Inflammation drives the formation, progression, and rupture of atherosclerotic plaques. Experimental studies have demonstrated that an inflammatory subset of monocytes/macrophages preferentially accumulate in atherosclerotic plaque and produce proinflammatory cytokines. T lymphocytes can contribute to inflammatory processes that promote thrombosis by stimulating production of collagen-degrading proteinases and the potent procoagulant tissue factor. Recent data link obesity, inflammation, and modifiers of atherosclerotic events, a nexus of growing clinical concern given the worldwide increase in the prevalence of obesity. Modulators of inflammation derived from visceral adipose tissue evoke production of acute phase reactants in the liver, implicated in thrombogenesis and clot stability. Additionally, C-reactive protein levels rise with increasing levels of visceral adipose tissue. Adipose tissue in obese mice contains increased numbers of macrophages and T lymphocytes, increased T lymphocyte activation, and increased interferon-γ (IFN-γ) expression. IFN-γ deficiency in mice reduces production of inflammatory cytokines and inflammatory cell accumulation in adipose tissue. Another series of in vitro and in vivo mouse experiments affirmed that adiponectin, an adipocytokine, the plasma levels of which drop with obesity, acts as an endogenous antiinflammatory modulator of both innate and adaptive immunity in atherogenesis. Thus, accumulating experimental evidence supports a key role for inflammation as a link between risk factors for atherosclerosis and the biology that underlies the complications of this disease. The recent JUPITER trial supports the clinical utility of an assessment of inflammatory status in guiding intervention to limit cardiovascular events. Inflammation is thus moving from a theoretical concept to a tool that provides practical clinical utility in risk assessment and targeting of therapy. (Circ J 2010; 74: 213-220)

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During a normal lifetime, the heart may beat over 2 billion times, but the mechanisms by which the heart beats are initiated remain a subject of intense investigation. Since the discovery of a pacemaker current (I_f ) in 1978, multiple studies have shown that rhythmic changes in membrane voltage (the "membrane voltage clock") underlie the mechanisms of automaticity. The I_f is a depolarization current activated during hyperpolarization. Therefore, when the cardiac cells recover, the I_f is activated and slowly depolarizes the cell membrane, leading to the onset of action potential. Recent studies, however, suggest that increased intracellular Ca (Ca_i) induced by spontaneous rhythmic sarcoplasmic reticulum Ca release (the "calcium clock") is also jointly responsible for the initiation of the heart beat. Elevated Ca_i activates another ionic current (the sodium-calcium exchanger current or I_NCX), leading to spontaneous phase 4 depolarization. Under normal conditions, both clocks are needed to initiate the heart beat. Malfunction of the clocks is associated with sinus node dysfunction in heart failure and atrial fibrillation. More studies are needed to determine how both clocks work together to initiate heart beat under normal and disease conditions. (Circ J 2010; 74: 221-225)

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Increases in the diameter of small resistance arteries and arterioles occur secondary to processes that can be dependent or independent of changes in membrane potential. Hyperpolarization reduces the opening of voltage-gated calcium channels and thereby the stimulus for contraction of these resistance vessels. The stimulus for smooth muscle cell (SMC) hyperpolarization can occur directly via opening K⁺-channels expressed within those cells, but can also occur in response to stimulation of endothelial cells (ECs). This endothelium-dependent hyperpolarization (EDH) of smooth muscle often occurs in response to agonists that stimulate a rise in the Ca²⁺ concentration of ECs, which in turn can open Ca²⁺-activated K-channels to hyperpolarize the ECs, and if present, patent gap junctions connecting ECs to SMCs (myoendothelial gap junctions) can potentially enable direct electrical coupling. There is also evidence to suggest a diffusible factor or factors hyperpolarizes SMCs (EDHF pathways). Furthermore, whether evoked in ECs or SMCs, hyperpolarization can spread a considerable distance to neighboring cells via gap junctions, causing remote dilatation termed `spreading' or `conducted' dilatation. This process is endothelium-dependent and likely relies on both homo- and heterocellular gap junctions. This review will focus on the cross-talk between ECs and SMCs that coordinates the spread of hyperpolarization and thus modulates smooth muscle tone. (Circ J 2010; 74: 226-232)

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Although 85,000 heart transplantations have been performed worldwide, coronary allograft vasculopathy (CAV), which is a phenomenon of chronic rejection, is still a serious problem. Because CAV involves all the allograft arteries, angioplasty, stenting or bypass grafting are not practical treatment options. Therefore, CAV is the biggest long-term limitation in cardiac allograft recipients. Although the cause of CAV is mostly immunologic, nonimmune pathways also contribute to its development. Several cytokines, chemokines and adhesion molecules play a critical role in the process. Cell adhesion, migration and proliferation of bone marrow progenitor and and other cells are involved in its development. Although there is not an established clinical strategy for preventing or treating CAV, recent investigations have provided some promising methodologies. Progress in DNA technology, such as antisense oligodeoxynucleotides (ODNs) to regulate the transcription of disease-related genes, has an important role in its therapeutic applications. Antisense ODN transfection preventing CAV in experimental cardiac allografts has been reported for the first time. The ODN strategy has not only been useful in the experimental studies, but is also a novel clinical strategy for gene therapy. The pathological and immunological characteristics of CAV and some promising methodologies for prevention of the disease are reviewed. (Circ J 2010; 74: 233-239)

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Although preventive pharmacological therapies effectually reduce the risk of cardiovascular events, acute coronary syndrome (ACS) remains a leading cause of morbidity and mortality in our country, Japan. Disruption of atherosclerotic vulnerable plaques and flow-limiting thrombus formation in non-stent segments of native coronary arteries are considered a main mechanism of ACS. In addition, stent thrombosis originating from implanted metallic coronary stents, so-called vulnerable stents, occasionally appears as ACS in the clinical settings. Coronary angioscopy is a unique imaging modality permitting direct visualization of luminal structures, such as atherosclerotic plaque, thrombus, stent struts, and proliferating neointima. On the basis of accumulated angioscopic findings, intense yellow plaques and stents without neointimal coverage are considered vulnerable plaques and vulnerable stents, respectively. In contrast, morphological disappearance of vulnerable plaques or vulnerable stents by pharmacological and trans-catheter therapies imply stabilization of the plaques or stents. Hence, angioscopic assessment for vulnerability (or stability) of atherosclerotic plaques and implanted stents might be useful for risk classification in the future events of ACS. To evaluate serial changes of coronary lumen after pharmacological and catheter interventions using angioscopy might also provide important information on potential benefits and surrogate endpoints of the therapies and on patients' management. (Circ J 2010; 74: 240-245)

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Background: An ECG predictor of ablation success has not been determined for difficult cases of outflow tract ventricular tachycardia/ventricular premature contractions (OT-VT/VPC). Methods and Results: ECG analysis and radiofrequency catheter ablation (RFCA) were performed in 70 patients with OT-VT/VPC. The peak deflection index (PDI) was determined in the inferior lead presenting the tallest R wave by dividing the time from QRS onset to peak QRS deflection by total QRS duration. In 10 (14%) of the 70 patients, RFCA performed at a septal or epicardial site was unsuccessful (group 1), but was successful in the remaining 60 patients (group 2). Neither activation time (35±15 ms vs 40±12 ms, P=0.3) nor QRS duration (141±19 ms vs 137±19 ms, P=0.6) were significantly different between groups 1 and 2. However, PDI was significantly higher in group 1 than in group 2 (0.62±0.06 vs 0.55±0.06, P=0.002). A PDI >0.6 identified unsuccessful OT-VT/VPC with 80% sensitivity and 90% specificity, and may indicate that the origin of the OT-VT/VPC is deep within the ventricular septum or at an epicardial site. Conclusions: A PDI >0.6 is more likely to be associated with a higher rate of RFCA failure. (Circ J 2010; 74: 256-261)

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Background: Although clinical studies have suggested a link between inflammation markers and atrial fibrillation (AF), it is still unclear whether local immunologic responses actually exist in human atria during AF. Methods and Results: To address this point, human left appendages were obtained from 16 patients who underwent cardiac surgery (5 with sinus rhythm (SR) and 11 with AF) and subjected to immunohistochemical analysis. In all the AF specimens, adhesion and migration of CD45-reactive cells were consistently observed predominantly in the atrial endo- and subendomyocardium and more prominently than in SR. Most of them were immunologically active CD68-positive macrophages, whereas CD3-positive T cells infiltrated to a lesser extent. Scavenger-receptor A staining revealed maturation of macrophages not in the endocardium but in the midmyocardium, a gradient from endo- to midmyocardium. In the endocardium, along with adhesion molecules (intracellular adhesion molecule-1 and vascular cell adhesion molecule-1), a chemotactic protein-1, which facilitates the recruitment, was more abundantly expressed in AF than in SR. Cytokines including transforming growth factor-β and interleukin-6 were frequently expressed by these macrophages. Conclusions: These observations collectively imply active adhesion and recruitment of macrophages across the endocardium in human fibrillating atria, thereby supporting the concept of local immunologic inflammatory responses around the atrial endocardium of AF. (Circ J 2010; 74: 262-270)

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Background: In the present study, clarification of the prevalence of the Brugada-type electrocardiogram (ECG) and the incidence of spontaneous ventricular fibrillation (VF) that occurred with the Brugada-type ECG in patients with sick sinus syndrome (SSS) was determined. Methods and Results: A total of 487 consecutive patients (men 45%, mean age 69.9±12.3 years), who were defined as having an indication for cardiac pacemaker (PM) for SSS, were investigated. The ECG before an initial PM implantation and occurrence of VF or sudden cardiac death (SCD) was examined retrospectively. Brugada-type ECG was found in 14 patients (2.87%) including 4 (0.82%) with type 1 and 10 (2.05%) with type 2. During the follow-up period of 7.2±5.4 years, 2 out of the 4 patients with type 1 ECG had experienced a VF episode after the device implantation. In 10 patients with type 2 ECG, none had VF or SCD. The incidence of spontaneous VF (Brugada syndrome) in SSS patients was calculated as 14.1 per 100 person-years with type 1 ECG. Conclusions: The prevalence of typical Brugada-type (type 1) ECG in SSS patients seems to be higher compared with the general population. In addition, SSS patients with the typical Brugada-type ECG might be a high risk for spontaneous VF. (Circ J 2010; 74: 271-277)

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Background: A recently introduced tricuspid annuloplasty ring, the MC³ ring, has a 3-dimensional form that is designed to remodel the tricuspid valve annulus. The aim of this study was to investigate its clinical performance. Methods and Results: From December 2004 to April 2008, 103 patients underwent tricuspid annuloplasty using the MC³ ring (mean age, 52±13 years; 63.6% women). The average preoperative tricuspid regurgitation (TR) grade was 2.5±0.8, and the mean preoperative systolic pulmonary artery pressure was 48.4±15.0 (24-88) mmHg; the mean follow-up was 26.7±11.2 (0-52) months. One patient died after surgery (1.0%), because of cor pulmonale. No MC³ ring-related complications, such as, atrioventricular block, ring dehiscence or thromboembolism, were encountered. Predischarge echocardiography showed a significant decrease in the TR grade (2.5±0.8 to 0.8±0.8, respectively; P<0.001). After a median 15 months, the mean TR grade was stable (0.9±0.8). The mean systolic pulmonary artery pressure was also lower than its preoperative value (33.9±7.9 vs 48.4±15.0 mmHg, respectively; P<0.001). Conclusions: The MC³ ring provides good mid-term clinical and echocardiographic results for TR. However, long-term follow-up is mandatory to confirm the stability of this procedure. (Circ J 2010; 74: 278-283)

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Background: Minimally invasive robot-assisted cardiac surgery is generally performed nowadays. To avoid the interference of a superior vena cava (SVC) cannula during surgery, it should be inserted before the operation. The position of this cannula is very important because it can cause poor venous drainage during operation. The proper position of the SVC cannula was investigated in the present study. Methods and Results: The position of the SVC cannula using the transesophageal echocardiography (TEE) and chest X-ray in 45 patients was ascertained. The distances from the SVC cannula tip to the carina, sternal end of the right clavicle and the lower margin of the T4 vertebral body on chest X-rays were measured. The mean depth of the SVC cannula was 142.0±11.6 mm. The correlation coefficients of cannula depth with sex, weight and height were 0.519, 0.399 and 0.382, respectively. Conclusions: The appropriate depth of an SVC cannula has weakly positive relationships with sex, weight and height. The results of the present study suggest that chest X-rays might be necessary to confirm the appropriate location of the cannula and that TEE might be the method of choice for correct positioning of the SVC cannula in minimally invasive robot-assisted cardiac surgery. (Circ J 2010; 74: 284-288)

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Background: Major pulmonary embolism (PE) is a life-threatening disorder associated with high mortality and morbidity. The clinical characteristics and outcomes in major PE managed by a well-organized cardiac care regional urban network and hospitals have not been clarified and were examined in the present study. Methods and Results: Data from the Tokyo CCU Network registered cohort in 2005-2006 were analyzed. Among 193 patients with major PE and known severities and outcomes, 42 patients had massive PE, defined as cardiogenic shock or cardiac arrest. The median time from symptom onset to CCU admission was 16.3 h. The in-hospital mortality of the 124 patients who received reperfusion therapy was lower than that of the 69 patients that did not receive reperfusion therapy (11.3% vs 18.8%; P=0.15). In multiple logistic regression analyses after adjusting for advanced age and sex, reperfusion therapy was selected as a significant predictor for in-hospital death (adjusted odds ratio, 0.34; 95%CI, 0.12-0.95; P=0.039), in addition to massive type (adjusted odds ratio, 14.02; 95%CI, 4.71-41.76; P<0.0001). Conclusions: Early transport and specific reperfusion therapy for major PE were effectively performed by the Tokyo CCU Network, suggesting the efficacy of a specialty management system for major PE. (Circ J 2010; 74: 289-293)

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Background: There is still conflicting evidence that green tea may protect against coronary atherosclerosis therefore the present study investigated the association between green tea consumption and arteriographically determined coronary atherosclerosis in a Chinese population. Methods and Results: The study population consisted of 520 consecutive patients (379 men and 141 women) who underwent coronary arteriography for the first time. Patients were divided into 2 groups (Non-coronary artery disease [CAD] and CAD groups) according to the results of coronary arteriography. After adjusting the established and potential confounders, green tea consumption was associated with a reduced risk of CAD in male patients, with an adjusted odds ratio (OR) of 0.62 (95% confidence interval, 0.38-1.01) compared with those who did not drink green tea. Compared to non-tea drinkers, the adjusted ORs were 1.09 (0.61-1.96) in male patients consuming less than 125 g of dried green tea leaves per month, 0.36 (0.19-0.71) for 125-249 g per month and 0.36 (0.17-0.73) for ≥250 g per month, with a statistically significant test for trend (P<0.001). Similar dose-response relationships were also observed for frequency, duration, concentration and starting age of green tea drinking in male patients. In female patients, no inverse association was found between green tea consumption and CAD. Conclusions: Green tea consumption can protect against the development of coronary atherosclerosis in Chinese male patients. (Circ J 2010; 74: 294-300)

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Background: The etiology of anemia is still unclear in patients with chronic heart failure (CHF). Hepcidin is an iron regulatory peptide that is synthesized in the liver to suppress iron absorption and utilization. Hepcidin synthesis is suppressed by anemia, hypoxia and erythropoiesis, and induced by inflammation. Inflammatory cytokines, such as interleukin-6 (IL-6), increase the synthesis of hepcidin, resulting in anemia of inflammation (AI). The serum hepcidin concentration in CHF patients with anemia was measured in order to better understand anemia in CHF. Methods and Results: Serum hepcidin-25, erythropoietin (EPO), ferritin and IL-6 concentrations were measured in 61 CHF patients. Among these patients, 36 patients had anemia. A group of 16 patients without cardiac disease or anemia were recruited as controls. Serum IL-6 and EPO were higher and hepcidin-25 was lower in CHF patients with anemia than in controls. Hepcidin-25 correlated with EPO and ferritin but not with IL-6. Results of multivariable regression analysis showed that independent predictors of serum hepcidin-25 included EPO and ferritin but not IL-6. Conclusions: Serum hepcidin-25 concentrations were regulated by iron storage and erythropoiesis but not by IL-6 in CHF patients with anemia. These findings might indicate that AI is a minor cause of anemia in CHF. (Circ J 2010; 74: 301-306)

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Background: Defecation syncope (DS) and micturition syncope (MS) are daily excretion-related syndromes that are both classified as situational. However, their clinical features seem to be very different, so the present comparative study aimed to clarify those of DS. Methods and Results: The study population consisted of 20 consecutive patients with DS and 37 consecutive patients with MS. The DS patients were significantly older than the MS patients (63±15 vs 52±17 years, P=0.026). Gender was significantly different (P=0.026): women predominated in the DS group (60%) whereas men more commonly had MS (70%). The diurnal distribution of syncope differed (P=0.0054): 88% of MS episodes occurred between 6 pm and 6 am, whereas DS occurred almost equally throughout the 24 h. Syncope after drinking alcohol was less common with DS (10%) than with MS (60%) (P=0.0003), whereas gastrointestinal tract (GIT) symptoms as a premonitory sign were more common with DS (55%) than with MS (3%) (P<0.0001). Positive responses to head-up tilt testing did not differ between the DS and MS groups. Conclusions: DS tends to occur in elderly women and without any significant daily distribution. Alcohol-related syncope was uncommon in patients with DS, and preceding GIT symptoms may be important as predictors or triggering factors. (Circ J 2010; 74: 307-311)

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Background: The aims of this study were to evaluate subclinical regional right ventricular (RV) dysfunction in newly diagnosed obstructive sleep apnea (OSA) patients without systemic and pulmonary arterial (PA) hypertension, and to correlate OSA severity to RV dysfunction, using both velocity vector imaging (VVI)-derived strain imaging and tissue Doppler imaging (TDI). Methods and Results: The OSA group consisted of 27 patients and the control group consisted of 26 healthy participants. All participants underwent 24-h ambulatory blood pressure monitoring. Peak systolic myocardial velocities, strain, and strain rate (SR) were determined at the basal and mid segments of the RV free wall by VVI. Additionally, RV myocardial velocities were assessed by pulsed-wave TDI. Patients with OSA had significantly impaired VVI-derived peak systolic myocardial velocities, strain, and SR (P<0.0001 for all). RV isovolumic acceleration (IVA) was the only TDI-derived parameter that was significantly impaired (P<0.0001). RV IVA (r=-0.512, P<0.0001), RV mid free wall strain (r=0.568, P<0.0001) and SR (r=0.519, P<0.0001) revealed the best correlations with apnea hypopnea index (AHI). Conclusions: Subclinical RV dysfunction is present in OSA patients despite normal systemic and PA pressures. Tissue Doppler-derived RV IVA and VVI-derived RV deformation can accurately recognize and quantify RV function abnormalities in this subgroup of patients. (Circ J 2010; 74: 312-319)

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Background: The differences between using Sirolimus-eluting stents (SESs) and Paclitaxel-eluting stents (PESs) in the vascular response at 9 months after implantation were examined with optical coherence tomography (OCT). Methods and Results: OCT was carried out in 33 SESs [33 patients, 19 with acute coronary syndrome (ACS) and 14 with stable angina pectoris (SAP)] and 27 PESs (27 patients, 15 with ACS and 12 with SAP) at 9 months after stent implantation. Stent strut coverage and apposition at each strut were evaluated. The frequency of uncovered struts was significantly higher in SES (12.5±15.2 vs 4.9±7.9 %, P=0.01). The incidence of complete covered stents with neointima was 9.1% (3/33) in SES and 29.6% (8/27) in PES (P=0.05). The pattern of neointima in PES was more heterogeneous than that in SES (1.3±0.5 for SES vs 2.0±0.6 for PES, P<0.001). The intracoronary thrombus was frequently detected in SES [10 (30.3%) in SES vs 5 (18.5%) in PES, P=0.29]. Conclusions: Uncovered struts were frequently observed in SES, but the pattern of neointima was more heterogeneous in PES at 9 months. In addition, stent coverage was incomplete in both stent groups at 9 months after stent implantation. (Circ J 2010; 74: 320-326)

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Background: The serum level of fatty-acid-binding protein 4 (FABP4) increases in patients with metabolic syndrome (MetS), so the relationship between FABP4 and MetS among patients with coronary artery disease (CAD) was investigated in the present study. Methods and Results: Fasting blood samples were obtained from 98 CAD patients. MetS and its components were defined using the diagnostic criteria of the International Diabetes Federation; 50 CAD patients (51.0%) had MetS. The fasting level of FABP4 positively correlated with MetS (P=0.037) and serum levels of FABP4 correlated with a number of MetS criteria (P=0.035). Univariate linear regression analysis showed that body fat mass (R=0.234; P=0.020) and the levels of triglycerides (R=0.348; P<0.001), and low-density lipoprotein-cholesterol (R=0.217; P=0.032) positively correlated with the serum level of FABP4, whereas the level of high-density lipoprotein-cholesterol (R=-0.243; P=0.016) negatively correlated with it. Multivariate forward stepwise linear regression analysis of the significant variables showed that the level of triglycerides (β=0.348, R²=0.121, P<0.001) was the independent predictor of fasting serum level of FABP4. Conclusions: Among CAD patients in the present study, the fasting level of FABP4 positively correlated with MetS and serum levels of FABP4 correlated with a number of MetS criteria. (Circ J 2010; 74: 327-331)

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Background: The relationship between plasma biomarkers and vulnerable plaque is not well understood. Methods and Results: The 188 patients who underwent 3-vessel virtual histology (VH) intravascular ultrasound (IVUS) with peripheral blood sampling were enrolled. Plasma levels of matrix metalloproteinase 2 and 9 (MMP-2, -9), tissue inhibitor of metalloproteinase-1, adiponectin, and macrophage migration inhibitory factor were measured. VH-IVUS-derived thin cap fibroatheroma (VH-TCFA) was defined as a necrotic core >10% of plaque area in the presence of >40% plaque burden. There were 38 patients with ruptured plaque and 150 patients without (107 patients with VH-TCFA, 43 patients without VH-TCFA) in culprit/target lesions. Among the biomarkers, only the MMP-9 level was significantly higher in patients with ruptured plaque (P=0.002). In the subgroup without ruptured plaque, significant differences in the levels of several biomarkers were not observed between patients with and without VH-TCFA. In both culprit/target and nonculprit/non-target vessels, the MMP-9 level showed a weak correlation with the total number of ruptured plaques (r=0.231, P=0.002). Conclusions: Among the biomarkers tested in this study, the MMP-9 level was significantly higher in patients with ruptured plaque. However, measurement of several biomarkers, including MMP-9, was incapable of predicting the presence of VH-TCFA. (Circ J 2010; 74: 332-336)

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Background: Recent studies suggest that fractalkine (FKN or CX3CL1) and its cognate receptor, CX3CR1, play a role in atherogenesis, so the relationship between coronary plaque rupture, as observed by preintervention optical coherence tomography, and plasma levels of FKN and CX3CR1 was investigated in this study. Methods and Results: The study population consisted of 46 patients with unstable angina pectoris (UAP), 30 patients with stable angina pectoris, and 25 healthy controls. The UAP patients underwent a preintervention optical coherence tomography study, which revealed that the number of patients with and without plaque rupture at the culprit site was 27 (rupture group) and 19 (non-rupture group), respectively. Plasma levels of soluble FKN (sFKN) and CX3CR1 were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively. The plasma levels of sFKN were significantly increased in UAP patients with plaque rupture compared with patients in the other groups. Multiple logistic regression analysis showed that CD14⁺CD16⁺CX3CR1⁺ monocytes and CD3⁺CX3CR1⁺ lymphocytes were independent predictors of the presence of ruptured plaque. Conclusions: Increases in the FKN level and the number of CX3CR1-expressing mononuclear cells might contribute to coronary plaque rupture. (Circ J 2010; 74: 337-345)

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Background: In the current study, the effects of moderate to severe chronic obstructive pulmonary disease (COPD) on coronary blood flow in patients with angiographically proven normal coronary arteries was evaluated. Methods and Results: A total of 85 patients with moderate to severe COPD and 39 age- and sex-matched control partcipants, who underwent diagnostic coronary angiography and found to have normal epicardial coronary angiogram constituted the COPD and control groups, respectively. The 2 groups were compared for Thrombolysis In Myocardial Infarction (TIMI) frame counts in each major coronary artery. The TIMI frame count of the COPD group was significantly higher than that of control group for all 3 major individual coronary arteries: left anterior descending (corrected), 37±13 vs 20±4; right coronary artery, 32±14 vs 21±4; and left circumflex artery, 34±12 vs 20±5, (P<0.001 for all). In addition, TIMI frame counts in individual coronary arteries were found to be positively correlated with forced expiratory volume 1 s percent, serum high sensitive C-reactive protein and fibrinogen concentrations, in the COPD group. Conclusions: Our findings suggest that an increased slow coronary flow might be a manifestation of harmful effects of COPD on the coronary circulation, regardless of the underlying mechanism. (Circ J 2010; 74: 346-352)

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Background: Oxidative stress is thought to play an important role in age-induced atherogenesis. Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme that is localized in mitochondria and protects macrophages against apoptosis induced by oxidized low density lipoprotein (oxLDL). We previously reported that genetic polymorphism of MnSOD modifies mitochondrial MnSOD (mtMnSOD) activity and increases the risk of coronary artery disease. In this study, we investigated the association of mtMnSOD activity with aging. Methods and Results: Blood samples were taken from 69 healthy participants aged 20-52. The MnSOD genotype was analyzed using real-time polymerase chain reaction. Leukocyte mtMnSOD activity was measured by inhibition of WST-1. Macrophages were treated with oxLDL and the apoptotic cells were counted. mtMnSOD activity was inversely correlated with the age of the participant regardless of the MnSOD genotype. The percentage of apoptotic macrophages after incubation with oxLDL correlated with age. Thus, the percentage of apoptotic macrophages after incubation with oxLDL was inversely related to mtMnSOD activity. Lecithinized SOD, which can easily transfer into cells, improved the tolerance of macrophages against oxLDL. Conclusions: mtMnSOD activity decreases with age, thereby reducing the tolerance of macrophages against oxLDL-induced apoptosis. Our data may provide an important clue to clarify the mechanisms of age-induced atherosclerosis. (Circ J 2010; 74: 353-360)

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Background: There are difficulties in transcatheter closure of patent ductus arteriosus (PDA) in infants. Methods and Results: The 46 infants (mean age 6.2±2.7 months; mean body weight 6.3±1.6 kg) who underwent PDA closure using the Amplatzer duct occluder (ADO). The indication for using an ADO was a ductus diameter ≥2.5 or 3 mm. Device diameter selected was 1-3 mm larger than ductal diameter. The mean systolic pulmonary artery pressure was 40.9±18.2 mmHg. The mean Qp/Qs ratio was 3.1±1.2. The mean ductus diameter was 3.3±0.8 mm. ADO was successfully deployed in 45 patients. Failure occurred in 1 case. The mean diameter of device used was 5.4±1.1 mm. No severe complications occurred. At the 1-month echocardiographic follow-up, a small residual shunt was present in 4 of 45 patients and had disappeared in all 4 patients at the 3-month follow-up. One patient developed a moderate degree of left ventricular outflow tract obstruction 2.3 years after the procedure. Conclusions: Transcatheter closure of PDA in infants using the ADO is a safe and effective method. (Circ J 2010; 74: 361-364)

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Background: Patients with peripheral arterial occlusive disease (PAD) experience deteriorating ambulatory function and consequently impaired quality of life (QOL). QOL in patients receiving prostaglandin E₁ in lipid microspheres (lipo-PGE₁; Liple^®) for the treatment of PAD has not been evaluated using the Japanese version of the Walking Impairment Questionnaire (WIQ). Methods and Results: Data from 169 patients (98 men, 71 women; mean [median] age, 74±10 [74] years) with an ankle-brachial pressure index <0.9 were analyzed. WIQ scores and symptom scores significantly improved after lipo-PGE₁ treatment (P<0.01). Physicians' assessments of global improvement significantly correlated with all 4 WIQ subscales (R<- 0.31). Conclusions: WIQ is a valid tool for evaluating therapeutic response in patients with PAD. Lipo-PGE₁ improves QOL as evaluated by patients themselves. (Circ J 2010; 74: 365-370)

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Background: Previous studies have reported a high prevalence of autoimmune thyroid disease (AITD) in adult patients with pulmonary arterial hypertension (PAH). The aim of this retrospective study was to determine the prevalence of AITD in children and adolescents with idiopathic PAH (IPAH). Methods and Results: The study group included 16 patients who had been diagnosed as having idiopathic PAH when they were younger than 15 years old; all were younger than 20 years of age. Thyroid function and antithyroid antibody levels were examined regularly at 6-12-month intervals and when there were clinical signs of thyroid dysfunction. In total, 7 patients (44%) had AITD; 2 patients developed Graves' disease, 2 developed silent thyroiditis, and 3 had antithyroid antibodies with euthyroidism. The duration after PAH onset and the prostacyclin (PGI₂) treatment period were significantly longer in patients with AITD (7.6±2.1 and 7.4±2.3 years, respectively) than in patients without AITD (5.0±1.1 and 4.8±1.2 years, respectively; P<0.01 and P<0.05). Conclusions: The prevalence of AITD is high in children and adolescents with IPAH, so evaluation of thyroid function is important to prevent deterioration of right heart failure. (Circ J 2010; 74: 371-374)

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Background: The prognostic implications and surgical benefit of isolated significant tricuspid regurgitation (TR) and prognostic factors in patients with TR were investigated. Methods and Results: In 870 consecutive patients with significant isolated TR, all-cause mortality was analyzed over 4.9±2.9 years. It was found that the survival rate tended to be higher in the 57 patients who underwent tricuspid valve (TV) surgery than the 813 patients who did not by using propensity-score matching (P=0.068), although it was not significant. Of the 813 patients that did not undergo TV surgery, the 5-year survival rate was 74%. According to the Cox proportional hazards model, the initial TR jet area (hazard ratio [HR], 1.044; 95% confidence interval [CI], 1.016-1.073), pulmonary artery systolic pressure (HR, 1.024; 95%CI, 1.017-1.032) and presence of right ventricular (RV) dysfunction (HR, 2.256; 95% CI, 1.329-3.828) were predictors of mortality independent of patient age and presence of diabetes mellitus and renal failure in medically managed patients. Conclusions: In patients with isolated significant TR, there was a tendency, although not significant, towards a higher survival rate after TV surgery. The severity of TR and pulmonary hypertension, and the presence of RV dysfunction are independent prognostic factors in medically managed patients. Further prospective randomized studies are necessary to demonstrate the benefit of TV surgery in these poor prognostic populations. (Circ J 2010; 74: 375-380)

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(Circ J 2009; 73: 2270 - 2275)

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(Circ J 2010; 74: 195 - 202)

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