Search

Background: Previous studies have demonstrated that intensive lipid lowering using rosuvastatin results in regression of coronary plaques. However, few data exist regarding lipid profiles over time, drug tolerability, and the effects of prior use of lipid lowering agents in patients on rosuvastatin treatment. Therefore, we studied these matters in a subanalysis of the Coronary Atherosclerosis Study Measuring Effects of Rosuvastatin Using Intravascular Ultrasound in Japanese Subjects (COSMOS)., Methods: Rosuvastatin was titrated for 76 weeks to attain LDL-C < 80 mg/dL in 213 Japanese dyslipidemic patients with CAD. Clinic visits were scheduled for every 4 weeks during the 76-week study period. Changes over time in lipid parameters, changes in those according to prior lipid-lowering therapy, and changes in those according to baseline lipid levels were evaluated in this subanalysis., Results: Overall, 126 patients completed the study. The mean rosuvastatin dose at the last observation carried forward was 16.9 mg (range, 2.5-20 mg). Rosuvastatin significantly increased HDL-C, lowered LDL-C, and improved the LDL-C/HDL-C ratio (all, P < 0.0001). Increases in serum HDL-C levels were significantly greater in patients with HDL-C < 40 mg/dL than in those with HDL-C ≥ 40 mg/dL at baseline (P = 0.0005). The estimated glomerular filtration rate increased significantly by 2.84 ± 9.01 mL/min/1.73 m(2) (P < 0.0001). Of 166 adverse events in 74 patients, 113 events in 54 patients were laboratory values beyond the normal range., Conclusion: Rosuvastatin significantly improved lipid profiles, with an acceptable safety profile, contributing to plaque regression in Japanese patients with CAD., (© 2013 John Wiley & Sons Ltd.)

Background: Hyperglycemia, a risk factor for development of cardiovascular disease, causes endothelial dysfunction. Alpha-glucosidase inhibitors (α-GIs) improve postprandial hyperglycemia (PPHG) and may have favorable effects on associated cardiovascular disease. Effects of α-GIs in patients with acute coronary syndrome (ACS) and PPHG remain unclear; thus, we assessed the effect of α-GI miglitol on endothelial function in such patients by digital reactive hyperemia peripheral arterial tonometry (RH-PAT)., Methods: Fifty-four patients with ACS who underwent primary percutaneous coronary intervention were enrolled in the study: 36 with new-onset PPHG and 18 with normal glucose tolerance. Eighteen PPHG patients were given 50 mg of miglitol with each meal for 1 week. Endothelial function was assessed on the basis of the RH-PAT index (RHI) before and after the 1-week miglitol treatment. The other 18 PPHG patients and the 18 NGT patients were not given any anti-diabetic agent for 1 week, and endothelial function was assessed., Results: Postprandial RHI decreased significantly in patients with PPHG. Miglitol improved PPHG significantly; postprandial RHI also improved (p = 0.007). Significant inverse correlation was found between the postprandial change in RHI and postprandial fasting-to-60-minutes surge in glucose (r = -0.382, p = 0.009). Moreover, the improvement in endothelial function correlated with the reduced postprandial glucose surge achieved with miglitol (r = -0.462, p = 0.001)., Conclusions: Postprandial changes in glucose are related to endothelial dysfunction in ACS. Miglitol-based improvement in PPHG appears to improve endothelial function. The effect of miglitol on glucose-dependent endothelial function might improve outcomes of ACS.

Background: A sigmoid ventricular septum (SVS) may be related to normal aging, but some people with an SVS develop a left ventricular outflow tract (LVOT) obstruction (defined as a gradient of >30 mmHg). Therefore, we investigated the association of LVOT obstructions with an SVS by dobutamine stress echocardiography (DSE) and assessed the possible mechanism of the latent LVOT obstruction., Methods and Results: DSE was performed in 64 subjects with SVS (mean age: 73.3±7.7 years; 36 women) without an LVOT obstruction. In 40 of the 64 subjects, an LVOT obstruction occurred during the DSE (defined as latent obstruction). At rest, the subjects with a latent obstruction had a shorter end-systolic mitral leaflet tethering distance ("α" distance, i.e. the distance between the tip of the posterior papillary muscle and the contralateral anterior mitral annulus) than those without one (29.9±4.2 mm versus 35.2±4.6 mm), as well as a smaller end-systolic LVOT diameter (13.4±2.7 mm versus 16.1±3.4 mm) and larger ejection fraction (72.0±5.0% versus 67.8±5.9%) (all p<0.05). They also had a higher LV outflow velocity at rest (1.23±0.24 m/s versus 1.03±0.24 m/s) and during the Valsalva maneuver (1.31±0.27 m/s versus 1.03±0.27 m/s) (both p<0.05). After adjusting for these parameters, the resting end-systolic "α" distance and LV outflow velocity at rest remained independent predictors of a latent obstruction., Conclusion: A short leaflet tethering distance ("α") was the major determinant of a latent obstruction, suggesting that a mitral leaflet displacement/redundancy caused by a short "α" distance contributes to the LVOT obstruction., (Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Diabetes mellitus (DM) is a major risk factor for cardiovascular events. The study purpose was to compare DM and non-DM (nDM) patients in terms of statin-induced change of plaque characteristics using intravascular ultrasound (IVUS) and coronary angioscopy., Methods: Patients with coronary artery disease and hypercholesterolemia who were enrolled to the TWINS were selected and classified into two groups: DM group and nDM group. Eleven DM patients and 28 nDM patients were studied., Results: Low-density lipoprotein cholesterol levels decreased significantly to a similar extent at weeks 28 and 80 from baseline in DM and nDM (p<0.001). The mean angioscopic color grades of yellow plaques in DM and nDM were similar at baseline and significantly decreased at week 80 from baseline in both groups, however, the mean change of angioscopic color grade from baseline in DM were not significantly decreased and the mean angioscopic color was significantly higher than that in nDM (1.34 vs. 1.00, p<0.05) at week 28. IVUS showed plaque volume reduction in both groups (p<0.01) except at week 80 in DM group, which was not statistically significant different compared to the baseline., Conclusion: In DM patients, plaque volume regression by atorvastatin was shown to be attenuated, and its color improvement was significantly delayed. However, the yellowness became comparable between DM and nDM groups at week 80. These results indicate that patients with DM should be treated by intensive lipid-lowering therapy with atorvastatin for at least 80 weeks to stabilize vulnerable plaque., (Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: The Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome (JAPAN-ACS) trial demonstrated that early aggressive statin therapy in patients with ACS significantly reduces plaque volume (PV). Advanced glycation end products (AGEs) and the receptors of AGEs (RAGE) may lead to angiopathy in diabetes mellitus (DM) and may affect on the development of coronary PV. The present sub-study of JAPAN-ACS investigates the association between AGEs and RAGE, and PV., Methods: Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) was undertaken, followed by the initiation of statin treatment (either 4 mg/day of pitavastatin or 20 mg/day of atorvastatin), in patients with ACS. In the 208 JAPAN-ACS subjects, PV using IVUS in non-culprit segment > 5 mm proximal or distal to the culprit lesion and, serum levels of AGEs and soluble RAGE (sRAGE) were measured at baseline and 8-12 months after PCI., Results: At baseline, no differences in the levels of either AGEs or sRAGE were found between patients with DM and those without DM. The levels of AGEs decreased significantly with statin therapy from 8.6 ± 2.2 to 8.0 ± 2.1 U/ml (p < 0.001), whereas the levels of sRAGE did not change. There were no significant correlations between changes in PV and the changes in levels of AGEs as well as sRAGE. However, high baseline AGEs levels were significantly associated with plaque progression (odds ratio, 1.21; 95% confidence interval, 1.01 - 1.48; p = 0.044) even after adjusting for DM in multivariate logistic regression models., Conclusions: High baseline AGEs levels were associated with plaque progression in the JAPAN-ACS trial. This relationship was independent of DM. These findings suggest AGEs may be related to long-term glucose control and other oxidative stresses in ACS., Trial Registration: NCT00242944.

Background: Matrix metalloproteinases (MMPs) have been implicated in development of atherosclerosis. MMPs are activated in patients with acute coronary syndrome (ACS). However, little data exist regarding the correlation between circulating levels of MMPs and plaque volume (PV) in patients with ACS. We therefore evaluated the impact of MMPs on coronary PV as a post hoc analysis from the JAPAN-ACS study., Methods: The multicenter JAPAN-ACS trial revealed that aggressive statin therapy for patients with ACS significantly reduces coronary PV determined by intravascular ultrasound (IVUS). We studied 248 ACS patients who had serial IVUS examinations over 8-12 months in the trial. For each patient, MMP-1, 2, and 3 were measured both at baseline and at study end to evaluate the correlation between the percent change of PV and MMP levels., Results: MMP-3 levels were significantly decreased during the follow-up period (100 ng/mL to 73 ng/mL, p < 0.001), in contrast, MMP-1, -2 levels were significantly increased. MMP-3 levels at follow-up correlated with coronary plaque regression (p for trend = 0.016). A multivariable linear regression model showed both MMP-2 and MMP-3 levels at follow-up were independent variables for change of coronary PV (p = 0.038 and p = 0.016, respectively)., Conclusion: Circulating MMPs levels are associated with changes in coronary plaque volume determined by serial IVUS in patients with ACS., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

There are different ways of closing extraction spaces with lingual orthodontics. One is to use loop mechanics and the other is to use sliding mechanics. This case report describes the treatment of closing spaces using sliding mechanics with and without the use of microscrews. Understanding and applying basic biomechanical principles is necessary for lingual orthodontics and the use of miniscrews. The purpose of this article is to demonstrate the effect of orthodontic miniscrews in controlling anchorage and the basic biomechanical considerations in understanding the influence of the anterior teeth.

Objectives: To examine serial change in the residual plaque behind the sirolimus-eluting stent (SES) using coronary angioscopy in patients with SES implantation and to identify its baseline determinants., Background: Previous coronary angioscopic studies have demonstrated that SES enhances the yellow grade of residual plaque during follow-up period., Methods: A total of 42 patients with stable angina pectoris or silent ischemic heart disease, who had a successful SES implantation were examined by coronary angioscopy both at the baseline (SES implantation) and the follow-up period (9-14 month follow-up). The patients were divided into three groups as: worsened group (WS: yellow color grade of coronary plaque at the follow-up period was worsened compared to the baseline period, n=15), no change group (NP: no change compared to the baseline, n=16), and improved group (IP: improved compared to the baseline, n=11). Then, the determinants of the nominal change of yellow color grade were examined by multiple regression analysis., Results: The low-density lipoprotein cholesterol (LDL-C) level in IP group at the follow-up was significantly decreased compared to baseline (from 120.0±29.8mg/dl to 74.3±16.7mg/dl, p=0.0005), and was the lowest among three groups (WS: 103.5±16.4mg/dl, NC: 105.7±18.7mg/dl, and IP: 74.3±16.7mg/dl). Multiple regression analysis revealed that family history, statin administration, baseline serum creatinine, baseline 'in-stent' thrombus, and follow-up LDL-C were significant determinants to the nominal change of yellow color grade after the SES implantation (p<0.0001)., Conclusions: Serial change in tissue characteristics within residual plaque under SES is determined by several factors, especially LDL-C level as well as statin administration. Adequate management of LDL-C by statins might be crucial for stabilizing residual plaque after SES implantation., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)

Background: Although increased epicardial adipose tissue (EAT) volume is known to be associated with increased prevalence of atrial fibrillation (AF), the exact mechanisms are unclear. Therefore, we investigated whether EAT locations were associated with high dominant frequency (DF) sites or complicated fractionated atrial electrogram sites during AF., Methods and Results: Three-dimensional reconstruction computed tomography images depicting EAT volumes (obtained by 320-detector-row multislice computed tomography) were merged with NavX-based DF and complicated fractionated atrial electrogram maps obtained during AF for 16 patients with paroxysmal AF and for 18 patients with persistent AF. Agreement between locations of the EAT, especially EAT surrounding the left atrium, and of high DF or complicated fractionated atrial electrogram sites was quantified. In addition, serum biomarker levels were determined. EAT surrounding the left atrium volumes was significantly greater in patients with persistent AF than in patients with paroxysmal AF (52.9 cm(3) [95% CI, 44.2-61.5] versus 34.8 cm(3) [95% CI, 26.6-43.0]; P=0.007). Serum high-sensitivity C-reactive protein and interleukin-6 levels were significantly higher in persistent AF patients than in paroxysmal AF patients (median high-sensitivity C-reactive protein, 969 ng/mL [interquartile range, 307-1678] versus 320 ng/mL [interquartile range, 120-660]; P=0.008; median interleukin-6, 2.4 pg/mL [interquartile range, 1.7-3.2] versus 1.3 [interquartile range, 0.8-2.4] pg/mL; P=0.017). EAT locations were in excellent agreement with high DF sites (κ=0.77 [95% CI, 0.71-0.82]) but in poor agreement with complicated fractionated atrial electrogram sites (κ=0.22 [95% CI, 0.13-0.31])., Conclusions: Increased EAT volume and elevation of inflammatory biomarkers are noted in persistent AF rather than paroxysmal AF patients. High DF sites are located adjacent to EAT sites. Thus, EAT may be involved in the maintenance of AF.

Background: The incidence of cardiac events is higher in patients with diabetes than in people without diabetes. The Coronary Atherosclerosis Study Measuring Effects of Rosuvastatin Using Intravascular Ultrasound in Japanese Subjects (COSMOS) demonstrated significant plaque regression in Japanese patients with chronic coronary disease after 76 weeks of rosuvastatin (2.5 mg once daily, up-titrated to a maximum of 20 mg/day to achieve LDL cholesterol <80 mg/dl)., Methods: In this subanalysis of COSMOS, we examined the association between HbA1c and plaque regression in 40 patients with HbA1c ≥6.5% (high group) and 86 patients with HbA1c <6.5% (low group)., Results: In multivariate analyses, HbA1c and plaque volume at baseline were major determinants of plaque regression. LDL cholesterol decreased by 37% and 39% in the high and low groups, respectively, while HDL cholesterol increased by 16% and 22%, respectively. The reduction in plaque volume was significantly (p = 0.04) greater in the low group (from 71.0 ± 39.9 to 64.7 ± 34.7 mm(3)) than in the high group (from 74.3 ± 34.2 to 71.4 ± 32.3 mm(3)). Vessel volume increased in the high group but not in the low group (change from baseline: +4.2% vs -0.8%, p = 0.02). Change in plaque volume was significantly correlated with baseline HbA1c., Conclusions: Despite similar improvements in lipid levels, plaque regression was less pronounced in patients with high HbA1c levels compared with those with low levels. Tight glucose control during statin therapy may enhance plaque regression in patients with stable coronary disease., Trial Registration: ClinicalTrials.gov, Identifier NCT00329160.

Background: The JAPAN-ACS (Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome) trial showed that intensive statin therapy could induce significant coronary plaque regression in acute coronary syndrome (ACS). We evaluated the impact of metabolic syndrome (MetS) and its components on coronary plaque regression in the JAPAN-ACS patients., Methods and Results: Serial intravascular ultrasound measurements over 8-12 months were performed in 242 ACS patients receiving pitavastatin or atorvastatin. Patients were divided into groups according to the presence of MetS or the number of MetS components. Although the percent change in plaque volume (%PV) was not significantly different between the MetS (n=119) and non-MetS (n=123) groups (P=0.50), it was significantly associated with an increasing number of MetS components (component 0: -24.0%, n=7; components 1: -20.8%, n=31; components 2: -16.1%, n=69; components 3: -18.7%, n=83; components 4: -13.5%, n=52; P=0.037 for trend). The percent change in body mass index (%BMI) significantly correlated with %PV (r=0.15, P=0.021), especially in the MetS components 4 group (r=0.35, P=0.017). In addition, %BMI was an independent predictor of plaque regression after adjustment for the changes of low- and high-density lipoprotein cholesterol, triglycerides and HbA(1c)., Conclusions: The clustering of MetS components, but not the presence of MetS itself, could attenuate coronary plaque regression during intensive statin therapy in ACS patients. Therefore, to achieve a greater degree of plaque regression, it is necessary to treat to each MetS component and use lifestyle modification.

Background: The JAPAN-ACS study demonstrated that statins significantly reduced coronary plaque volume in patients with acute coronary syndrome (ACS). The clinical implications of plaque regression for clinical outcomes in ACS patients has not been established. The Extended JAPAN-ACS study was conducted to evaluate the relationship between coronary plaque regression and long-term clinical outcome, and to explore the factors associated with cardiovascular events., Methods and Results: Patients with intravascular ultrasound (IVUS) data at both enrollment and follow-up in the JAPAN-ACS study were enrolled and observed for at least 3 years. Patients were divided into lesser and greater coronary plaque regression groups. The primary endpoint was defined as a composite of the following events: cardiovascular death, nonfatal myocardial infarction, nonfatal cerebral infarction, and unstable angina. The median value of the percent change in plaque volume, 18.0%, was used as a cutoff point. There were 4 primary events (3.4%) in the lesser regression group, and 2 events (1.7%) in the greater regression group (P=0.4). Cumulative secondary cardiovascular events did not differ between the 2 groups. Multivariate analysis identified the high-density lipoprotein cholesterol (HDL-C) at baseline and the % change of the external elastic membrane volume as independent risk factors of cardiovascular events., Conclusions: Coronary plaque regression induced by an intensive statin regimen did not predict future cardiovascular events in ACS patients. Rather, the baseline HDL-C level and reverse vessel remodeling might serve as predictors for cardiovascular events.

Aim: To clarify whether the effects of statin treatment on plaque regression vary according to the presence or absence of polyvascular disease (PVD) in patients with acute coronary syndrome (ACS)., Methods: 307 patients with ACS who underwent percutaneous coronary intervention for the culprit lesion at 33 centers were treated with atorvastatin or pitavastatin. Noncoronary atherosclerosis was defined as coexistent, clinically recognized arterial disease other than coronary artery disease (CAD) (cerebral, aortic, or lower extremity). Intravascular ultrasound (IVUS) was performed to assess non-culprit coronary atherosclerosis at baseline and at 8-12 months follow-up. Serial IVUS examinations were obtained in 252 patients. Atheroma volume and percent change in atheroma volume of the target plaque was assessed., Results: Patients of the CAD+PVD (n = 19) were older (68 vs. 62 years, p = 0.02), had lower low-density lipoprotein cholesterol (LDL-C) levels at baseline (116 vs. 134 mg/dL, p=0.03) than those of the CAD-only group (n = 233), whereas LDL-C levels at follow-up were similar (81 vs. 83 mg/dL). Although the baseline plaque volume was similar in the two groups (59 vs. 57 mm(3)), patients of the CAD+PVD group showed milder regression of atherosclerosis than those of the CAD-only group (-8.9% vs. -18.2%, p = 0.005). This difference remained significant even after adjustment for coronary risk factors including age and serum LDL-C (p = 0.047)., Conclusions: Statin treatment results in milder regression of coronary atherosclerosis in CAD patients with polyvascular disease compared to those with CAD only., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Coronary stents have been used for the treatment of patients with coronary artery disease (CAD), and significantly improved procedural safety and are associated with a lower rate of restenosis compared with balloon angioplasty alone. Drug-eluting stents (DES) have been dominant for the treatment of CAD with efficacy in significantly reducing both restenosis and target lesion revascularization. However, late and very late stent thrombosis have become a major concern in DES-implanted arteries compared with those treated with bare-metal stents (BMS). This review focuses on the feature of DES thrombosis and pathological examination and dual antiplatelet therapy for prevention of stent thrombosis. Currently, the incidence of stent thrombosis associated with first-generation and second-generation DES remains unclear in data from real-world cohort registry studies. Further studies of larger multicenter trials would give us insight into the specific mechanisms of stent thrombosis among different generations of DES., (Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objective: This study was conducted to examine the virtual unipolar electrogram configuration of right/left outflow tract (OT) premature ventricular contraction (PVC)/ventricular tachycardia (VT) origins obtained from a non-contact mapping system (NCMS)., Methods: The subjects consisted of 30 patients with OT-PVCs/VT who underwent NCMS-guided ablation. We evaluated the virtual unipolar electrograms of the origin on 3D right ventricular (RV)-OT isochronal maps., Results: Successful ablation was achieved from the RV in 20 patients (RVOT group), and it failed in 10 (non-RVOT group: including left-sided/pulmonary artery/deep RVOT foci). On the virtual unipolar electrograms, the earliest activation (EA) preceded the QRS onset by 11.2 ± 2.6 ms in the RVOT group and by 7.4 ± 10.5 ms in the non-RVOT group (P = 0.138). The negative slope of the electrogram at the EA site (EA slope(5)), quantified by the virtual unipolar voltage amplitude 5 ms after the EA onset, was significantly steeper in the RVOT group than in the non-RVOT group (0.66 ± 0.52 mV vs. 0.14 ± 0.17 mV, P = 0.005). Cutoff values for the EA-to-QRS onset time and EA slope(5) of ≥ 8 ms and >0.3 mV, respectively, completely differentiated the RVOT group from the non-RVOT group. A lesser EA slope(5) was associated with a greater radiofrequency energy delivery required to terminate RVOT-PVCs/VT., Conclusions: These demonstrate the importance of the virtual unipolar electrograms from OT-PVC/VT origins obtained with the NCMS. The virtual EA predicts both successful and potentially difficult ablation sites from the RV side.

Background: A previous study reported that amlodipine retarded coronary plaque progression in patients with coronary artery disease. The goal of this multicenter study was to determine which calcium-channel blockers (CCBs) other than amlodipine attenuated the progression of plaque volume (PV) accessed by intravascular ultrasound (IVUS)., Methods and Results: ALPS-J was a prospective, randomized open-label study conducted at 5 centers. Patients who had hypertension and were scheduled for coronary intervention were enrolled. Subjects were randomly assigned to receive 16 mg/day of azelnidipine or 5mg/day of amlodipine administered for 48 weeks. The primary endpoint was the percent change in coronary PV measured by IVUS. Between 2007 and 2009, 199 patients were enrolled; 115 had evaluable IVUS images at both baseline and after 48 weeks of treatment. Blood pressure significantly reduced to 128/68 mmHg at follow-up. The lipid profiles in the 2 groups were comparable (low-density lipoprotein cholesterol: 97 mg/dl). The %change in PV showed a significant regression of 4.67 and 4.85% in the azelnidipine and amlodipine groups, respectively. The upper limit of the 95% confidence interval of the mean difference in %change PV between the 2 groups (0.18%, 95% confidence interval 4.62 to 4.98%) did not exceed the pre-defined non-inferiority margin of 6.525%., Conclusions: ALPS-J demonstrated that azelnidipine was not inferior to amlodipine for primary efficacy. In addition to standard medical therapy, dihydropyridine CCBs will retard PV progression in hypertensive patients.

This article reviews the treatment of patients with multivessel coronary artery disease (CAD). Percutaneous coronary intervention (PCI) has been challenging coronary artery bypass grafting (CABG) as the gold standard of care for patients with multivessel disease; however, the application of PCI to these patients has been mainly limited by restenosis. Up to the beginning of the 2000s, many large-scale, randomized trials addressed this issue by comparing CABG to PCI with balloon angioplasty or bare metal stents in not only Western countries but also in Asian countries. These studies demonstrated similar rates of all-cause death and myocardial infarction in both groups, although the need for revascularization remained significantly lower in the CABG group. PCI with drug-eluting stents (DES) is safe and may represent a viable alternative to CABG for selected patients with diabetes and multivessel CAD. Moreover, DES implantation under intravascular ultrasound guidance and with fractional flow reserve might have the potential to influence treatment strategy and reduce both DES thrombosis and repeat revascularization. The evolution of DES and advanced vascular imaging would mean that PCI continues to challenge CABG as treatment of choice for patients who need revascularization for a better prognosis.

Aim: We have shown that aggressive lipid lowering by pitavastatin and atorvastatin results in marked regression of atherosclerotic coronary lesions after acute coronary syndrome (ACS). The purpose of this study was to address the association of lipid levels after statin therapy with regression of atherosclerotic coronary lesions and major cardiovascular events in patients after ACS., Methods: JAPAN-ACS is a prospective, randomized open-label study performed at 33 centers in Japan. Patients with ACS undergoing intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) were randomly assigned to receive either 4 mg/day pitavastatin or 20 mg/day atorvastatin within 72 hours after PCI. IVUS image was obtained in 251 patients, including 73 diabetic patients. Lipid profiles at the end of the study were divided into quartiles and the association with the percent change in non-culprit coronary plaque volume (PV) was assessed in total and diabetic patients. We also studied whether baseline and follow-up levels of HDL-cholesterol are associated with restenosis after PCI., Results: Decreasing LDL-cholesterol, non-HDL-cholesterol, LDL-C/HDL-C ratio, apolipoprotein B quartiles were associated with a progressively smaller plaque burden in total and diabetic patients. In diabetic patients, further reduction of these parameters was associated with a significantly greater reduction in PV. We also found that patients with lower HDL-cholesterol had a significantly higher incidence of target lesion revascularization., Conclusions: Early intensive statin therapy in patients after ACS results in remarkable regression of coronary PV. Diabetic patients can have a benefit with more intensive therapy to achieve a lower target level in Japanese.

Objective: The Japan assessment of pitavastatin and atorvastatin in acute coronary syndrome (JAPAN-ACS) study demonstrated that aggressive lipid-lowering therapy with a statin resulted in a significant regression of coronary atherosclerotic plaques in patients with ACS. Adiponectin is an adipocyte-derived protein with anti-atherogenic properties. Here, we investigated the association between adiponectin levels and the change in the plaque volume in ACS patients., Methods: Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) was undertaken, followed by the initiation of statin treatment, in 238 patients with ACS. Follow-up IVUS was performed between 8 and 12 months after the PCI. The percent change in the plaque volume (%PV) in a non-culprit coronary artery segment was evaluated. The serum adiponectin and lipid parameters were measured both at baseline and at the follow-up., Results: At baseline, adiponectin was correlated positively with HDL-cholesterol and negatively correlated with triglyceride, but no correlation was observed with the PV. Adiponectin levels increased significantly from 7.8+/-4.6 microg/mL at baseline to 10.3+/-6.9 microg/mL at the 8-12 months follow-up. The increase in adiponectin was also associated with an increase of HDL-cholesterol and decrease of triglyceride, however, no significant correlation was observed with the %PV. A significantly higher incidence of major adverse cardiac events (MACE) was observed in patients with hypo-adiponectinemia at baseline. A multiple logistic regression analysis identified adiponectin as a significant independent predictor of MACE., Conclusion: Adiponectin levels measured after PCI could serve as a marker of MACE in patients with ACS., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: The Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome (JAPAN-ACS) trial has found that early aggressive statin therapy in patients with acute coronary syndrome (ACS) significantly reduces the plaque volume (PV) of non-culprit coronary lesions. The purpose of the present study was to evaluate clinical factors that have an impact on plaque regression using statin therapy., Methods and Results: Serial intravascular ultrasound observations over 8-12 months were performed in 252 ACS patients receiving pitavastatin or atorvastatin. Linear regression analysis identified the presence of diabetes mellitus (DM) and PV at baseline as inhibiting factors, and serum remnant-like particle-cholesterol level at baseline as a significant factor significantly affecting the degree of plaque regression. Significant correlation between % change of PV and low-density lipoprotein cholesterol (LDL-C) level was found in patients with DM (n=73, P<0.05, r=0.4), whereas there was no significant correlation between the 2 parameters in patients without DM (n=178)., Conclusions: The regression of coronary plaque induced by statin therapy after ACS was weaker in diabetic patients than their counterparts. Moreover, vigorous reduction of the LDL-C levels might induce a greater degree of plaque regression in ACS patients with DM.

Plaque rupture leads to acute coronary syndrome (ACS including STEMI, NSTEMI, unstable angina). Medical and revascularization therapy was established for the patients with ACS. Coronary stent has been developed from bare metal stent to drug eluting stent. Moreover revascularization for ACS has been changing from stenting alone to facilitated stenting (use of thrombolytic agent before stent implantation) in Japan. Distal protection device has been attracted attention to new trend for ACS patients. Coronary stent is going to new generation and stenting for ACS is also changing in near future.

Background: It has been suggested that intensive lipid-lowering therapy using statins significantly decreases atheromatous plaque volume. The effect of rosuvastatin on plaque volume in patients with stable coronary artery disease (CAD), including those receiving prior lipid-lowering therapy, was examined in the present study., Methods and Results: A 76-week open-label trial was performed at 37 centers in Japan. Eligible patients began treatment with rosuvastatin 2.5 mg/day, which could be increased at 4-week intervals to

Objectives: The purpose of the present study was to assess the relationship between shear stress distribution and coronary plaque rupture by means of a new color-mapping program of shear stress with 3-dimensional intravascular ultrasound (IVUS)., Background: Various in-vitro studies have demonstrated that shear stress of the vascular lumen is one of the important determinants of coronary plaque vulnerability. However, the in-vivo relationship between shear stress and plaque rupture is still unclear., Methods: In the present study, 3-dimensional IVUS was used to obtain spatial information on luminal geometry from 20 patients with acute coronary syndrome having a distinct ulcerative lesion. These 3-dimensional contours for each lumen were first reconstructed into mesh polygons, and then analyzed by means of a program for calculating the fluid dynamics. The flow was considered to be a constant laminar one. Then, colorized mappings of the distribution of the streamline, blood pressure, and shear stress were performed. The original luminal contour for each ruptured lesion was obtained by smoothing and extrapolation., Results: All patients had a coronary plaque rupture in the proximal or top portion of the plaque hill. In the color mapping, localized elevation of blood pressure and shear stress could be observed on each plaque surface. The shear stress concentration was frequently correlated with the plaque rupture site (kappa = 0.79)., Conclusions: Although the absolute value of shear stress is not sufficient to directly provoke mechanical destruction of the fibrous cap, localized high shear stress might be a trigger of fibrous cap rupture.

A 73-year-old female underwent percutaneous coronary intervention (PCI) because of stable angina. An elective PCI for the RCA lesion was first performed with deploying sirolimus eluting stents (SES). Three weeks later, PCI was also provided in the residual LAD lesion. Eight months later, she presented with new angina. CAG revealed an in-stent restenosis in the mid LAD and a large eccentric saccular coronary aneurysm (17 mm x 9 mm) at the proximal RCA. Intravascular ultrasound (IVUS) showed absence of stent struts around the orifice of aneurysm, which suggested a fracture of SES stent. The entry of coronary aneurysm was finally sealed with a polytetrafluoroethylene-covered stent. This report documented a rare case of late giant coronary artery aneurysm associated with a fracture of SES.

The indirect bonding technique is pivotal for success in lingual orthodontics. There are different laboratory techniques available for indirect positioning and bonding of lingual brackets. The HIRO system is one of the most used and easy to perform. In this article the HIRO laboratory and bonding technique and the different innovations and improvements made to the previously described technique are presented.

Background: There have been few multicenter studies using intravascular ultrasound (IVUS) to assess the process of atherosclerosis in a Japanese population with hypercholesterolemia that is being treated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors for control of low-density lipoprotein-cholesterol., Methods and Results: An open-label multicenter study is planned to evaluate with IVUS whether treatment with rosuvastatin for 76 weeks results in regression of coronary artery atheroma volume in patients who have coronary heart disease (CHD) and hypercholesterolemia. Sample size is 200 subjects with CHD who are to undergo percutaneous coronary intervention. The planned duration is between October 2005 and October 2008., Conclusions: The COSMOS study will be the first multicenter cardiovascular study in a Japanese population and may provide new evidence on the effects of rosuvastatin on the progression of coronary atherosclerotic lesions.

Background: Many trials have shown that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors reduce the incidence of cardiovascular events and mortality. One method of decreasing the incidence of cardiovascular events could be to reduce the progression of coronary atherosclerosis, and a recent study found that atorvastatin can cause coronary plaque to regress. To generalize this finding, using conventional HMG-CoA reductase inhibitors at many Japanese centers, randomized trials of pitavastatin and atorvastatin will be conducted with patients with acute coronary syndrome (ACS)., Methods and Results: Patients with ACS who have undergone successful percutaneous coronary intervention under intravascular ultrasound guidance will be studied. They will be randomly allocated to pitavastatin or atorvastatin groups and followed up for 8-12 months. The primary endpoint will be the percent change in coronary plaque volume, and secondary endpoints will include absolute changes in coronary plaque volume, serum lipid levels and inflammatory markers. The safety profile will also be evaluated., Conclusions: This study will examine the ability of HMG-CoA reductase inhibitors to regress coronary plaque in Japanese patients with ACS and the findings should help to improve the prognosis of such patients and clarify the involved mechanisms.

Diabetes mellitus (DM) is an independent and distinct risk factor of ischemic heart disease. Therefore, early identification and management of coronary atherosclerosis for patients with DM is being desired. For the purpose of visualizing coronary atherosclerosis, various imaging modalities have been proposed especially to identify an unstable plaque that has a thin fibrous cap and a large lipid core. These modalities include intravascular ultrasound, coronary angioscopy, intracoronary thermography, optical coherence tomography, multi-slice CT, MRI, and so on. The development of these modalities are now pushing all cardiologists to get interested in a new field called as "plaque imaging".

Objectives: This study theoretically examined the longitudinal structural determinants of plaque vulnerability using a color-coded stress mapping technique for several hypothetical vessel models as well as three-dimensional intravascular ultrasound (IVUS) images with use of a finite element analysis., Background: It has been shown that an excessive concentration of stress is related to atherosclerotic plaque rupture. However, the local determinants of in-plaque longitudinal stress distribution along the coronary arterial wall remain unclear., Methods: Using a finite element analysis, we performed a color mapping of equivalent stress distribution within plaques for three-dimensional vessel models as well as longitudinal IVUS plaque images (n = 15). Then, the effects of plaque size, shape, expansive remodeling, calcification, and lipid core on the equivalent stress distribution were examined., Results: The color mapping of vessel models revealed a concentration of equivalent stress at the top of the hills and the shoulders of homogeneous fibrous plaques. Expansive remodeling and the lipid core augmented the surface equivalent stress, whereas luminal stenosis and superficial calcification attenuated the equivalent stress. The location of excessive stress concentration was modified by the distribution of the lipid core and calcification. The thickness of the fibrous cap was inversely related to the equivalent stress within the fibrous cap. However, the color mapping of IVUS plaque images showed that the equivalent stress value at the fibrous cap varied with changes in plaque shape and superficial calcification, even when the thickness of the fibrous cap remained constant., Conclusions: A distribution analysis of longitudinal stress revealed specific effects of plaque shape, size, and remodeling, as well as effects of the interior distribution of tissue components, on the concentration of stress at the plaque surface. Moreover, fibrous caps of the same thickness did not consistently represent the same vulnerability to rupture.

Objectives: This study examined the feasibility of using a wavelet analysis of radiofrequency (RF) intravascular ultrasound (IVUS) signals in detecting lipid-laden plaque., Background: Wavelet analysis is a new mathematical model for assessing local changes in a geometrical profile of time-series signals., Methods: Radiofrequency IVUS signals of 85 arbitrarily selected vectors were acquired from 27 formalin-fixed noncalcified atherosclerotic plaques from human necropsy with a digitizer at 500 MHz with 8-bit resolution by use of a 40-MHz IVUS catheter. Wavelet analysis of these RF signals was performed using a Daubechies-2 wavelet to obtain a color-coded map of the correlation coefficient with the wavelet reconstructed over the x-y plane of the wavelet scale and the distance from the IVUS catheter. The plaque segment was then examined histologically after being stained with Masson's trichrome stain. This technique also was applied in vivo in 29 human coronary plaque segments. These segments were excised subsequently by directional coronary atherectomy and processed for histologic analysis., Results: In the in vitro study, histologic examination revealed lipid-laden segments in 29 vectors. When performing a wavelet analysis with the Daubechies-2 wavelet, the color-coded mapping revealed a different pattern in lipid-laden plaques compared with other types of plaque. Using this wavelet analysis, lipid-laden plaque could be detected with a sensitivity of 83% (24 of 29) and a specificity of 82% (46 of 56). In the in vivo study, fatty plaque could be detected with a sensitivity of 81% (13 of 16) and a specificity of 85% (11 of 13) with this method., Conclusions: Wavelet analysis of RF IVUS signals enabled in vitro as well as in vivo detection of lipid-laden plaque. This method may be useful in assessing plaque vulnerability in patients with coronary artery disease.

To establish the relationship between the cross-sectional geometry of the post-deployment stent and the degree of in-stent neointimal hyperplasia (INH), intravascular ultrasound (IVUS) was used to examine cross-sections of the coronary arteries from 23 patients with coronary stents 6 months after implantation. Stent cross-sectional area (Sa) and stent perimeter (Sp) from 200 stent cross-sections, and the stent radius (Sr) and thickness of INH (Id) of 2,880 radial axes, were measured, and the mean degree of roundness (Rd) of stent cross-section was calculated for each stent as Rd=4piSa/Sp2. The degree of deformity (Df) of the stent cross-section was also calculated by comparing it with a hypothetical circle (the area of this hypothetical circle was equal to the Sa): Df=Sr/R, where R is the radius of the hypothetical circle. The area of INH was significantly larger in the Rd<0.87 group (n=84) than in the Rd> or =0.87 group (n=116) (3.83+/-1.26 vs 3.16+/-1.32 mm2, p<0.0005). There were significant differences in the thickness of INH among the 3 groups classified by the value of Df (Df<0.95: n=425, 0.21+/-0.12mm; 0.95< or =Df<1.05: n=2008, 0.29+/-0.15mm; Df> or =1.05: n=447, 0.34+/-0.15mm, overall p<0.0001). These data suggest that in-stent neointimal proliferation is more likely to occur in stented coronary arteries with a more oval than rounded cross-section, and particularly within the more pronounced and curved portion of the oval.

A 13-year-old boy [corrected] underwent heart transplantation for severe congestive heart failure due to dilated cardiomyopathy possibly caused by fulminant acute myocarditis. He suddenly suffered chest discomfort and loss of consciousness during running, and was referred to a hospital with cardiogenic shock. Electrocardiography showed ventricular tachycardia and echocardiography revealed severe hypokinesis in an extensive area of the left ventricular wall with markedly decreased left ventricular ejection fraction. Percutaneous cardiopulmonary support, intraaortic balloon pumping and artificial respiration were performed. He suffered from severe heart failure with septic shock and bleeding tendency. A left ventricular assist system was fitted at 73 days after onset, and he was transferred to the National Cardiovascular Center on the 119th hospital day. At 319 days after the left ventricular assist system operation, heart transplantation was performed. The etiology and treatment for severe heart failure, and several social problems which occurred during care for heart transplantation are discussed.

The aim of this study was to examine the interaction of acute atrial fibrillation (Af) and acute myocardial infarction (AMI) on left atrial (LA) and left ventricular (LV) filling in atrioventricular (A-V) sequential paced, open chest, anesthetized dogs. Left atrial conduit function was determined from pulmonary venous flow (PVF) and detailed analysis of early diastolic flow with the use of micromanometers and transmitral Doppler echocardiography. We studied 8 dogs with regular ventricular rates to avoid the confounding effect of ventricular arrhythmia in Af. In the control stage, Af increased the diastolic PVF volume to the left atrium compared with that during regular A-V pacing (from 0.58 +/- 0.11 mL/beat to 0.70 +/- 0.13 mL/beat, P <.05), as a compensatory response to the impaired systolic PVF volume (from 0.56 +/- 0.12 mL/beat to 0.41 +/- 0.11 mL/beat, P <.05). As a result, cardiac output was maintained. However, in the AMI stage, Af decreased cardiac output (from 0.95 +/- 0.32 L/min to 0.80 +/- 0.23 L/min, P <.05 versus AMI with A-V pacing), and decreased diastolic PVF volume (from 0.46 +/- 0.13 mL/beat to 0.33 +/- 0.14 mL/beat, P <.05 versus AMI with A-V pacing). These changes were associated with a prolonged LV isovolumic pressure decay rate. Our study demonstrates that Af does not affect cardiac output in the setting of normal LV function at a controlled ventricular rate because enhanced LA conduit flow compensates for impaired LA reservoir function. In contrast, in the setting of AMI, the compensatory response to Af is attenuated because of abnormal LV relaxation, resulting in a decrease in cardiac output.

Background: The thickness of the fibrous cap is a major determinant in the vulnerability of atherosclerotic plaque to rupture. It has been demonstrated that intravascular ultrasound (IVUS) backscatter from fibrous tissue is strongly dependent on the ultrasound beam angle of incidence. This study investigated the feasibility of using a new IVUS color mapping technique representing the angle-dependent echo-intensity variation to determine the thickness of the fibrous cap in atherosclerotic plaque., Methods and Results: Nineteen formalin-fixed noncalcified human atherosclerotic plaques from necropsy were imaged in vitro with a 30-MHz IVUS catheter. The IVUS catheter was moved coaxially relative to the plaque. The images showing maximum and minimum echo intensity of the plaque surface were selected to calculate the angle-dependent echo-intensity variation. A colorized representation of the echo-intensity variation in the plaque was obtained from the 2 IVUS images. A clearly bordered area with large variation in echo intensity was revealed for each plaque surface in the colorized IVUS image. The thickness (x, mm) of this area correlated significantly with that of fibrous cap (y, mm) measured from histologically prepared sections as y=1.05x-0.01 (r=0.81, P:<0.0001). Bland-Altman analysis also supported the reliability of this method (mean difference, 0.00+/-0.10 mm)., Conclusions: This novel technique for color mapping the echo-intensity variation in IVUS provided an accurate representation of the thickness of the fibrous cap in atherosclerotic plaque. This method may be useful in assessing plaque vulnerability to rupture in atherosclerosis.