Heart failure (HF) results in substantial morbidity, mortality, and costs, yet quality of care varies widely and is frequently inadequate. Performance improvement registries have been developed to improve the quality of care and outcomes for patients with HF in both the inpatient and outpatient settings. HF registries in the United States include ADHERE, OPTIMIZE-HF, GWTG-HF, and IMPROVE HF. These registries collect data on clinical characteristics, admission, hospital, discharge, and/or outpatient care, as well as outcomes. Web-based tools that provide real-time feedback of performance and other quality measures benchmarked to other sites and national data are frequently utilized. Process-of-care improvement tools, including evidence-based clinical decision support, customizable order sets, and patient education are also used. Participation in performance improvement registries has been associated with substantial improvements in the use of guideline-recommended therapies for HF in both the inpatient and outpatient settings. Conformity with HF quality measures has also been shown to improve and disparities in care have also been reduced or eliminated. There have also been improvements in clinical outcomes. This paper reviews the evidence that participation in HF performance improvement registries is associated with improved use of guideline-recommended HF therapies, better conformity with quality measures, and improved outcomes in patients with HF. (Circ J 2011; 75: 1783-1790)

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It has been established that oxidative stress plays a crucial role in the development and progression of vascular diseases. Besides the mitochondria, the NADPH oxidase/Nox family proteins are now thought to be important origins of the reactive oxygen species that underlie various vascular disease states, such as hypertension, atherosclerosis, angiogenesis, and ischemia/reperfusion injury. This review summarizes the basis of vascular Nox proteins and discusses their pathophysiological roles in the vascular system. (Circ J 2011; 75: 1791-1800)

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Pulmonary hypertension (PH) is a fatal disease caused by small pulmonary artery obstruction from vascular proliferation and remodeling. PH is characterized by elevated pulmonary arterial pressure and increased pulmonary vascular resistance, frequently leading to right-sided heart failure and death. The classification of PH has been recently updated to include 5 major categories of the disorder, are as: Group 1, pulmonary arterial hypertension (PAH); Group 2, PH due to left heart disease; Group 3, PH due to lung diseases and/or hypoxia; Group 4, chronic thromboembolic PH (CTEPH); and Group 5, others. Recently, significant progress has been made in the understanding of the pathophysiology, diagnosis and treatment of PH. Regarding the pathophysiology of the disorder, direct evidence for Rho-kinase activation in the pulmonary artery from PAH patients has been provided. Regarding diagnosis, optical coherence tomography is useful as a new differential diagnostic tool for distal type CTEPH vs. PAH. Regarding treatment, in addition to the conventional therapy, several new drugs are under clinical trial, including fasudil (a Rho-kinase inhibitor), riosiguat (a soluble guanylate cyclase activator), and imatinib (a tyrosine kinase inhibitor). In addition, pulmonary angioplasty and intensive immunosuppressive therapy may be effective for CTEPH and connective tissue disease-associated PAH, respectively. We briefly review the recent progress in the management of PH. (Circ J 2011; 75: 1801-1810)

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The heart works as a driving force to deliver oxygen and nutrients to the whole body. Interrupting this function for only several minutes can cause critical and permanent damage to the human body. Thus, heart failure (HF) or attenuated cardiac function is an important factor that affects both patient's the quality of life and longevity. Numerous clinical and basic studies have been performed to clarify the complex pathophysiology of HF and to develop effective therapies. Modulating the β-adrenergic receptor-mediated signaling pathway has been one of the most crucial targets for HF therapy. Impressively, recent reports identified p53, a well-known tumor suppressor, as a major player in the development of HF. The present review highlights the apoptosis of cardiomyocytes, which is one of the important mechanisms that leads to HF and can be induced by both β-adrenergic signaling and p53. Consideration of the cross-talk among these major pathways will be important when developing effective and safe therapies for HF. (Circ J 2011; 75: 1811-1818)

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Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a serious disease with a high mortality but its management is limited. The aim of this study was to investigate specific target sites for therapy in order to find potential management strategies for CPVT. Methods and Results: The mutant Ryanodine receptor 2 (RyR2) with reduced stored-overloaded-induced Ca²⁺ release (SOICR) threshold was incorporated into the Luo-Rudy dynamic (LRd) cell model to elucidate the underlying pathologies of CPVT. The simulations reveal that β-adrenergic stimulation increased the Ca²⁺ load in cardiac myocyte, which facilitates spontaneous SR Ca²⁺ leakage, resulting in triggered arrhythmias. Varied blockade (from 0% to 90%) in specific ion channels, including the Na⁺/Ca²⁺ exchanger (I_NaCa), fast Na⁺ channel (I_Na), RyR2 receptor (I_rel), Ca²⁺-ATPase (SERCA) (I_up) or L-type Ca²⁺ channel (I_Ca(L)),was performed to simulate the action of specific drugs on target sites. Blockade of the I_NaCa (≤10% blockade), in contrast to the I_up (≤30% blockade), I_Ca(L) and I_Na (≤40% blockade), and followed by I_rel (≤80% blockade), was most effective in suppressing the triggered arrhythmias in CPVT. Specifically, dual blockade of I_Ca(L)/I_up, I_Na/I_rel or I_Ca(L)/I_rel had a synergistic effect in CPVT management. Conclusions: Blockade of I_NaCa appears to be the most efficacious target for CPVT management. Dual blockade of I_Ca(L)/I_up, I_Na/I_rel or I_Ca(L)/I_rel has a synergistic effect in CPVT treatment. (Circ J 2011; 75: 1833-1842)

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Background: Eicosapentaenoic acid (EPA), the major n-3 fatty acid in fish oil, exerts cardioprotective effects against ischemic heart disease; however, the detailed mechanisms remain to be elucidated. Rho-kinase plays an important role in the pathogenesis of cardiovascular diseases including ischemia-reperfusion (I/R) injury. Thus, the hypothesis that long-term EPA treatment ameliorates myocardial I/R injury through Rho-kinase pathway inhibition in pigs in vivo was investigated. Methods and Results: Male pigs were treated with either a control chow or EPA (600·mg·kg^-1·day^-1) for 3 weeks (n=8 each) and were subjected to myocardial ischemia by 90-min occlusion of the left circumflex coronary artery and subsequent 60-min reperfusion. The EPA group had an increased EPA level in red blood cells (4.4±0.3mol%). The EPA treatment significantly ameliorated myocardial I/R injury, including regional wall motion abnormality (EPA 5.3±3.6 vs. control 35.1±3.8 unit, P<0.0001), left ventricular ejection fraction (EPA 43±9% vs. control 32±7%, P<0.05), occurrence of ventricular arrhythmias (EPA 181±73 vs. control 389±51 events, P<0.0001) and histological accumulation of inflammatory cells (P<0.01). Importantly, the EPA treatment significantly inhibited myocardial Rho-kinase activity (assessed by the extent of the myosin-binding subunit phosphorylation) (EPA 0.47±0.11 vs. control 0.77±0.14, P<0.05) and preserved myocardial eNOS activity (EPA 0.56±0.13 vs. control 0.23±0.07, P<0.01) with a significant correlation noted between them. Conclusions: Long-term treatment with EPA ameliorates I/R injury partly through Rho-kinase pathway inhibition in vivo. (Circ J 2011; 75: 1843-1851)

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Background: Guidelines recommend warfarin as the standard of care for patients with atrial fibrillation (AF) at moderate or high risk for stroke. This phase II study assessed the effects of 2 doses of the factor Xa inhibitor apixaban vs. warfarin in Japanese patients with non-valvular AF. The composite primary endpoint was major and clinically relevant non-major (CRNM) bleeding. Methods and Results: Two hundred and twenty-two patients with AF and 1 or more additional risk factors for stroke were randomized (1:1:1) to double-blind apixaban 2.5 or 5mg b.i.d. or open-label warfarin (target international normalized ratio 2.0-3.0; 2.0-2.6 if age ≥70 years) for 12 weeks. The primary endpoint occurred in 1 patient (1.4%) in each apixaban group and 4 (5.3%) warfarin patients. There were no strokes, systemic emboli, myocardial infarctions, or deaths in either apixaban group. The warfarin group had 2 ischemic strokes and 1 subarachnoid hemorrhage, but there were no deaths. Major and CRNM bleeds each occurred with higher frequency in the warfarin group vs. either apixaban group. Most adverse events were mild or moderate. No patients had hepatic aminotransferase elevations greater than 3 times the upper limit of normal. Conclusions: In Japanese patients with AF, apixaban 2.5 and 5mg b.i.d. were well tolerated over 12 weeks. A global phase III trial, which includes Japanese patients, is ongoing (ClinicalTrials.gov Identifier NCT00787150). (Circ J 2011; 75: 1852-1859)

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Background: Radiofrequency catheter ablation (RF) has recently become widely available for the treatment of atrial fibrillation (AF) and has broadened treatment options while confusing the selection of medication therapy or RF. Methods and Results: Two drugs for the maintenance of sinus rhythm (Ry) and 2 drugs for control of the pulse rate (Ra) were selected and the costs of medication therapy were calculated. RF procedures were grouped into 2 groups each for persistent or paroxysmal AF (RF) and for chronic AF (RFChr), according to the cost of the devices used. The calculated cost of medication therapy was 5,270-23,560 yen per month. The calculated cost of RF procedures was 1,063,200-2,029,640 yen. The costs of RF corresponded to those of Ry for 3.8-14.3 years. The costs of RFChr corresponded to those of Ra for 16.6-63.9 years. The treatment of complications ranged from 360,000 to 1,241,500 yen. Conclusions: From the aspect of medical costs and complications, RF should be considered for the treatment of patients with AF detected early or early-stage AF, whereas treatment for its complications should be given priority in patients with chronic AF associated with reduced cardiac function. (Circ J 2011; 75: 1860-1866)

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Background: The aim of the present study was to assess immediate and long-term clinical outcome of Chinese patent foramen ovale (PFO) patients with paradoxical embolism who underwent transcatheter PFO closure. Methods and Results: One hundred and ninety-two patients underwent transcatheter PFO closure for secondary prevention of thromboembolic events (TE). During the procedure, 7 patients had frequent atrial premature beats or transient atrial tachycardia in implantation and 1 patient had a transitory ST-elevation in leads II, III and aV_F. These complications converted spontaneously after a few minutes. No cases of procedure-related death or TE were observed during hospitalization. Minor adverse events, including chest discomfort (11%), palpitations (25%) and dyspnea (1%) were reported within 1 month of the procedure. These symptoms had disappeared in most patients by 6-month follow-up. One patient had a new occurrence of migraine at 27 months after the implantation. Within a median follow-up of 49±8 months, no residual shunt of the atrial level was identified and correct positioning of the device was confirmed on transthoracic echocardiography in all patients. No death related to any cause or recurrent TE were recorded. Conclusions: Transcatheter PFO closure is a minimally invasive procedure with a high success rate, low complication rate and an excellent long-term outcome, and appears to be a wise approach for secondary prevention of recurrent embolic events in symptomatic patients. (Circ J 2011; 75: 1867-1871)

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Background: In recent years, some experimental and clinical studies on transcatheter aortic valve implantation (TAVI) have been conducted. TAVI is indicated in patients with calcified pure or predominant aortic stenosis. The risk of this technique is still high. Aortic valved stent implantation above the coronary ostia might avoid blocking the coronary ostia. Methods and Results: Twenty healthy dogs were selected to establish a canine model of acute aortic valve rupture. The dogs were randomly divided into 2 groups: the rupture model group without any treatment and the valved stent group with percutaneous valved stent implantation above the coronary ostia. The 2 groups of animals were followed up for 3 months. Echocardiography and other tests were performed to assess aortic regurgitation and ventricular function. Acute aortic valve rupture models were successfully established in 16 of 20 dogs. In the rupture model group, the mean aortic regurgitation was 6.8±1.9ml/s; only 3 of 8 animals survived for 3 months. In the valved stent group, the mean aortic regurgitation was 7.0±2.1ml/s; valved stents were successfully implanted in 8 animals. Instant post-implantation anatomy showed that the stents were located appropriately. Seven dogs survived for 3 months. Conclusions: Percutaneous valved stent implantation above the coronary ostia is feasible and effective as a transitional treatment for acute aortic valve rupture. (Circ J 2011; 75: 1872-1877)

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Background: A tortuous lesion with hinge motion is reportedly a risk factor for in-stent restenosis (ISR) after bare metal stent implantation. Sirolimus-eluting stents (SESs) implantation has dramatically reduced ISR. However, SES is a closed-cell design stent, which has low conformability and flexibility. Several studies have reported a relationship between tortuous lesions and stent fracture, which is one of the causes of ISR. The efficacy of SES in a tortuous lesion with hinge motion has not been fully evaluated. The aim of this study was to investigate the relationship between tortuous lesions and ISR after SES implantation. Methods and Results: Three year clinical follow-up data after SES implantation, including 6-9 month scheduled follow-up coronary angiography in 399 consecutive patients with 537 lesions, were obtained. Δangle was defined as the difference in the angle of the target lesion between the diastole and systole before the procedure. The incidence of ISR was 8.2%. The mean maximal angle and Δangle were larger in the ISR group (47±22° vs. 37±21°, P=0.004 and 20±13° vs. 13±10°, P<0.0001, respectively). Independent predictors of ISR were Δangle, hemodialysis, aortic ostium stenting, and diabetes mellitus. Hinge motion-associated ISR (Δangle ≥16°) occurred in 28 lesions: stent fracture in 9, stent recoil in 6, edge injury in 10, and others in 3. Conclusions: The amount of hinge motion in tortuous lesions should be considered in the selection of drug eluting stent types. (Circ J 2011; 75: 1878-1884)

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Background: Whether limb ischemic preconditioning (LIPC) is beneficial for patients undergoing mitral valve replacement (MVR) surgery is unknown. Methods and Results: Seventy-five adult patients undergoing MVR surgery were randomly assigned to 3 groups: control group (n=25), LIPC group I (3×5-min cycles of right upper arm ischemia and 5-min reperfusion; n=25) and LIPC group II (3×5-min cycles of right upper arm ischemia and 5-min reperfusion combined with 2×10-min cycles of right upper leg ischemia and 10-min reperfusion; n=25). Cardiopulmonary bypass (CPB) time, cross-clamp time, cardiac index, cumulative postoperative dosage of dobutamine, intensive care stay, postoperative hospital stay were not statistically different. Although the cumulative postoperative dosage of dobutamine was not different, there was a significantly lower inotropic requirement in LIPC II compared with the control group at 4 and 8h after surgery. Plasma levels of cardiac troponin-I in the 3 groups significantly increased during CPB and peaked at 4h after surgery. Levels of cTnI in LIPC II were significantly lower than in the control group at each time point after surgery. Conclusions: Myocardial injury is obvious after MVR surgery. LIPC can protect the myocardium from ischemia-reperfusion injury and decrease the inotropic requirement after surgery. The data also confirmed the requirement for the preconditioning stimulus to cross a threshold. (Circ J 2011; 75: 1885-1889)

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Background: Blood pressure (BP) is a strong determinant of cardiovascular diseases (CVD). The strength of this association in 2 Japanese communities with different intakes of fish was investigated. Methods and Results: The analysis was carried out in the Japanese cohorts of the Seven Countries Study (Tanushimaru and Ushibuka), which were followed for 40 years. We included 1,006 subjects for whom data on baseline BP and relevant potential confounders were available. Data were analysed using multivariable Cox proportional hazard models. In Tanushimaru men, the systolic BP level was strongly directly related to risk of stroke and CVD mortality, with hazard ratios (HR) of 4.42 (2.02-9.70) for stroke and 3.05 (1.73-3.25) for CVD for BP levels ≥140mmHg compared to <120mmHg. In Ushibuka, the HR were 1.74 (0.91-3.32) for stroke mortality and 1.66 (1.01-2.75) for CVD mortality for high vs. low systolic BP. With regard to diastolic BP, the associations with stroke and CVD mortality were similar in Tanushimaru and Ushibuka subjects. Conclusions: This study showed that the well-known relationship of systolic BP with stroke and CVD mortality was more pronounced in the Japanese farming community than in the fishing community. This brings up the hypothesis that the detrimental effect of raised systolic BP could be attenuated by a high intake of fish. (Circ J 2011; 75: 1890-1896)

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Background: The aim of the present study was to interpret B-type natriuretic peptide (BNP) level in outpatients with stable chronic heart failure (CHF); it is important to clarify whether the change in BNP represents disease progression or a range of biological variation. Methods and Results: To compare biological variation in BNP and biological variation in factors of the renin-angiotensin-aldosterone system (RAS) in stable CHF patients with dilated cardiomyopathy (DCM), the BNP plasma levels and RAS factors were measured in 115 stable outpatients with DCM. According to stepwise multivariate analysis, plasma BNP at baseline (P=0.005), presence of atrial fibrillation (P=0.015), and a high biological variation in plasma renin concentration (PRC; P=0.002) were significant independent dominant factors related to a high biological variation in BNP. Although there was no change in body weight or blood pressure during the 2-month study period, the % change in hematocrit was negatively correlated with % change in BNP (r=-0.327, P=0.0008), and positively correlated with % change in PRC (r=0.671, P=0.001). Conclusions: There was a significant relationship between biological variation in BNP and biological variation in PRC, suggesting that the physiological interaction between the natriuretic peptide system and RAS may contribute to the biological variation in plasma BNP in stable outpatients with DCM. (Circ J 2011; 75: 1897-1904)

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Background: The aim of the present study was to assess semi-quantification of myocardial perfusion using adenosine triphosphate (ATP)-stress myocardial perfusion computed tomography (MPCT) in patients with coronary artery disease (CAD).Methods and Results: Seventeen patients with CAD underwent ATP-stress MPCT, stress myocardial perfusion scintigraphy (MPS) and coronary angiography (CAG). With ATP loading (0.16mg·kg^-1·min^-1, 5min) and slow infusion of contrast medium (2ml/s, 100ml), stress images were acquired using prospective electrocardiogram-gated 64-slice CT. Stress MPCT images were analyzed according to the transmural perfusion gradient (TMPG; difference between subendocardial and epicardial attenuation, divided by wall thickness; Hounsfield units [HU]/mm) per segment, and summed TMPG was compared with those of stress MPS and CAG per territory and patient, respectively. There were 36 CAG-proved stenotic vessels in 51 (17×3) territories. There were significant correlations between TMPG and MPS stress score per segment, per territory and per patient, respectively (P<0.05). Summed TMPG in territories with and without >70% coronary stenosis was 32.3HU/mm (-1.9~90.9) and 14.5HU/mm (-5.6~38.4; P<0.05). For detecting coronary artery stenosis, sensitivity, specificity, positive and negative predictive values using the summed TMPG were 72%, 87%, 93% and 57%, in comparison with summed MPS (64%, 73%, 85%, and 46%).Conclusions: Semi-quantification of myocardial perfusion using TMPG has great potential to evaluate the severity of myocardial ischemia, similarly to MPS score. (Circ J 2011; 75: 1905-1912)

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Background: Glistening yellow coronary plaques (GY) seen on angioscopy are considered vulnerable to disruption. Collagen fiber (CF) is the main substance that protects coronary plaques against mechanical stress. Therefore, whether angioscopically defined vulnerable plaques correlate with those defined histologically was investigated. Methods and Results: One hundred and thirty-two excised human coronary plaques were classified by angioscopy into 19 GY, 49 non-glistening yellow plaques (non-GY) and 64 white plaques, and their relation to CF density was examined. CF-dense (>15/100μm), CF-loose (>5 and <15/100μm), and CF-scanty (<5/100μm) plaques were hypothesized to be stable, relatively stable, and vulnerable, respectively. Histologically the plaques were classified into non-lipid deposition, superficial lipid deposition and diffuse lipid deposition groups; the diffuse lipid deposition group was classified into necrotic core (NC) and non-NC types. Nineteen GY were composed of 4 with superficial lipid deposition, 4 with non-NC type of diffuse lipid deposition, and 11 with NC type. Sixteen (84%) of these were CF scanty. Forty-nine (100%) of non-GY and 57 (89%) of white plaques were CF dense or CF loose The sensitivity, specificity and predictive value of GY in detecting histologically vulnerable plaques were 90%, 97% and 84%, respectively, indicating that GY represented histologically vulnerable plaques. Conclusions: These pathohistological characteristics might indicate that GY, less-protected plaques against mechanical stress, are vulnerable plaques. (Circ J 2011; 75: 1913-1919)

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Background: Thrombosis occurs in the left ventricle and causes ischemic cerebral attacks. However, differences in the incidence of left ventricular thrombi (LVT) among various categories of heart diseases are not known. Methods and Results: From April 2000 to 31 March 2008, 258 patients (104 females and 154 males; age 63±6 years) with a heart disease underwent cardioscopy of the left ventricle. LVT were detected by cardioscopy in 78 of 258 patients; 12.5% of 57 patients with stable angina, 0% of 9 with unstable angina, 45.2% of 42 with acute myocardial infarction, 23.2% of 43 with old myocardial infarction, 61.9% of 21 with idiopathic acute myocarditis, 44.3% of 68 with idiopathic chronic myocarditis, 33.3% of 6 with rheumatic valvular disease, 25.7% of 31 with idiopathic dilated cardiomyopathy and in 8.0% of 12 with idiopathic hypertrophic cardiomyopathy. Nine of 78 thrombi were globular and 69 were mural. The detection rate of LVT by cardioscopy, left venticulography, non-contrast and contrast echocardiography was 30.2%, 2.7%, 1.9% and 7.0%, respectively. Conclusions: LVT were frequently detected by cardioscopy in patients with heart diseases. Although invasive, cardioscopy was more sensitive in detecting LVT than left ventriculography, and non-contrast and contrast echocardiography. (Circ J 2011; 75: 1920-1926)

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Background: Clinical importance of hyponatremia in ST-elevation acute myocardial infarction (STEMI) in the era of primary intervention has not been fully understood. The aim of this study was to investigate the impact of hyponatremia on outcomes in patients with STEMI and secondarily to investigate the contribution of arginine vasopressin (AVP) to hyponatremia in STEMI. Methods and Results: Hyponatremia was defined as a sodium concentration <136mmol/L at 72h after hospitalization. First, the short-term (in-hospital mortality or congestive heart failure (CHF)) and long-term prognosis (cardiac death, re-admission for CHF) in STEMI patients was conducted. Second, the relationship between serum sodium level and plasma AVP was investigated. In hyponatremic patients the incidence of in-hospital heart failure was significantly greater (P=0.0018), long-term cardiac death was a higher trend (17.2% vs. 6.3%, P=0.19) and re-admission due to CHF was significantly more frequent (20.7% vs. 4.5%, P=0.0024). Plasma AVP level was higher in the hyponatremia group (4.5 vs. 2.7pg/ml, P=0.003), and it had a negative correlation with serum sodium level (r=-0.28, P=0.02). Conclusions: Hyponatremia was frequently found in the early phase of STEMI, and associated with heart failure in both short- and long-term outcomes. Non-osmotic secretion of AVP could be involved in hyponatremia in STEMI patients. (Circ J 2011; 75: 1927-1933)

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Background: The early diagnosis of myocardial ischemia is still challenging. The aim of the present study was to determine whether subendocardial hypokinesis and post-systolic contraction could be early markers of myocardial ischemia. Methods and Results: Thirty-one consecutive patients with flow-limiting severe coronary stenosis but without visually abnormal left ventricular wall motion underwent quantitative echocardiography. Myocardial strain was measured using layer-by-layer analysis in severely hypoperfused segments. Radial strain (RS) was measured in the subendocardial, subepicardial, and total wall (innerRS, outerRS, and totalRS, respectively). Circumferential strain (CS) was also measured as 3 separate layers: subendocardial, mid-layer, and subepicardial layers (innerCS, midCS, and outerCS, respectively). Post-systolic shortening (PSS) was defined as the peak strain after end systole, and post-systolic strain index (PSI) was calculated as PSS divided by end-systolic strain. TotalRS was similar between ischemic and normally perfused segments, but innerRS and inner/outer RS ratio were significantly smaller in the ischemic segments than in corresponding segments in healthy subjects. Receiver operating characteristic analysis identified an optimum cut-off for PSI of 0.6. The combined criteria of inner/outer RS ratio <1.0 and PSI >0.6 achieved 95% specificity for the presence of flow-limiting stenosis. Conclusions: Combined assessment of both subendocardial contractile impairment and PSS is very useful in identifying a severely hypoperfused left ventricular wall even without visual wall motion abnormality. (Circ J 2011; 75: 1934-1941)

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Background: Although E/e' (the ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity) is widely used to measure left ventricular filling pressure (LVFP), its accuracy is questionable in coronary artery disease patients. Methods and Results: Echocardiograms and LVFP were obtained from 174 patients with stable angina (Canadian Cardiovascular Society angina grade I-II) who had received interventions for angiography-confirmed coronary stenosis. Compared with single-vessel groups, the multiple-vessel group exhibited lower mitral annular velocities, higher LVFP, and stronger correlations between E/regional e' and LVFP. Additionally, stronger correlations between E/regional e' and LVFP existed in patients with systolic dysfunction or lower variation of myocardial performance index (MPI) among anterior, inferior and lateral borders of mitral annulus. Average e' was not superior to any regional e' for assessing LVFP by the E/e' method. E/e' and left atrial (LA) ejection fraction (EF) correlated linearly with LVFP, but the correlation between LA distensibility and LVFP was logarithmical. Compared with E/e', LA distensibility and LAEF were superior for identifying high LVFP. Conclusions: E/e' is not completely satisfactory for assessing LVFP in patients with stable angina, especially those with single-vessel disease, preserved systolic function or high MPI variation. For identifying high LVFP, LA distensibility and LAEF are better than E/e'. (Circ J 2011; 75: 1942-1950)

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Background: Although statins vary in their effectiveness in lowering low-density lipoprotein cholesterol (LDL-C) and increasing high-density lipoprotein cholesterol (HDL-C) levels, there is little evidence that the degree of these changes can explain cardiac risk reduction in Japan. Our objective was to compare the efficacy of statins on serum lipid levels and to explore the association between those changes and cardiac events in patients after percutaneous coronary intervention (PCI). Methods and Results: The 743 consecutive patients who underwent PCI from 2001 to 2008 were retrospectively investigated. Treatment with either atorvastatin or pitavastatin significantly reduced LDL-C compared with pravastatin or no statin. In contrast, only pitavastatin treatment significantly increased HDL-C (13.4±22.9%, P=0.01 vs. no statin). Each statin significantly prevented major adverse cardiac events (MACE) compared with no statin, and pitavastatin was the most effective of all. Multivariate-adjusted analysis revealed that percent changes of both LDL-C and HDL-C independently predicted the incidence of MACE (hazard ratio [HR]: 1.015; 95% confidence interval [CI]: 1.010-1.020, HR: 0.988; 95%CI: 0.981-0.996, respectively). This relationship was preserved in patients with a baseline HDL-C level ≤45mg/dl, but not HDL-C level >45mg/ml. Conclusions: The extent of changes in LDL-C and HDL-C with statin treatment would independently alter the risk of cardiac events in Japanese patients for secondary prevention. Statins with varying lipid-modifying ability might provide differing prognosis in patients after PCI. (Circ J 2011; 75: 1951-1959)

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Background: A high low-density lipoprotein cholesterol (LDL-C) to a high-density lipoprotein cholesterol (HDL-C) ratio is associated with cardiac events, while the left main coronary artery (LMCA) is considered to be an important target of atherosclerotic plaque accumulation. This aim of the present study was to investigate the relationship between a LDL-C/HDL-C ratio and the characteristics of tissue components of LMCA plaque. Methods and Results: One-hundred-twenty consecutive patients with stable angina pectoris who received chronic statin treatment underwent percutaneous coronary intervention for the left coronary artery. We prospectively performed integrated backscatter (IB) intravascular ultrasound (IVUS) to their LMCAs and evaluated the tissue characteristics. According to the median value of their LDL-C/HDL-C ratios (2.4), they were divided into 2 groups [high LDL-C/HDL-C ratio (>2.4) (n=60) or low LDL-C/HDL-C ratio (≤2.4) (n=60)]. There was no significant difference in the data analyzed using conventional IVUS between the 2 groups. In the IB-IVUS analysis, patients with a high LDL-C/HDL-C ratio had a larger lipid volume and a smaller fibrous volume compared to patients with a low LDL-C/HDL-C ratio (52±10% vs. 48±10%, P=0.014 and 45±9% vs. 50±10%, P=0.010). Conclusions: A high LDL-C/HDL-C ratio was associated with a high percentage of lipid volume and a low percentage of fibrous volume in LMCA lesions. Our findings might well suggest the increased risk of cardiovascular events in patients with a high LDL-C/HDL-C ratio. (Circ J 2011; 75: 1960-1967)

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Background: Pioglitazone (PIO) is a new class of anti-diabetic agent with an anti-inflammatory effect. In the experimental studies, pretreatment with PIO before ischemia/reperfusion reduced ischemia-reperfusion injury and myocardial infarct size. However, the clinical efficacy of this therapy in patients with acute myocardial infarction (AMI) remains unknown. Methods and Results: Three hundred and nineteen diabetic patients with ST-segment elevation AMI, treated with bare metal stent within 24h from the onset of AMI were examined. Myocardial blush grade, ST-segment resolution, peak creatine kinase (CK) level, and left ventricular ejection fraction (LVEF) were compared between PIO group (pretreatment with PIO [+]; n=26) and non-PIO group (pretreatment with PIO [-]; n=293). The PIO group showed a significantly higher incidence of blush score ≥2 and complete ST-segment resolution (blush score ≥2; 38% vs. 71%, P=0.04, ST-segment resolution; 44% vs. 71%, P=0.04). Besides, slow flow/no-reflow phenomenon and reperfusion arrhythmia did not occur in this group. Better improvement of LVEF and lower peak CK level was observed in this group, although these were not statistically significant (LVEF 48% vs. 41%, P=0.10, peak CK level 2,041 vs. 3,207, P=0.06). Conclusions: Pretreatment with PIO in diabetic patients with AMI resulted in better myocardial perfusion with less reperfusion injury. (Circ J 2011; 75: 1968-1974)

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Background: There has been no nationwide survey concerning peripartum cardiomyopathy (PPCM) among the Asian population, and clinical profiles of PPCM complicated with hypertensive disorders complicating pregnancy (HD) as the major risk factor of PPCM have not been characterized. Methods and Results: A retrospective, nationwide survey of PPCM in 2007 and 2008 all over Japan was performed and the clinical characteristics were compared between patients with and without HD. We obtained data for 102 patients. HD during pregnancy occurred in 42 patients (41%). Patients with HD were older than those without HD (33.8 vs. 31.9 years old, P<0.05) and babies were delivered more frequently by Caesarean section (81% vs. 52%, P<0.01). Although cardiac parameters at diagnosis were similar in patients with and without HD, patients with HD were hospitalized for a shorter period and had better cardiac function after 7 months. Multivariate regression analysis revealed that HD was independently associated with a shorter hospital stay and a higher left ventricular ejection fraction at last follow up. Conclusions: PPCM complicated with HD had different clinical characteristics from those without HD. This condition might be a unique subset of PPCM that is characterized by relatively swift recovery except in the cases of death. In order to prevent severe heart failure and maternal death, peripartum women should be treated with HD cautiously and must immediately undergo a cardiac examination as needed. (Circ J 2011; 75: 1975-1981)

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Background: Although some β-blockers are effective for patients after acute myocardial infarction (AMI), few studies have compared their additive effects on renin-angiotensin system inhibitors (RAS-Is). Methods and Results: The 251 consecutive AMI patients administered angiotensin-converting-enzyme inhibitors (ACE-Is) or angiotensin-II receptor blockers (ARBs) were retrospectively investigated and divided into 2 groups: treated without β-blockers (no-β-blocker group, n=80) or treated with β-blockers before discharge (β-blocker group, n=171; carvedilol [n=91] or bisoprolol [n=80]). The doses of RAS-Is used for patients in the no-β-blocker group were at least double those used in the β-blocker group. No significant differences between the 2 groups were observed with regard to baseline characteristics. After a 12-month follow-up, the survival and cardiac event-free rates in the β-blocker group were significantly higher than those in the no-β-blocker group. The percent change in blood pressure did not significantly differ between the 2 groups, but the levels of brain natriuretic peptide, metalloproteinase-2, and metalloproteinase-9 and the left ventricular ejection fraction improved significantly in the β-blocker group compared with the no-β-blocker group. Regarding the 2 β-blockers, carvedilol treatment produced more favorable outcomes than bisoprolol. Conclusions: The data suggest that treatment with RAS-I in combination with β-blocker is more effective for patients after AMI than treatment with RAS-I alone. (Circ J 2011; 75: 1982-1991)

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Background: Serum heart-type fatty acid-binding protein (H-FABP) is widely applied as a marker of cardiac myocyte injury. Recently, it has been reported that levels of H-FABP are elevated in adult patients with chronic heart failure and thus provide useful prognostic information. The aim of the present study was to examine the relationships between serum H-FABP levels and pathophysiological characteristics in children and adolescents with congenital heart disease (CHD). Methods and Results: Serum H-FABP levels were preoperatively and postoperatively measured in 238 consecutive patients with CHD aged 1-31 years. The relationships between H-FABP levels and severity of heart failure, circulatory status and laboratory data were cross-sectionally analyzed. Multivariate regression analysis indicated that serum H-FABP levels are independently affected by age, New York Heart Association functional class, creatine kinase MB, creatinine and arterial oxygen saturation (standard regression coefficients, -0.378, 0.237, 0.422, 0.615, and -0.210, respectively). Neither left ventricular ejection fraction nor B-type natriuretic peptide correlated with H-FABP levels. Conclusions: H-FABP could serve as a new monitoring tool to provide information that will guide the optimal therapy and management of CHD patients. (Circ J 2011; 75: 1992-1997)

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Background: The epidemiology of symptomatic venous thromboembolism (VTE) in Taiwan has not been well investigated. The aim of this study was to report on the epidemiology and short-term prognosis of symptomatic VTE. Methods and Results: This nationwide population-based cohort study used the Taiwanese National Health Insurance claims databases to identify adults older than 18 years of age with symptomatic VTE diagnosed in 2002. We investigated the clinical features of VTE and determined independent risk factors of 1-month mortality. A total of 2,774 patients were identified with a mean age of 62.8 years and the female-to-male ratio was 1.15:1. The crude incidence of symptomatic VTE was 16.5 per 100,000 persons, which steadily increased with age, ranging from 4 per 100,000 in patients <40 years old to 108 per 100,000 in patients ≥80 years. We observed no seasonal and meteorological variations in the incidence of VTE. The overall 1-month mortality rate was 8.8%, with 7.1% in deep venous thrombosis and 12.9% in pulmonary embolism. Multivariate analysis demonstrated that pulmonary embolism, cancer, neurologic disease with extremity paresis or paralysis, older age, longer hospital stay, and major abdominal and thoracic surgery in the 3 months preceding VTE were independent predictors of 1-month death. Conclusions: Although the incidence of VTE was lower in Taiwanese populations than in Western ones, short-term mortality rates were high in specific populations. These findings suggest optimal treatment is needed in higher-risk patients. (Circ J 2011; 75: 1998-2004)

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Background: The role of adiponectin (APN), an adipose tissue-specific secretory protein, on chronic rejection after cardiac transplantation in APN-sense transgenic mice (APN-SE) was evaluated. Methods and Results: Heterotopic cardiac transplantation in major histocompatibility complex class II-mismatched mice was performed. B6.C-H-2^bm12KhEg (Bm12) hearts were transplanted into APN-SE, and allografts were harvested at 8 weeks after transplantation. Quantitative polymerase chain reaction (PCR) and immunohistochemical staining showed that the expression of both AdipoR1 and AdipoR2 was induced in APN-SE recipients. Neointimal hyperplasia was significantly decreased in allografts transplanted into APN-SE (luminal occlusion, 8.9±2.2%) compared to those transplanted into controls (49.4±10.5%; P=0.011). APN-SE showed significantly reduced mRNA levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-6, and monocyte chemoattractant protein-1 (MCP-1) by quantitative PCR. Western blot analysis revealed that the protein levels of IFN-γ and MCP-1 were reduced in APN-SE recipients. Proliferation of smooth muscle cells stimulated with activated T cells was suppressed by APN addition, and this effect was canceled by treatment with an adenosine monophosphate-activated protein kinase (AMPK) inhibitor. Conclusions: APN plays a critical role in the attenuation of chronic rejection by suppressing inflammatory cytokine and chemokine expression and enhancing APN receptor expression. APN plays a beneficial role in reducing the progression of cardiac allograft vasculopathy through the AMPK pathway. (Circ J 2011; 75: 2005-2012)

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Predicting the occurrence of acute coronary syndrome (ACS) is a major clinical challenge for cardiologists. Multi-slice computed tomography (CT) has enabled easy detection and assessment of atherosclerotic coronary plaque, and therefore has considerable potential in the prevention of ACS. The recent development of 64-slice cardiac CT enables detailed information on both plaque properties and characteristics to be obtained with excellent diagnostic accuracy. Cardiac CT therefore has great potential for detecting the unstable plaques that are prone to result in ACS. (Circ J 2011; 75: 2013-2018)

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Predicting acute cardiovascular ischemic events is a crucial and urgent issue in the current cardiovascular field. An enormous effort to develop methodologies to achieve this purpose is being undertaken in cardiovascular institutes worldwide. However, currently, there is no established method of determining acute cardiovascular ischemic events in advance. This article reviews the latest progress on understanding how these events occur and how they can be detected. This goal represents a great dream that has realistic expectations. (Circ J 2011; 75: 2019-2026)

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