

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Background New methods based on nonlinear theory have been developed to give more insight into complex heart rate (HR) dynamics. This study was designed to test the hypothesis that altered HR dynamics, as analyzed with complexity and fractal measures, may precede the spontaneous onset of paroxysmal atrial fibrillation (PAF). Secondly, the difference in the temporal change of these measurements between the different types of atrial fibrillation (AF) was assessed. Methods and Results From 105 Holter tapes in which PAF was recorded, 44 PAF (≥5 min) episodes in 33 patients (22 men, 58±12 years), preceded by sinus rhythm for more than 1 h, were selected and submitted to time-and frequency-domain HR variability analyses, along with detrended fluctuation analysis, approximate entropy (ApEn) and sample entropy (SampEn). The 60 min before the onset of AF were divided into 6 10-min periods and studied using repeated measures ANOVA. PAF episodes were divided into 3 subgroups: an increased HF component and decreased L/H ratio (vagal type, n=20); increased L/H ratio and decreased HF component (sympathetic type, n=14); and non-related type (n=10). None of the time- or frequency-domain parameters showed any significant change before AF in any type of AF. The α₁ showed a tendency to decrease before the onset of AF and the change in α₁ was divergent according to the AF type. The ApEn decreased before the onset of AF (1.005±0.046, 60-50 min before AF to 0.894±0.052, 10-0 min before AF; p=0.032). The SampEn also decreased progressively before the start of AF (1.165± 0.085, 60-50 min before AF to 0.887 ±0.077, 10-0 min before AF, p=0.003). The decrease in both the ApEn and SampEn was irrespective of the AF type. Conclusions A reduction in the ApEn and SampEn, which reflects the nonlinear complexity of HR variability, is a hallmark of altered HR dynamics preceding the spontaneous onset of AF. (Circ J 2006; 70: 94 - 99)

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Background Although brain natriuretic peptide (BNP) is increasingly being used for screening and monitoring of congestive heart failure, its utility in patients with lone atrial fibrillation (AF) is unclear. Methods and Results Plasma BNP levels were measured and comprehensive transthoracic echocardiography was performed in 96 subjects (47: sinus rhythm, 49: AF). Patients with structural heart disease were excluded. Potential determinants of BNP levels were identified by univariate and multivariate analyses. Individuals with AF had higher BNP levels than those with sinus rhythm (150±114 vs 49±61 pg/ml, p<0.001) The left atrial (LA) volume index (r=0.63, p<0.001), the pulmonary artery systolic pressure (r=0.45, p=0.006), and the early mitral inflow velocity (E)/mitral annular velocity (E') (r=0.36, p=0.04) were found to be independently correlated with BNP level. The correlations between BNP level and LA volume index (p=0.001) or E/E' (p=0.03) were unaltered when subjects with sinus rhythm were removed from the analysis. Conclusions BNP levels significantly correlated with LA volume index and E/E' in patients with lone AF, which indicates that the BNP level may reflect early left ventricular dysfunction and LA enlargement in this patient population. (Circ J 2006; 70: 100 - 104)

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Background Although trials of image fusion, such as positron emission computed tomography and multislice spiral computed tomography (MSCT), have already demonstrated clinical usefulness, fusion of the coronary artery image and functional image by MSCT alone has not been reported yet. Here, a new idea of data analysis is proposed in which both regional cardiac function and the responsible coronary arteries can be assessed by a fused image. Methods and Results The study group comprised 5 patients with coronary artery disease. At the first procedure, 3 dimensional (D) volume rendering coronary artery (3D-CTA) was extracted. At the second procedure, the systolic regional wall thickening was calculated and the color 3D functional surface map of systolic wall thickening (3D-SWT) was generated. At the final procedure, 3D-SWT was superimposed on the left ventricular surface with 3D-CTA using a transparency. In all 5 patients, image fusion of the coronary tree and cardiac function was correctly generated. Image fusion can be displayed as clear 3D images, offering better orientation to help assess both the coronary artery and regional function. Conclusions Image fusion of coronary computed tomography angiography and the functional map by MSCT is potentially a new method of assessing both the coronary artery and cardiac function. (Circ J 2006; 70: 105 - 109)

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Background The Japan Society for the Study of Obesity originally proposed a cutoff value of >100 cm² for the intra-abdominal fat area (IFA) as a definition for "visceral fat obesity" in Japanese adults. There are no studies on the cutoff or target values after weight reduction in pre- and post-menopausal women. Methods and Results In the present study 149 pre-menopausal obese women (PreM, 43.3 years, 27.3 kg/m²) and 58 post-menopausal women (PostM, 53.9 years, 27.7 kg/m²) participated in a 14-week weight reduction program. The IFA was measured by computed tomography. The program induced significant reductions in body weight (8.6 kg in PreM and 7.8 kg in PostM). The IFA decreased significantly from 80.4±41.3 to 50.7±23.8 (PreM) and from 115.4±38.0 to 75.7±30.5 (PostM). Conclusions The receiver-operating characteristic curve analyses revealed that the appropriate cutoff values were 80 cm² (PreM) and 110 cm² (PostM) before the program, and after the program the appropriate target values were determined as 60 and 70 cm², respectively. (Circ J 2006; 70: 110 - 114)

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Background Peripheral vascular endothelial dysfunction is an independent predictor of cardiovascular events, and can be assessed noninvasively by measuring reactive hyperemia, either by vascular ultrasound measurement of flow-mediated vasodilatation or, less commonly, by measurement of blood flow using plethysmography. In the present study reactive hyperemia was measured using plethysmography in healthy subjects with multiple cardiovascular risk factors. Methods and Results Reactive hyperemia was measured following 5-min occlusion of the upper arm in 449 healthy subjects (302 men, 147 women, age range 20-70 years) with (n=352) and without (n=97) risk factors such as smoking, hypertension, diabetes mellitus, hypercholesterolemia, obesity, family history of cardiovascular disease, and menopause. Maximum blood flow and minimum vascular resistance in reactive hyperemia did not differ between subjects with and without risk factors regardless of gender. Duration of reactive hyperemia, however, was significantly shorter in subjects with risk factors. Age-adjusted mean value of duration of reactive hyperemia was significantly smaller in men with a smoking habit, diabetes mellitus, hypercholesterolemia or obesity, and in women with smoking habit, hypertension, diabetes mellitus or obesity. The number of risk factors significantly correlated with the duration of reactive hyperemia in both men (r=-0.56, p<0.001) and women (r=-0.62, p<0.001), suggesting that endothelial dysfunction increases with the number of risk conditions clustering in a single individual. Conclusions Duration of reactive hyperemia reflects cardiovascular risk factors and decreases with the number of risk conditions. These findings suggest that the duration of reactive hyperemia measured with plethysmography is potentially useful for assessing endothelial dysfunction. (Circ J 2006; 70: 115 - 123)

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Background Hypertension is a major underlying disease that may cause left ventricular (LV) diastolic dysfunction, even without LV systolic dysfunction, and antihypertensive drugs could affect LV diastolic function. Methods and Results The Effect of Losartan and Amlodipine on Left Ventricular Diastolic Function in Patients With Mild-to-Moderate Hypertension (J-ELAN) study is a multicenter, prospective, randomized trial designed to assess the effects of losartan and amlodipine on LV diastolic function in hypertensive patients with LV diastolic dysfunction in the absence of systolic dysfunction. A total of 300 patients (150 patients in each group) will be enrolled. In addition to Doppler echocardiographic indices of LV diastolic function, changes in LV structure and atherosclerosis of the carotid arteries will be serially assessed. The maximum follow-up period is 18 months. Conclusions This study will provide the characteristic differences in the effects of amlodipine and losartan on LV diastolic dysfunction in hypertensive patients. (Circ J 2006; 70: 124 - 128)

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Background Epidemiological studies indicate a significant link between exposure to environmental air pollution and mortality and morbidity from ischemic heart disease. Because nanoparticles can translocate into blood circulation, the present study aimed to clarify their direct effects on human vascular endothelial cells (ECs). Methods and Results Human umbilical vein ECs (HUVECs) were treated with carbon black (CB), a component of diesel exhaust particles, for 24 h. CB induced cytotoxic morphological changes such as cytosolic vacuole formation, cell disorientation and decreased density. Lactate dehydrogenase assay revealed that CB induced cytotoxic injury in both the cells and plasma membranes. Proliferation assay showed that CB inhibited cell growth. Monocyte chemoattractant protein-1 but not vascular cell adhesion molecule-1 was induced by CB. CB reduced the expressions of connexin37 and endothelial nitric oxide (NO) synthase. Microarray analysis revealed the induction of pro-inflammatory molecules by CB. Conclusions The present results demonstrate for the first time that CB directly affects the endothelium, causing cytotoxic injury, inflammatory responses, and inhibition of cell growth. As EC injury/inflammation and membrane disintegration are related to the initiation of atherosclerosis, and NO is anti-atherogenic and anti-thrombogenic, the direct effects of nanoparticles on ECs may represent one mechanism behind environmental air pollution-mediated atherosclerosis and ischemic heart disease. (Circ J 2006; 70: 129 - 140)

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Background Hyperhomocysteinemia is an independent risk factor of coronary artery disease, but some studies have shown that patients with hyperhomocysteinemia are not prone to atherosclerosis. The aim of this study was to test whether homocysteine increases the production of matrix metalloproteinase-2 (MMP-2) and if extracellular additional magnesium and folic acid alters MMP-2 secretion. Methods and Results Gelatin zymography and western blotting were used to investigate the effects of different homocysteine levels (0-5,000 μmol/L) on MMP-2 production, and the effects of different folic acid concentrations (0-10 μmol/L) and magnesium concentrations (0-3.0 mmol/L) on homocysteine-induced MMP-2 in cultured rat vascular smooth muscle cells. Furthermore, the changes in MMP-2 were compared under various treatments for 24 h, 48 h and 72 h. Homocysteine (50-1,000 μmol/L) increased the production of MMP-2 significantly in a dose-dependent manner and at a high level (5,000 μmol/L) reduced the production of MMP-2. Increased production of MMP-2 induced by homocysteine was reduced by additional extracellular folic acid in a dose-dependent manner. Magnesium also reduced the increase of MMP-2 production induced by homocysteine. Production of MMP-2 under various treatments for 72 h increased more than during 24 or 48 h. Conclusions Homocysteine (50-1,000 μmol/L) significantly increased the production of MMP-2 in a dose-dependent manner. Added extracellular folic acid and magnesium decreased the homocysteine-induced MMP-2 secretion. These data suggest a beneficial effect of folic acid and magnesium on the pathogenesis of coronary artery disease. (Circ J 2006; 70: 141 - 146)

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Newborn case of maternal anti-SSA antibody-induced congenital complete heart block (CCHB) accompanying cardiomyopathy is presented. Unexpectedly, she died of ventricular tachycardia, not bradycardia, 6 days after birth. Autopsy revealed left ventricular cardiomyopathy with endocardial fibroelastosis. Thus, when evaluating fetal cardiac performance in cases of maternal anti-SSA antibody-induced CCHB, it is necessary to pay attention to myocardial attributes such as endocardial hyperplasia. (Circ J 2006; 70: 147 - 149)

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