Fully bioabsorbable scaffolds (BRS) are a novel approach that provides transient vessel support with drug delivery capability without the long-term limitations of the metallic drug-eluting stents (DES), such as permanent caging with or without malapposition. The technology has the potential to overcome many of the safety concerns associated with metallic DES, and possibly even convey further clinical benefit. Although the technology is still in its infancy, several devices have been tested in clinical trials and the initial results have been very promising. This review will discuss the emerging need for BRS, the theoretical advantages of this new technology over current generation metallic DES and review the status of the currently available BRS. In addition, we will discuss the ideal duration of bioresorption, the proven and potential clinical benefits and future perspectives of this rapidly progressing technology. (Circ J 2011; 75: 509-520)

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A variable proportion of cardiac resynchronization therapy (CRT) patients do not benefit from treatment (termed `non-responders'). The problem of non-response to CRT might become increasingly important, because it is anticipated that larger groups of heart failure patients are indicated to the therapy. This article will discuss the definition of response to CRT, the parameters related to response to CRT, and finally whether response to CRT might be predicted. The effort to improve patient selection in order to maximize human and financial resource utilization has fallen short so far. It is, however, conceivable that rather than the identification of a `universally' applicable cut-off value, risk strata-in which inclusion of method for determination of left ventricular volumes, etiology, QRS duration and morphology, etc-might better serve the goal of defining non-responders. Potentially simple clinical scores might help in refining outcome and by doing so, allow to more precisely measure response to CRT in daily practice in the individual patient at the time of CRT implantation. Although sophisticated cardiac imaging modalities have been intensively utilized for improving patient outcome, it seems that many mechanical dyssynchrony measures suffer from technical limitations and from difficult interpretation of the complex signals, which lack reproducibility outside highly specialized laboratories. (Circ J 2011; 75: 521-527)

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Peroxisome proliferator-activated receptor-γ (PPARγ) is a member of the ligand-activated nuclear receptor family. Thiazolidinediones, such as rosiglitazone and pioglitazone, are synthetic agonists selective for PPARγ and have been used in the clinical treatment of type 2 diabetes. However, beyond the metabolic effects on glycemic control, PPARγ and its ligands also have profound effects on cardiovascular biological and pathophysiological processes. As cardiovascular diseases are closely associated with insulin resistance, and the major cause of death and complications of type 2 diabetes, a comprehensive understanding of the cardiovascular roles of this receptor is critical for the rational application of the existing agonists and the future development of therapeutic modulators. Therefore, this review will focus on the recent advances regarding the cardiovascular functions of PPARγ and its recognized effects on major cardiovascular diseases, in particular, atherosclerosis and associated processes. (Circ J 2011; 75: 528-535)

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Background: The Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (POSSUM), which consists of a physiological score (PS) and an operative severity score, is useful in determining the risk profile for patients with abdominal aortic aneurysms in Western countries, but no information is available on the use of this method in Japan. Methods and Results: A retrospective cohort study involving 225 patients was performed, and the prognostic factors for morbidity and in-hospital mortality including POSSUM were investigated. The morbidity rate was 26%. On univariate analysis age, renal disease, hemoglobin, albumin, operation time, blood loss and PS were significantly different. On multivariate analysis PS was significantly different. Using receiver operating characteristic (ROC) analysis, PS had an area under the curve (AUC) of 0.712 and the best cut-off point was 18. The in-hospital mortality rate was 2.2%. On univariate analysis renal disease, albumin and PS were significantly different, and on multivariate analysis PS was significantly different. On ROC analysis PS had an AUC of 0.921 and the best cut-off point was 22. Conclusions: PS was the only independent risk factor for morbidity and in-hospital mortality. Further studies may be required to develop a risk-scoring system. (Circ J 2011; 75: 550-556)

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Background: The degree of electroanatomical remodeling of the left atrial (LA) affects the clinical outcome after rhythm control of atrial fibrillation (AF). Our hypothesis was that plasma concentrations of transforming growth factor (TGF)-β and tissue inhibitor of metalloproteinase (TIMP)-1 reflect LA voltage and structural remodeling in patients with non-valvular AF. Methods and Results: In the study, 242 patients (male 79.4%, 55.1±11.0 years old) with AF (155 paroxysmal AF, 87 persistent AF) underwent catheter ablation. Pre-ablation plasma concentrations of TGF-β and TIMP-1 and the degree of electroanatomical remodeling quantified by LA voltage map (NavX) and 3D-CT were evaluated. The mean LA voltage and volume were compared in patients with high TGF-β (≥10.0ng/ml, H-TGF) vs. low TGF-β (<10.0ng/ml, L-TGF) and high TIMP-1 (≥1.1ng/ml, H-TIMP) vs. low TIMP-1 (<1.1ng/ml, L-TIMP). Patients with H-TGF had lower mean LA voltage (P=0.014) and greater LA volume (P=0.022), particularly, posterior venous LA volume (P=0.005) than those with L-TGF. In patients with H-TIMP, the mean LA voltage (P=0.019) was lower than those with L-TIMP. LA volume was significantly higher (P<0.001) in patients with ejection fraction ≤58% than those with >58%. Conclusions: In patients with non-valvular AF, high plasma concentrations TGF-β and TIMP-1 and low ejection fraction were closely related with electroanatomical remodeling of LA. (Circ J 2011; 75: 557-564)

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Background: Ablation of ventricular tachycardia originating from the interventricular septum (IVS) is often limited by the presence of re-entrant pathways deep in the IVS. We compared the efficacy of bipolar ablation vs. sequential unipolar ablation in creating a transmural lesion across the porcine IVS. Methods and Results: Seventeen excised swine hearts were superfused by pulsatile saline flow. Bipolar ablation (at 30W, 50W or 70W for 120s) was performed between 2 saline-irrigated (20ml/min) 4-mm tip electrodes, 1 on the left and 1 on the right side of the IVS. Sequential unipolar ablation (at 30W, 50W or 70W for 120s) was performed on the left and right sides of the IVS with an irrigated-tip catheter. Bipolar ablation produced a narrower, deeper lesion than did unipolar ablation. A transmural lesion was created by sequential unipolar ablation in 7.7%, 8.3% and 0% of tissue preparations and by bipolar ablation in 50.0%, 46.7% and 71.4% of tissue preparations at 30W, 50W and 70W. Conclusions: Bipolar ablation of the IVS was highly effective for creating a transmural IVS lesion. (Circ J 2011; 75: 565-570)

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Background: Long-term effects of restrictive mitral annuloplasty (RMA), especially on hemodynamics and left ventricular (LV) function in patients with functional mitral regurgitation (MR), have not been fully investigated. Methods and Results: From 1999 to 2008, 44 patients with refractory heart failure and functional MR underwent RMA with stringent downsizing of the mitral annulus. Serial echocardiography was performed to evaluate LV function (reverse remodeling), estimated systolic pulmonary artery pressure (PAP) and mitral valve geometry at baseline and at discharge, and annually thereafter. Cardiac catheterization was performed at baseline, and at discharge to evaluate acute hemodynamic change. There were 3 early deaths, and the 5-year survival rate was 78±8%. In 41 survivors the clinical symptoms, stratified according to New York Heart Association class, significantly improved after surgery. Postoperative cardiac catheterization showed significant unloading for left ventricle, as well as improvement in LV systolic function. Serial echocardiography showed that improvements in LV function and systolic PAP were sustained in the majority of patients. Multivariate Cox regression analysis identified preoperative pulmonary hypertension (systolic PAP>60mmHg) as the significant predictor for postoperative adverse cardiac events. Conclusions: RMA for functional MR resulted in sustained improvement of hemodynamics and LV function over time. Additional studies are needed to define the negative impact of preoperative pulmonary hypertension in patients with this condition. (Circ J 2011; 75: 571-579)

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Background: The 2005 guidelines for cardiopulmonary resuscitation (CPR) have recommended that administration of atropine can be considered for non-shockable rhythm, but there are insufficient data in humans. Methods and Results: The effects of atropine were assessed in 7,448 adults with non-shockable rhythm from the SOS-KANTO study. The primary endpoint was a 30-day favorable neurological outcome after cardiac arrest. In the 6,419 adults with asystole, the epinephrine with atropine group (n=1,378) had a significantly higher return of spontaneous circulation (ROSC) rate than the epinephrine alone group (n=5,048) with an adjusted odds ratio of 1.6 (95% confidence interval (CI) 1.4-1.7, P<0.0001), but the 2 groups had similar 30-day favorable neurological outcome with an adjusted odds ratio of 0.6 (95%CI 0.2-1.7; P=0.37). In the 1,029 adults with pulseless electrical activity (PEA), the 2 groups had similar rates of ROSC and 30-day favorable neurological outcome, and the epinephrine with atropine group had a significantly lower 30-day survival rate than the epinephrine alone group with an adjusted odds ratio of 0.4 (95%CI 0.2-0.9, P=0.016). Conclusions: Administration of atropine had no long-term neurological benefit in adults with out-of-hospital cardiac arrest due to non-shockable rhythm. Atropine is not useful for adults with PEA. (Circ J 2011; 75: 580-588)

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Background: It is known that HMG-CoA reductase inhibitors (statins) may have a therapeutic benefit in patients with heart failure (HF). However, no studies have yet evaluated the possible interaction of statins and angiotensin-II receptor blockers (ARBs) on left ventricular (LV) function in patients with HF. We hypothesized that statins might alter the effect of ARBs on cardiac function in patients with HF. Methods and Results: We prospectively randomized patients with chronic HF who received the ARB, losartan (LOS group), or the statin, simvastatin (SIM), in combination with LOS (SIM+LOS group) at our hospitals and assessed before and after treatment for 6 months. Although no significant improvement of HF symptoms as evaluated by the New York Heart Association (NYHA) classification was observed in the LOS group, HF symptoms in the SIM+LOS group significantly improved. The percent increase of LV ejection fraction after treatment in the SIM+LOS group was significantly larger than in the LOS group. Furthermore, the plasma brain natriuretic peptide level was significantly lower after treatment in the SIM+LOS group than in the LOS group. Conclusions: Combined statin and ARB therapy significantly improves both symptoms and LV function over time in patients with HF. Thus, the combination of an ARB with a statin may be a useful therapeutic strategy for HF. (Circ J 2011; 75: 589-595)

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Background: Systolic abnormality, as well as diastolic dysfunction, is observed in patients with heart failure with preserved ejection fraction (HFPEF). However, the role of these 2 conditions in the transition from asymptomatic diastolic dysfunction to symptomatic heart failure remains unclear. We recently demonstrated that diastolic wall strain (DWS) inversely correlates to the myocardial stiffness constant. Methods and Results: This study consisted of 127 subjects: 52 consecutive HFPEF patients (HFPEF group), 50 asymptomatic hypertensive patients with ejection fraction ≥50% whose age, gender and left ventricular (LV) mass index matched those of the HFPEF group (HT group) and 25 normal volunteers (Normal group). The tissue Doppler-derived peak systolic and early diastolic velocities of the mitral annulus were significantly decreased in groups HFPEF and HT than in group Normal, but were not significantly different between groups HFPEF and HT. DWS was significantly lower in group HFPEF than in group HT. Conclusions: The transition from asymptomatic diastolic dysfunction stage to HFPEF stage is not attributed to progression of systolic abnormality, and exacerbation of LV distensibility rather than relaxation plays a crucial role in the development of HFPEF. (Circ J 2011; 75: 596-602)

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Background: Clarification of frequency and distribution of yellow plaques and disrupted plaques will increase understanding of acute coronary syndrome (ACS) onset. Methods and Results: Consecutive patients with ACS (n=75) or without ACS (n=90) who received coronary angioscopic examination were studied. Distance from ostium to yellow plaques, diameter stenosis and vessel wall irregularity at the site of yellow plaques, their yellow color grade (grade 13) and if they had thrombus were analyzed. Yellow plaques with thrombus were regarded as disrupted. Average number of yellow plaques, grade-3 yellow plaques and disrupted yellow plaques per vessel was 4.0, 0.87 and 1.0, respectively. The number of grade-3 yellow plaques and disrupted yellow plaques per vessel were larger in ACS than in non-ACS patients. Yellow plaques were distributed diffusely in the right coronary artery but more in mid-segments in the left anterior descending coronary artery and left circumflex coronary artery. Diameter stenosis in the non-culprit segments was severer at disrupted than at non-disrupted yellow plaques. Vessel wall irregularity was detected more frequently at disrupted than at non-disrupted yellow plaques. Conclusions: Approximately 4 yellow plaques, 1 grade-3 yellow plaque and 1 disrupted yellow plaque were detected per vessel. About 25% of detected yellow plaques were disrupted. More grade-3 yellow plaques and disrupted yellow plaques were detected in ACS than in non-ACS patients. These findings strengthen the association between yellow plaques detected by angioscopy and ACS events. (Circ J 2011; 75: 603-612)

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Background: In a few studies, huge anatomical variability of coronary venous system (CVS) has been documented without analysis of its variants. The aim of the present study was to evaluate anatomical variants of CVS in multislice computed tomography (MSCT). Methods and Results: In 199 patients (114 males, age 56.6±11.5 years), a 64-slice computed tomography (Aquilion 64) was performed due to coronary artery disease suspicion. A scan with electrocardiogram-gating was performed using a slice thickness of 0.5mm during a breath-hold. In each case, 3D volume rendering and 2D multi-planar reformatting reconstructions of CVS were created (Vitrea 2). As target veins for cardiac resynchronization therapy (CRT), the posterolateral, lateral and anterolateral veins were recognized. Coronary sinus was well visualized in all cases. A total of 27 anatomical variants of CVS were identified, 9 of them are most common (in 148/199 cases; 74.4%). In 4 out of these 9 variants, a single coronary vein in the target area for CRT appeared, 2 target veins in 3 variants and 3 veins in 2 variants occurred. In 6 cases (2 seldom variants-3.0%) no veins in the target area were identified. Conclusions: In the majority of the examined patients, at least one vein in the target area for CRT was observed. Anatomical variability of CVS strengthen the potential role of MSCT in CVS visualization before CRT implantation. (Circ J 2011; 75: 613-618)

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Background: To delineate the mechanism of mitral regurgitation (MR) in the acute phase of inferior wall myocardial infarction (MI). Methods and Results: In 97 patients (age 59±12 years) with acute inferior wall MI, the severity of MR, left ventricular (LV) geometric changes and function within 1.7±1.3 days after MI by echocardiography was retrospectively evaluated. Infarct size was measured within 3.9±1.7 days by cardiac magnetic resonance. Mild MR was present in 16 (16.5%) and moderate MR in 12 (12.4%) of 97 patients. There were no significant differences in mitral annular area, sphericity and distances between papillary muscle tips and the contralateral mitral annulus. However, patients with moderate MR had significantly larger LV end-systolic volume, tenting area and infarct size. There was a graded relationship between the severity of MR and LV ejection fraction. In a multivariable regression analysis, LV ejection fraction and tenting area were found to be independent predictors of the severity of MR (r²=0.180, P=0.001). Conclusions: MR was associated with LV systolic dysfunction, increase in end-systolic LV volume and tethering of mitral leaflet, suggesting reduced closing force as a consequence of LV systolic dysfunction in the presence of leaflet tethering would play a more pivotal role in the development of MR. (Circ J 2011; 75: 619-625)

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Background: In patients with acute myocardial infarction (AMI), QRS score at presentation electrocardiogram (ECG) may reflect the evolutionary stage of the infarction and allow one to predict the degree of myocardial reperfusion potentially achievable by reperfusion therapy. Methods and Results: The relationship between QRS score on admission ECG and myocardial blush grade, an angiographic marker of myocardial reperfusion, was examined in 416 patients with a first anterior AMI who received reperfusion therapy within 6h after symptom onset. Patients were classified into 3 groups according to QRS score: 0 or 1 (n=102), 2-4 (n=228), and ≥5 (n=86). Higher QRS scores were associated with a longer time to admission, a greater ST-segment elevation, a higher frequency of impaired initial and final culprit coronary vessel flow, a higher peak creatine kinase level, and a higher frequency of impaired myocardial reperfusion as defined by myocardial blush grade 0/1 on the final angiogram. Multivariate analysis showed that a high QRS score ≥5 was the strongest predictor of impaired myocardial reperfusion (odds ratio 20.3, P<0.001). These findings were similar when the data were stratified according to time to admission (≤2h, >2h). Conclusions: In patients with a first anterior AMI treated by reperfusion therapy, admission high QRS score ≥5 strongly predicts impaired myocardial reperfusion, even when presentation is early (≤2h). (Circ J 2011; 75: 626-632)

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Background: It has recently become possible to analyze coronary plaque characteristics by using integrated backscatter intravascular ultrasound (IB-IVUS). The aim of this study was to use this modality to evaluate the impact of early intervention with rosuvastatin on both the volume and tissue characteristics of non-culprit plaques in acute coronary syndrome (ACS). Methods and Results: Patients with ACS underwent IB-IVUS after percutaneous coronary intervention procedure and were administered rosuvastatin. Follow-up IB-IVUS was recorded 6 months later. We analyzed the changes in plaque burden and tissue characteristics in these patients. Plaque components were classified as calcified, fibrous, and lipid according IB-IVUS. We comprehensively analyzed 20 ACS patients. The low-density lipoprotein-cholesterol levels decreased significantly from 117±34mg/dl to 73±19mg/dl (P<0.001) after statin therapy. Comparing the baseline images with the follow-up ones revealed a significant reduction in the plaque burden from 98.4±42.1mm³/10mm to 80.2±35.8mm³/10mm (P<0.001) and in the lipid volume from 44.1±29.6mm³/10mm to 28.6±17.8mm³/10mm (P<0.001). With respect to the % lipid volume, the reduction rate at follow-up showed a significant correlation with its baseline value (r=-0.498, P=0.024). Conclusions: Early intervention with rosuvastatin in ACS patients enabled significant reduction of the non-culprit plaque during 6 months. This regression was mainly due to the decrease in the lipid component of the plaque. (Circ J 2011; 75: 633-641)

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Background: Recent development of multi-detector computed tomography (MDCT) has made the detection of myocardial bridge (MB) easier on the left anterior descending coronary artery (LAD). The LAD segment proximal to the MB is well known to be susceptible to atherosclerosis. Anatomical characteristics of MB on LAD in patients with myocardial infarction (MI) were examined by MDCT. Methods and Results: Subjects were 43 MI patients who had MB in the LAD and comprised 2 groups: 14 with culprit lesions in the LAD proximal to MB (culprit group) and 29 without culprit lesions in the LAD (non-culprit group). MB length, MB thickness, and the distance from the orifice of left main trunk (LMT) to MB entrance were compared. Age and coronary risk factors showed no significant difference between the 2 groups. MB length (P=0.011), MB thickness (P=0.035), and index of the length multiplied by thickness of MB (P=0.031) were significantly greater in the culprit group. The distance from the orifice of the LMT to MB entrance was significantly shorter in the culprit group (P=0.006). Conclusions: Anatomical properties of MB, such as length and thickness of MB as well as MB location, are associated with the formation of culprit lesions of LAD proximal to MB in MI. (Circ J 2011; 75: 642-648)

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Background: Cardiac involvement in Churg-Strauss syndrome (CSS) is not uncommon, but its frequency varies widely and may depend on the activity of the disease. Therefore, the cardiac involvement in CSS patients in clinical remission was assessed in the present study. Methods and Results: In 20 CSS patients in remission and 20 sex- and age-matched healthy controls, an ECG stress test, echocardiography, and 24-h ECG Holter monitoring were performed, together with cardiac magnetic resonance imaging (cMRI). Cardiac involvement was present in 90% (18/20) of CSS patients. Left ventricular ejection fraction (LVEF) was on average lower in the CSS group than in controls (P<0.05), with 7 patients showing systolic heart failure (LVEF <50%). cMRI changes included late gadolinium enhancement lesions in the LV in 89% of patients (17/19), present in all layers of the myocardium. Signs of ongoing inflammation (early gadolinium enhancement) and edema (T2-weighted imaging) were present in 6/19 patients. Holter monitoring revealed both supraventricular and ventricular arrhythmias more frequently in CSS patients when compared with controls (P<0.05). Absolute eosinophil count before the initiation of treatment was higher in rhythm disturbances (P<0.05), and inversely correlated with LV systolic function (rho -0.65). Conclusions: Heart involvement in CSS patients who are in clinical remission is very common. It is characterized not only by fibrosis, but also by an active inflammatory process. The latter finding might influence therapeutic decisions in CSS patients in full clinical remission. (Circ J 2011; 75: 649-655)

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Background: Cardiac troponin T (cTnT) is useful biomarker in patients with chronic heart failure (CHF). However, its clinical use is limited by the low sensitivity of the conventional commercial assay system. Recently, a highly sensitive cTnT (hs-cTnT) assay has become commercially available. Methods and Results: To compare the prognostic value of conventional cTnT and hs-cTnT in patients with nonischemic dilated cardiomyopathy (DCM), hemodynamic parameters and the serum levels of conventional cTnT, hs-cTnT and brain natriuretic peptide (BNP) were measured in 85 consecutive CHF patients with nonischemic DCM and then these patients were followed for a mean of 4.1 years. During long-term follow up, there were 20 cardiac deaths. In 85 DCM patients, conventional cTnT was elevated (≥0.03ng/ml) in 4 patients (5%) and hs-cTnT was elevated (≥0.01ng/ml) in 46 patients (54%). In non-survivors (n=20), conventional cTnT was elevated (≥0.03ng/ml) in 2 patients (2%) and hs-cTnT was elevated (≥0.01ng/ml) in 17 patients (85%). In the stepwise multivariate analyses, a high plasma level of BNP (P=0.002), low left ventricular ejection fraction (<30%, P=0.012) and high hs-cTnT (≥0.01ng/ml, P=0.006) were independent significant prognostic predictors, but conventional cTnT (≥0.03ng/ml) was not. Conclusions: The findings of the present study indicated that a high serum concentration of hs-cTnT is a useful prognostic predictor that is independent of LVEF or BNP in CHF patients with non-ischemic DCM, suggesting that an increased hs-cTnT concentration sensitively reflects ongoing myocardial damage. (Circ J 2011; 75: 656-661)

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Background: Electrical and structural remodeling, characterized by prolonged action potential duration (APD), Kv4.2 downregulation and cellular infiltration were studied in rat experimental autoimmune myocarditis (EAM). Because the reactive oxygen species (ROS) has been speculated to play a role in the promotion of such remodeling, the effect of N-acetylcysteine (NAC) on the progression of ventricular remodeling was evaluated. Methods and Results: Six-week-old Lewis rats were immunized with porcine cardiac myosin. On Days 10-11 after the immunization, NAC (0, 1, 10, or 100mg) was injected intraperitoneally to EAM and control rats. On Day 14, the electrophysiological parameters were evaluated and the expression levels of the mRNA were examined by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR).The EAM rats exhibited a typical acute myocarditis with prolonged APD and reduced Kv4.2 expression as previously reported. The myocarditis and electrical changes were significantly suppressed by NAC-treatment in a dose-dependent manner (P<0.05). In rats with 100mg NAC, the myocarditis was almost totally negated although the mortality increased. In rats with 1mg NAC, the suppression of myocarditis was not obvious, but APD prolongation and Kv4.2 reduction was attenuated (P<0.05). Conclusions: The NAC treatment suppressed ventricular remodeling in the EAM rats. This may indicate the role of oxidative stress in causing remodeling and myocarditis itself in the acute phase of myocarditis. (Circ J 2011; 75: 662-671)

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Background: Idiopathic ventricular tachycardia (VT) has been reported to have a good prognosis, but there still might be the potential risk of sudden death. Methods and Results: The 46 consecutive children (mean age 11.7±3.4 years) with idiopathic VT were enrolled in this study. Monomorphic VT was detected in 39 patients and polymorphic VT in 7 patients. The VT originated from the right ventricle (RV) in 22 patients, and left ventricle (LV) in 17 patients. The VT was induced by exercise in 68% of the RVVT, 41% of the LVVT, and 100% of the polymorphic VT. The VT was induced by programmed ventricular stimulation in 41% of the RVVT, 35% of the LVVT, and none of the polymorphic VT. Adenosine tri-phosphate terminated the VT in 9 of 15 patients (60%). The mechanism of the VT was suspected to be triggered by activity in 36.4%, automaticity in 40.9%, and re-entry in 22.7% of the RVVT, whereas it was 52.9%, 5.9%, and 41.2% of the LVVT, respectively. Conclusions: The exercise inducibility was higher in polymorphic VT than the RVVT and LVVT, but no difference in the programmed stimulation. The sensitivity to adenosine tri-phosphate was not different between the RVVT and LVVT. In some patients with idiopathic VT, a non-verapamil sensitive re-entry was documented, which was more common in patients with ischemic heart disease or cardiomyopathy. (Circ J 2011; 75: 672-676)

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Background: There is evidence that phosphodiesterase type-5 is effective for the treatment of pulmonary arterial hypertension (PAH). Methods and Results: A phase III, multicenter, open-label clinical trial of sildenafil 20mg t.i.d. was conducted in 21 Japanese patients with PAH to examine its efficacy, safety, and pharmacokinetics. The present trial consisted of a screening period and 12-week treatment. Patients who were enrolled in the present trial increased their 6-min walking distance of administration increased at week 12 by 84.2m from baseline. Hemodynamic parameters (eg, mean pulmonary artery pressure and pulmonary vascular resistance), Borg dyspnea scores, and plasma brain natriuretic peptide concentrations also improved compared to baseline. Most patients improved or sustained WHO functional class. Seven subjects, who were examined for the pharmacokinetics of sildefanil, showed relatively large interindividual variations in the C_max, AUC_0-8, C_ss,av, and C_trough of the drug. Any serious adverse events, severe adverse events, and deaths were not observed. Most of events of undeniable causality were mild or moderate in severity. Sildefanil was well tolerated by the subjects. Conclusions: Sildenafil 20mg t.i.d. was effective and safe for Japanese patients with PAH. (Circ J 2011; 75: 677-682)

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Background: We analyzed in the present study the influence of intracoronary autologous freshly isolated bone marrow cells transplantation (BMCs-Tx) on cardiac function in patients with acute myocardial infarction (AMI). Methods and Results: The 32 patients with AMI were enrolled in this prospective nonrandomized study to either freshly isolated BMC-Tx or to a control group without cell therapy. Global left ventricular ejection fraction (LVEF) and the size of infarct area were determined by left ventriculography. We observed in patients with autologous freshly isolated BMCs-Tx at 6 months follow up a significant reduction of infarct size as compared to control group. Moreover, we found a significant increase of LVEF as well as infarct wall movement velocity at 6 months follow up in cell therapy group as compared to control group. In the control group there was no significant difference of LVEF, infarct size and infarct wall movement velocity between baseline and 6 months after AMI. Conclusions: These results demonstrate for the first time that intracoronary transplantation of autologous freshly isolated BMCs by use of a point of care system is safe, and may lead to improvement of cardiac function in patients with AMI. (Circ J 2011; 75: 683-691)

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Background: There is very little information about the relationship between hyperuricemia, acute kidney injury (AKI) and in-hospital mortality. Methods and Results: With a retrospective analysis of the medical records, 1,247 patients who had percutaneous coronary intervention (PCI) were investigated. AKI was defined as an increase in serum creatinine of ≥0.5mg/dl or ≥50% over baseline within 7 days of PCI. The association of AKI with clinical, biochemical and procedural variables were examined. In addition, the association of hyperuricemia with in-hospital mortality was also examined. Of the 1,247 patients in the study population, 51 (4.1%) experienced AKI after PCI, 15 of whom required hemodialysis. In-hospital mortality occurred in 1.6% (20 of 1,247) in 19.6% (10 of 51) of AKI individuals, and 0.8% (10 of 1,186) of the non-AKI participants (odd ratios, 28.927; 95% confidence intervals, 11.411-73.328; P<0.001). In our study, the most powerful predictors of these variables were acute myocardial infarction, baseline estimated glomerular filtration rate (eGFR) <60ml·min^-1·1.73m^-2, diabetics mellitus, anemia and hyperuricemia. Notably, the incidence of AKI after PCI markedly increased in diabetic or hyperuricemic patients with a baseline eGFR of <60ml·min^-1·1.73m^-2. Conclusions: It is clear that AKI develops due to multiple risk factors. Our results indicate that hyperuricemia is independently associated with an increased risk of in-hospital mortality and AKI in patients treated with PCI. (Circ J 2011; 75: 692-697)

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Background: The brachial-ankle pulse wave velocity (baPWV) and cardio-ankle vascular index (CAVI) are used to evaluate arterial distensibility. The purpose of this study was to elucidate the acute and chronic effects of smoking on arterial stiffness as measured by baPWV and CAVI. Methods and Results: Ten male smokers were studied to evaluate the acute effect of smoking on arterial stiffness. To elucidate the chronic effect of smoking on arterial stiffness, 160 male active smokers were analyzed. CAVI and baPWV were calculated by measuring the pulse volume record, blood pressure (BP), and vascular length from heart to ankle. CAVI and baPWV were measured using a VaSera VS-1000. In the acute study, baPWV and CAVI increased immediately after smoking 1 cigarette. In the chronic study, baPWV and CAVI significantly correlated with mean BP (MBP) and the Brinkman index. In multiple regression analysis, baPWV independently correlated with MBP, and CAVI independently correlated with the Brinkman index, but not with MBP. Receiver-operating characteristics (ROC) curves of baPWV and CAVI to predict Brinkman index ≥500 demonstrated that the area under the ROC curve of CAVI was higher than that of baPWV. Conclusions: Smoking causes a significant increase in arterial stiffness as measured by baPWV and CAVI. CAVI correlated with the Brinkman index, which suggests that CAVI is a useful index of the degree of arterial stiffness caused by smoking. (Circ J 2011; 75: 698-702)

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Background: Several microRNAs (miRNAs) have been reported to regulate cardiovascular biological and pathological processes through inhibiting the translation of certain RNA transcripts. However, little is known about the association between miRNAs and vascular smooth muscle cell (VSMC) proliferation. The aim was to investigate the role of miRNAs in VSMC growth and the potential mechanism. Methods and Results: Primary VSMCs were isolated from the medial layer of the thoracic aorta obtained from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). miRNA microarrays were used to analyze the difference in miRNA expression between VSMCs of SHR and WKY rats and were validated using TaqMan real-time PCR. Of the potentially related genes under the influence of let-7d identified through literature search, KRAS was verified by western blot and functionally analyzed using miRNA mimics transfection and analysis of transfectants by cell enumeration was made using CCK-8 and flow cytometric analysis of cell cycle progression. let-7d-transfected VSMCs from SHR, WKY and human coronary arteries expressed significantly lower amounts of KRAS protein, displayed reduced cell growth and led to a greater number of cells in the G1 phase than the G2/M phases of the cell cycle. Conclusions: let-7d was significantly downregulated in VSMCs as an important regulator of cell proliferation. RAS might be involved in the proliferation regulation by let-7d. (Circ J 2011; 75: 703-709)

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Background: This study tested the hypothesis that adaptive servo-ventilation (ASV) therapy improves the prognosis of heart failure (HF) patients, regardless of the severity of sleep-disordered breathing (SDB). Methods and Results: 88 consecutive patients were divided into 4 groups based on ASV therapy and SDB severity. The incidence of HF, brain natriuretic peptide (BNP) levels, and left ventricular ejection fraction (LVEF) were followed for 12 months. Fewer HF events, together with an increase in LVEF and a decrease in BNP, occurred in ASV-treated patients with both non-to-mild and moderate-to-severe SDB. Conclusions: ASV therapy improves the short-term prognosis in HF-patients, regardless SDB severity. (Circ J 2011; 75: 710-712)

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Nuclear cardiology has played an important role in both diagnosis and risk assessments of coronary artery disease since early 1970. Among the non-invasive diagnostic tests, the great advantage of nuclear imaging is that this technique can obtain physiological information, such as myocardial perfusion, which is difficult to obtain by other techniques. When patients have inducible myocardial ischemia and sufficient viable myocardium, coronary revascularization treatment should be performed. Both stress myocardial perfusion imaging (MPI) and viability imaging provide important information. Another important aspect of stress perfusion imaging is that normal stress perfusion is associated with low risk for future cardiac events. Therefore, stress MPI plays an important role in the selection of an invasive therapeutic regime and also in avoiding unnecessary invasive procedures. As is the case for other imaging techniques, there have been many technical and instrumental developments in recent years in nuclear cardiology imaging, including new single-photon-emission computed tomography tracers, new pharmacological stress agents, a new generation of γ camera, and positron emission tomography. This review will address the advantages of nuclear cardiology in the clinical setting and recent developments in nuclear cardiology. (Circ J 2011; 75: 713-723)

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The increasing variety of available cardiac imaging techniques have made the investigation of coronary artery disease more complex. On the one hand, nuclear cardiology or myocardial perfusion imaging (MPI) allows accurate and reliable quantitative measurement of myocardial blood flow. On the other hand, a newer technique, cardiac magnetic resonance imaging (CMR) is an attractive alternative for achieving similar purposes without exposing patients to radiation hazards. With a higher spatial resolution, CMR is more sensitive for detecting subendocardial ischemia; small myocardial infarction and/or fibrosis, which cannot be achieved in a nuclear study. Nuclear MPI has dominated clinical practice over the past 3 decades on the basis of an extensive amount of research. More upcoming research on CMR would warrant more evidence-based data of its value for disease diagnosis, prognosis and risk stratification and incorporating it into the clinical diagnostic and management algorithm. (Circ J 2011; 75: 724-731)

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