Background Studies on the efficacy of prescription omega-3 polyunsaturated fatty acids to reduce cardiovascular events have produced conflicting results. Research design and methods This 3-year prospective post-marketing surveillance study evaluated the effect of omega-3-acid ethyl esters (O3AEE; usual dosage 2 g/day) on cardiovascular events in high-risk statin-treated Japanese patients with hypertriglyceridemia. Statin-treated patients not receiving O3AEE were included as a reference cohort. The composite primary endpoint was cardiovascular death, myocardial infarction, stroke, angina requiring coronary revascularization, or peripheral arterial disease requiring surgery or peripheral arterial intervention. Results At 3 years, Kaplan-Meier estimated cumulative incidence of the primary endpoint was 2.5% (95% confidence interval, 2.1%-2.9%) in O3AEE-treated patients (N = 6,580) and 2.7% (2.4%-3.1%) in non-O3AEE-treated patients (N = 7,784; hazard ratio, 0.99; 95% confidence interval, 0.79-1.23). Incidence of heart failure requiring hospitalization was 0.4% with O3AEE versus 0.8% in non-O3AEE-treated patients (hazard ratio, 0.47; 95% confidence interval, 0.28-0.78; P < 0.05). Conclusions Among patients receiving statins, cardiovascular event incidence did not differ significantly between O3AEE-treated patients and non-O3AEE-treated patients. Further studies are required before definitive conclusions can be drawn on the effect of O3AEE on cardiovascular event incidence in high-risk patients with hypertriglyceridemia.

In 2019, the Japanese Circulation Society published 2 guidelines in the field of coronary artery disease (CAD): (1) a guideline for acute coronary syndrome (ACS) that integrated guidelines for ST-elevation acute myocardial infarction, non-ST-elevation ACS (NSTE-ACS), and secondary prevention for myocardial infarction, and (2) guideline for revascularization of stable CAD by coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI).1,2 These guidelines were substantially revised to reflect the latest evidence, but after publication of the revised guidelines, important new evidence was reported and new concepts have been established. In particular, important evidence has accumulated about antithrombotic therapy after PCI that is directly related to daily clinical practice. Therefore, we are providing an update focusing on this area without waiting for the next revision of the entire guideline. Because the risk of bleeding events is higher and the risk of thrombotic events is lower in East Asian patients, the risk/benefit balance between thrombosis and bleeding in East Asian patients is suggested to be different from that in other populations.3,4 In fact, lowerdose antithrombotic therapy is recommended in East Asia compared with Western countries, and a lower target value for the international standardized ratio of prothrombin time (PT-INR) is also recommended for elderly patients. For these reasons, extrapolation of evidence from the USA and Europe requires careful consideration, and verification by assessment in clinical practice in Japan is always necessary. In this regard, the present update includes clinical trials performed in Japan and the data from these trials played a major role in the preparation of the guideline update. This guideline update also covers patients who are managed conservatively with drug therapy, in addition to those who have undergone reperfusion therapy and

Background: The mechanisms responsible for the more rapid progression of aortic stenosis (AS) in patients with bicuspid aortic valve (BAV) than in those with tricuspid aortic valve (TAV) are unknow...

Background: We have previously reported the usefulness of our newly developed visual aortic stenosis (AS) score in screening for AS using pocket-sized echocardiography. The objective of this study was to investigate whether the visual AS score and/or conventional aortic valve calcification score derived from pocket-sized echocardiography can be used to predict AS-related events.Methods: One hundred and nine patients with systolic ejection murmur (SEM) or known AS (64 males, age 75 +/- 9 years) were enrolled and a visual AS score and an aortic valve calcification score were assessed using pocket-sized echocardiography. The primary endpoint was defined as AS-related events, including cardiac death and aortic valve replacement, during the follow-up period.Results: In a multivariate Cox proportional hazards analysis, AS-related events were independently predicted by an aortic valve calcification score >= 3 (HR, 3.5; 95% CI, 1.1-11; p = 0.033) and a visual AS score >= 3 (HR, 15; 95% CI, 1.8-125; p = 0.013). During 18 +/- 9 months of follow-up, the event-free survival rate was 98% in patients with both a visual AS score <3 and an aortic valve calcification score <3, 90% in patients with either a visual AS score >= 3 or an aortic valve calcification score >= 3 (p < 0.0001), and 62% in patients with both a visual AS score >= 3 and an aortic valve calcification score >= 3 (p < 0.0001).Conclusions: The combination of visual AS score and aortic valve calcification score derived from pocket sized echocardiography is useful for predicting AS-related events in patients with SEM. (C) 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

OBJECTIVES The purpose of this study was to clarify the prognostic significance of diagnosing whether the failing heart is functioning on the descending limb of the Starling curve by using echocardiography with passive leg lifting (PLL).BACKGROUND Patients with advanced heart failure can shift to the descending limb of the Starling curve, in which pre-load does not lead to an expected increase in forward left ventricular stroke volume (LVSV).METHODS Thirty-five consecutive patients with left ventricular (LV) ejection fraction of < 40% underwent echocardiography at rest during baseline and during PLL to increase pre-load.RESULTS Despite PLL, a paradoxical decrease in forward LVSV was observed in 15 (43%) patients. Changes in forward LVSV inversely correlated with those in functional mitral regurgitation (r = -0.56). The primary endpoint of cardiac death or hospitalization due to worsening heart failure occurred in 15 (43%) patients during follow-up (2.8 +/- 2.2 years). There were a number of significant predictors of the primary endpoint in the univariate Cox analysis: baseline E/A ratio (p = 0.0002), paradoxical decrease in LVSV despite PLL (hazard ratio: 4.44; 95% confidence interval: 1.41 to 14.0; p = 0.011), baseline LV end-systolic volume (p = 0.023), and baseline LV ejection fraction (p = 0.034). In the bivariate Cox analysis, an addition of the paradoxical decrease in LVSV significantly enhanced the predictive power of all other univariate predictors.CONCLUSIONS Heart failure patients with LV systolic dysfunction on the descending limb of the Starling curve can be recognized by the paradoxical decrease in LVSV despite PLL, and the prognostic predicting power is additive to the other traditional echocardiographic predictors. Also, our results suggest that functional mitral regurgitation is an important reason for the descending limb of the Starling curve, which is clinically recognized as the pre-load-induced decrease in forward LVSV. (C) 2017 by the American College of Cardiology Foundation.

For future space infrared astronomical coronagraphy, we perform experimental studies on the application of aluminum mirrors to a coronagraph. Cooled reflective optics is required for broad-band mid-infrared observations in space, while high-precision optics is required for coronagraphy. For the coronagraph instrument originally proposed for the next-generation infrared astronomical satellite project SPICA (SCI: SPICA Coronagraph Instrument), we fabricated and evaluated the optics consisting of high-precision aluminum off-axis mirrors with diamond-turned surfaces, and conducted a coronagraphic demonstration experiment using the optics with a coronagraph mask. We first measured the wave front errors (WFEs) of the aluminum mirrors with a He-Ne Fizeau interferometer to confirm that the power spectral densities of the WFEs satisfy the SCI requirements. Then we integrated the mirrors into an optical system and evaluated the overall performance of the system. As a result, we estimate the total WFE of the optics to be 33 nm (rms), each mirror contributing 10-20 nm (rms) for the central 14 mm area of the optics, and obtain a contrast of 10^(-5.4) as a coronagraph in the visible light. At a wavelength of 5 um, the coronagraphic system is expected to achieve a contrast of ~10^(-7) based on our model calculation with the measured optical performance. Thus our experiment demonstrates that aluminum mirror optics is applicable to a highly WFE-sensitive instrument such as a coronagraph in space.

We present the design, fabrication and test results for a dichroic mirror, which was primarily developed for the SPICA Coronagraph Instrument (SCI), but is potentially useful for various types of astronomical instrument. The dichroic mirror is designed to reflect near- and mid-infrared but to transmit visible light. Two designs, one with 3 layers and one with 5 layers on BK7 glass substrates, are presented. The 3-layer design, consisting of Ag and ZnS, is simpler, and the 5-layer design, consisting of Ag and TiO2 is expected to have better performance. Tape tests, evaluation of the surface figure, and measurements of the reflectivity and transmittance were carried out at ambient temperature in air. The reflectivity obtained from measurements made on mirrors with 5 layers were > 80 % for wavelengths, lambda, from 1.2 to 22 mu m and > 90 % for lambda from 1.8 to 20 mu m. The transmittance obtained from measurements made on mirrors with 5 layers were > 70 % for lambda between 0.4 and 0.8 mu m. Optical ghosting is estimated to be smaller than 10(-4) at lambda > 1.5 mu m. A protective coating for preventing corrosion was applied and its influence on the reflectivity and transmittance evaluated. A study examining the trade-offs imposed by various configurations for obtaining a telescope pointing correction signal was also undertaken.

Background: The development of aortic valve stenosis (AS) involves multiple events, including inflammation and lipid deposition and oxidation. Circulating levels of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) play an important role in the development and progression of atherosclerosis. The aims of this study were to investigate the serum levels of sLOX-1 in patients with AS and also examine the expression of LOX-1 immunohistochemically in aortic valve specimens from these patients. Methods: Serum sLOX-1 levels were measured in patients with AS (n=128), stable angina pectoris (SAP, n=343) and in 53 control subjects using a sandwich ELISA method. Frozen aortic valve samples were also obtained surgically from a cohort of 20 AS patients. In addition, frozen aortic valve specimens were obtained at autopsy from individuals who died of non-cardiovascular causes (n = 11, mean age 68 yr) as a reference. Immunostaining of the samples was performed using antibodies against smooth muscle cells, macrophages, T-lymphocytes, neutrophils, microvessels, and LOX-1. Results: Serum sLOX-1 levels were significantly higher in AS patients compared with SAP patients ( P <0.0005) or control subjects ( P <0.0001). There were no differences in serum sLOX-1 levels between AS patients with or without coronary artery disease. Immunohistochemical staining showed that the LOX-1-positive area, as a percentage of the total area, was significantly (P<0.01) higher in AS patients compared with reference cases. Double immunostaining for LOX-1 and macrophages revealed that the vast majority of LOX-1-positive cells were macrophages. Conclusions: This study demonstrates for the first time that serum sLOX-1 levels are elevated in patients with AS, and AS lesions contain a significantly higher percentage of LOX-1-positive macrophages. These findings suggest that LOX-1, a marker of oxidative stress, may play an important role in the development of aortic valve stenosis.

Background: It is well established there is an inverse relationship between high-density lipoprotein (HDL) cholesterol and the risk for coronary artery disease, with its antioxidant properties attributed mainly to the HDL-bound enzyme, paraoxonase-1 (PON-1). We reported that plasma levels of myeloperoxidase, a pro-oxidant enzyme released from activated neutrophils that alters the atheroprotective function of HDL to a dysfunctional form, has a significant inverse correlation with PON-1 levels, especially in female patients with stable angina pectoris (SAP) (Atherosclerosis, 231, 308-314, 2013). Drug-eluting stents (DES) reduce the rate of restenosis, although recurrent angina and repeat revascularization remain major limitations. We investigated whether PON-1 levels predict cardiovascular events in patients with SAP undergoing DES implantation. Methods: Serum PON-1 concentration and activity were measured on admission in 191 SAP patients and 99 control subjects. We also assessed the prognostic significance...

Background: We previously demonstrated that inflammatory biomarkers such as myeloperoxidase (MPO), a member of the heme peroxidase superfamily, and neopterin (produced by activated macrophages after interferon-γ stimulation by T-lymphocytes) are important in the pathogenesis of coronary plaque instability. Additional evidence supports high sensitivity C-reactive protein (hs-CRP) as an independent predictor of increased coronary risk. We assessed the prognostic significance of plasma MPO and neopterin levels, and serum hs-CRP levels in patients with stable angina pectoris (SAP) and unstable angina pectoris (UAP). Methods: Plasma MPO, neopterin, and serum hs-CRP levels were measured in 219 SAP patients and 144 UAP patients at admission. Cardiovascular (CV) events were defined as sudden cardiac death, fatal or non-fatal myocardial infarction and other non-fatal events including unstable angina pectoris or coronary revascularization. Results: Over a mean follow-up of 27±14 months, 56 SAP patients (26%) had CV events. When SAP patients were stratified based on the median neopterin level (15.0 nmol/L), Kaplan-Meier analysis showed that the high-neopterin group (>15.0 nmol/L) had significantly worse outcomes (P=0.015) than the low-neopterin group. Multivariate analysis showed that elevated neopterin was the only independent factor associated with CV events (OR, 2.19; 95% CI, 1.18-4.09; P=0.014). In contrast, over a mean follow-up of 30±24 months, 33 UAP patients (23%) had CV events. When UAP patients were divided based on the median MPO level (16.0 ng/mL), Kaplan-Meier analysis showed that the high-MPO group (>16.0 ng/mL) had significantly worse outcomes (P=0.012) than the low-MPO group. Multivariate analysis showed that elevated MPO was the only independent factor associated with CV events (OR, 2.58; 95% CI, 1.07-6.23; P=0.035). With regard to hs-CRP levels, there were no significant differences in CV events between the two groups according to the median hs-CRP in both SAP and UAP patients. Conclusions: The clinical significance of elevated MPO and neopterin levels as independent predictors of CV events differs depending on the clinical condition of SAP and UAP patients, because of different production mechanisms of these biomarkers.

In this report we describe our development of a prototype inverse-polished mirror for the passive correction of the static and predictable wavefront errors (WFE) of space-based telescopes, in particular, especially for infrared coronagraphs. An artificial WFE pattern with a root mean square (rms) value of 350 nm was numerically generated to facilitate the design of the prototype mirror. The surface of the mirror is approximately flat, is 50.0 mm in diameter and 15.0 mm thick at the edge. The designed WFE pattern was constructed on the mirror surface by micro-polishing. Both the figure and roughness of the mirror surface were evaluated. The rms value of the measured surface figure was reduced to 135 nm after subtraction of the designed surface figure. The benefit of subtraction to mid-infrared coronagraph performance was simulated, which showed the contrast was improved by a factor of ~100 close to the core (closer than 10 λ/D where λ and D are the wavelength and telescope aperture diameter, respectively) of the coronagraphic image of a point source. An analysis of the power spectrum density shows that the lower frequencies in the WFE are well reproduced on the mirror, while the higher frequencies remain due to the limitations imposed on the controllable spatial resolution by the fabrication process. In this study, inverse-polished mirrors combined with deformable mirrors and their application to ground-based telescopes are also discussed. To fully explore the potential of the inverse-polished mirror, a systematic allocation of the error budget is essential taking into account not only the fabrication accuracy of the mirror but also an evaluation of the telescope and other factors with non-predictable uncertainties.

Background: Pocket-sized echocardiography may serve as an initial tool to screen for aortic stenosis (AS). The purpose of this study was to evaluate the usefulness of a novel and simple method using pocket-sized echocardiography to screen for AS.Methods: Subjects (n = 130) with systolic ejection murmur or known AS were studied. After physical examination, each aortic cusp's opening was visually scored using pocket-sized echocardiography as follows: 0 = not restricted, 1 = restricted, or 2 = severely restricted. The sum of the scores was defined as the visual AS score. On the basis of high-end echocardiography, an aortic valve area index <0.60 cm(2)/m(2) and an aortic valve area index of 0.60 to 0.85 cm(2)/m(2) were considered to indicate severe and moderate AS, respectively.Results: For diagnosing severe AS (n = 27), a visual AS score >= 4 had sensitivity of 85% and specificity of 89%. For diagnosing moderate to severe AS (n = 57), a visual AS score >= 3 had sensitivity of 84% and specificity of 90%. The areas under the receiver operating characteristic curves for diagnosing severe and moderate to severe AS with a visual AS score (0.946 and 0.936, respectively) were slightly larger than those for a skilled physical examination (0.917 and 0.898, respectively) (P = NS for both) but were significantly larger than for an aortic valve calcification score also obtained using pocket-sized echocardiography (areas under the curve, 0.816 [P = .0015] and 0.827 [P = .0001], respectively).Conclusions: A novel and simple method using pocket-sized echocardiography is useful for rapid grading of AS in subjects with systolic ejection murmur.

Objectives This study sought to investigate the association between pathological characteristics of aspirated intracoronary thrombi and the incidence of angiographically visible distal embolization (AVDE) during primary percutaneous coronary intervention (p-PCI) in patients with ST-segment elevation myocardial infarction (STEMI) treated with thrombus aspiration.Background AVDE of atherosclerotic and thrombotic material has been shown to impair myocardial perfusion and contribute to poor clinical outcome in patients with STEMI. Recent studies have shown that thrombus composition and size are associated with the incidence of AVDE.Methods Aspirated thrombi from 164 STEMI patients within 12 h of symptom onset were investigated immunohistochemically using antibodies against platelets, erythrocytes, and inflammatory cells.Results The angiographic results showed that AVDE during p-PCI occurred in 22 (13.4%) patients. Pathological analysis revealed that thrombi from patients with AVDE had a greater erythrocyte-positive area (60 +/- 15% vs. 43 +/- 21%, p < 0.0005) and more myeloperoxidase-positive cells (943 +/- 324 cells/mm(2) vs. 592 +/- 419 cells/mm(2), p < 0.0005) than those from patients without AVDE. Thrombus size, quantified as the thrombus surface area, was positively correlated with the erythrocyte component (r = 0.362, p < 0.0001). Moreover, multivariate logistic analysis demonstrated that erythrocyte-positive area in the thrombi, glucose levels on admission, larger vessel diameter (>= 3.5 mm), and pre-balloon dilation were independent predictors of the incidence of AVDE.Conclusions This study demonstrated that the erythrocyte-rich component of aspirated thrombi may be associated with the incidence of AVDE during p-PCI in patients with STEMI. (J Am Coll Cardiol Intv 2013;6:377-85) (C) 2013 by the American College of Cardiology Foundation

Inflammation and oxidative stress play key roles in atherosclerotic plaque instability, and plaque rupture/erosion and subsequent thrombus formation constitute the principal mechanisms of total vessel occlusion and acute ST-elevation myocardial infarction (STEMI). Plaque disruption triggers the formation of initial platelet aggregates that grow in association with an increase in fibrin formation, leading to persistent coronary flow obstruction and blood coagulation. The fibrin network may trap large numbers of erythrocytes and inflammatory cells to form an erythrocyte-rich thrombus. In fact, previous clinical studies have shown that not only platelet-rich white thrombi, but also erythrocyte-rich red thrombi can be visualized using angioscopy in patients with acute coronary syndrome. Recently, the development of thrombus aspiration and distal protection devices has significantly improved the clinical outcomes of percutaneous intervention in STEMI patients and has enabled the evaluation of antemortem coronary artery thrombi. This is important because previous autopsy studies were unable to differentiate coronary thrombi responsible for myocardial ischemia from postmortem clots. Using frozen samples of aspirated thrombi and specific monoclonal antibodies, we investigated the cellular components of thrombi (platelets, erythrocytes, fibrin and inflammatory cells, such as myeloperoxidase-positive cells) and pathologically evaluated the relationships between erythrocyterich thrombi and inflammation, oxidative stress and clinical outcomes in STEMI patients. Therefore, this review article focuses on the efficacy of thrombus aspiration therapy and the components of aspirated intracoronary thrombi in STEMI patients and presents the results of recent studies regarding the relationship between the composition of aspirated intracoronary thrombi and clinical outcomes.

End-stage renal disease (ESRD) patients undergoing hemodialysis (HD) have a high prevalence of cardiovascular events. Low-density lipoprotein (LDL) in dialysis patients has been shown to be susceptible to in vitro peroxidation; therefore, oxidized-LDL (ox-LDL) could be generated in these patients. Moreover, myeloperoxidase (MPO) released from activated neutrophils may play a role in the induction of LDL oxidation. The purpose of this study was to investigate the relationship between plasma ox-LDL levels, plasma MPO levels, and serum high-sensitivity C-reactive protein (hs-CRP) levels during initial HD in patients with diabetic ESRD. Patients (n=28) had serial venous blood samples drawn before and after HD at the initial, second, and third sessions. Plasma ox-LDL levels were measured using a specific monoclonal antibody (DLH3), and plasma MPO levels were measured using an enzyme-linked immunosorbent assay kit. Plasma ox-LDL levels and MPO levels after a single HD session increased significantly (ox-LDL, P<0.005; MPO, P<0.0001) compared with levels before that HD session. However, the increase was transient since the levels returned to pre-HD session levels. Additionally, plasma MPO levels showed a positive correlation with plasma ox-LDL levels during HD (R=0.62, P=0.0029). No significant change was observed in serum hs-CRP levels before and after each HD session. This study demonstrates that plasma MPO levels are directly associated with plasma ox-LDL levels in diabetic ESRD patients during initial HD. These findings suggest a pivotal role for MPO and ox-LDL in the progression and acceleration of atherosclerosis in patients undergoing HD.