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A 54-year-old man was transferred to our hospital due to congestive heart failure and left ventricular thrombi. Transthoracic echocardiography (TTE) showed mobile "ball-like" not only left ventricular but also right ventricular thrombi associated with severe impaired left and right ventricular function. Contrast-enhanced computed tomography (CT) and cardiac magnetic resonance imaging (MRI) also detected biventricular apical thrombi complicated with right renal infarction. Coronary angiography showed non-significant stenosis. Due to the mobility of thrombi and complication of systemic infarction, the surgical transatrial video-assisted removal of biventricular thrombi was performed and postoperative course has been uneventful over a period of 6 months. Endomyocardial biopsy performed during an operation showed no specific findings such as endomyocarditis, indicating the diagnosis of dilated cardiomyopathy (DCM). This is a rare case of DCM complicated with biventricular apical thrombi detected clearly by multimodality imaging such as TTE, contrast-enhanced CT and cardiac MRI, and surgical removal was performed successfully. .

A 72-year-old man underwent video-assisted thoracoscopic left upper lobectomy for small cell lung cancer. After 16 days, he experienced epigastric abdominal pain and vomiting, and was taken by ambulance to our hospital. Contrast-enhanced computed tomography (CT) showed a propagation of thrombus in the stump of the left superior pulmonary vein (LSPV) complicated with splenic infarction. The patient received anticoagulation therapy with heparin and warfarin, and further progression of the thrombus or any systemic embolic event was not observed during hospitalization. Here, we report a patient presenting with LSPV thrombosis complicated with splenic infarction after video-assisted thoracoscopic surgery (VATS), and describe several months follow-up CT imaging results after administration of an oral anticoagulation therapy.

A high prevalence and a rapid progression of aortic valve stenosis (AS) in patients undergoing hemodialysis (HD) has been reported. In these circumstances, intraleaflet hemorrhage of aortic valve may be related to the development of AS in HD patients. We immunohistochemically examined the relationship among intraleaflet hemorrhage, neovascularization, hemoglobin scavenger receptor (CD163), and heme oxygenase-1 (HO-1) using surgically resected aortic valve specimens from AS patients undergoing HD. The study population consisted of 26 HD patients and 25 non-HD patients with severe AS who had undergone aortic valve replacement. Frozen aortic valve samples surgically obtained from AS patients were stained immunohistochemically with antibodies against smooth muscle cells, macrophages, glycophorin-A (a protein specific to erythrocyte membranes), CD31, CD163, and HO-1. Morphometric analysis demonstrated that the CD163-positive macrophage score, the number of CD31-positive microvessels, and the percentage of glycophorin-A and HO-1-positive area were significantly higher in HD patients than in non-HD patients (CD163-positive macrophage score, P

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

Low high-density lipoprotein (HDL) cholesterol is well-established as a negative risk factor for coronary artery disease (CAD) and its anti-oxidant property has been attributed mainly to the HDL-bound enzyme paraoxonase-1 (PON-1). Recently, myeloperoxidase (MPO), a pro-oxidant enzyme released from activated neutrophils, has been shown to alter the atheroprotective function of HDL to a dysfunctional form. This study investigated the relationship between plasma MPO and serum PON-1 levels in patients with stable (SAP) and unstable angina pectoris (UAP). Plasma MPO levels and serum PON-1 concentration/activity were measured in patients with SAP (n = 226), UAP (n = 151) and in control subjects (n = 99). Plasma MPO levels in UAP patients were significantly higher than those in SAP patients or in control subjects (UAP, 21.6[16.7-44.6]; SAP, 19.3[15.7-29.1]; control, 15.9[14.7-18.7] ng/mL; P < 0.0001). Serum PON-1 concentrations in UAP and SAP patients were significantly lower than those in control subjects (UAP, 55.6[45.9-69.7]; SAP, 55.0[46.9-64.9]; control, 62.5[51.1-78.8] μg/mL; P = 0.0002). Plasma MPO levels showed a weak inverse correlation with serum PON-1 concentrations in all subjects (R = -0.163, P < 0.0005). Moreover, in women, plasma MPO levels showed a significant inverse correlation with serum PON-1 concentrations and PON-arylesterase activity in SAP (concentration: R = -0.537, P < 0.0001; arylesterase-activity: R = -0.469, P < 0.001) and UAP (concentration: R = -0.340, P < 0.05; arylesterase-activity: R = -0.350, P < 0.05) patients, but not in men. This study demonstrates that plasma MPO levels have a significant inverse correlation with PON-1 levels, especially in women, in SAP and UAP patients, and suggests that an imbalance between pro-oxidants and anti-oxidants may contribute to the progression of coronary plaque instability

ObjectivesThis 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.BackgroundAVDE 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.MethodsAspirated thrombi from 164 STEMI patients within 12 h of symptom onset were investigated immunohistochemically using antibodies against platelets, erythrocytes, and inflammatory cells.ResultsThe 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/mm2 vs. 592 ± 419 cells/mm2, 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.ConclusionsThis 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.

Background— Balloon pulmonary angioplasty (BPA) is an alternative therapy for patients with chronic thromboembolic pulmonary hypertension who are ineligible for standard therapy, pulmonary endarterectomy. Although there are several classifications of vascular lesions, these classifications are based on the features of the specimen removed during pulmonary endarterectomy. Because organized thrombi are not removed during balloon pulmonary angioplasty, we attempted to establish a new classification of vascular lesions based on pulmonary angiographic images. We evaluated the success and complication rate of BPA in accordance with the location and morphology of thromboembolic lesions. Methods and Results— We reviewed 500 consecutive procedures (1936 lesions) of BPA in 97 patients with chronic thromboembolic pulmonary hypertension and investigated the outcomes of BPA based on the lesion distribution and the angiographic characteristics of the thromboembolic lesions, as follows: type A, ring-like stenosis lesion; type B, web lesion; type C, subtotal lesion; type D, total occlusion lesion, and type E, tortuous lesion. The success rate was higher, and the complication rate was lower in ring-like stenosis and web lesions. The total occlusion lesions had the lowest success rate. Tortuous lesions were associated with a high complication rate and should be treated only by operators with extensive experience with BPA. Conclusions— We modified the previous angiographic classification and established a new classification for each vascular lesion. We clarified that the outcome and complication rate of the BPA are highly dependent on the lesion characteristics.

Oxidative stress has been implicated in the pathogenesis of heart failure. Reactive oxygen species (ROS) are produced in the failing myocardium, and ROS cause hypertrophy, apoptosis/cell death and intracellular Ca(2+) overload in cardiac myocytes. ROS also cause damage to lipid cell membranes in the process of lipid peroxidation. In this process, several aldehydes, including 4-hydroxy-2-nonenal (HNE), are generated and the amount of HNE is increased in the human failing myocardium. HNE exacerbates the formation of ROS, especially H₂O₂ and ·OH, in cardiomyocytes and subsequently ROS cause intracellular Ca(2+) overload. Treatment with beta-blockers such as metoprolol, carvedilol and bisoprolol reduces the levels of oxidative stress, together with amelioration of heart failure. This reduction could be caused by several possible mechanisms. First, the beta-blocking effect is important, because catecholamines such as isoproterenol and norepinephrine induce oxidative stress in the myocardium. Second, anti-ischemic effects and negative chronotropic effects are also important. Furthermore, direct antioxidative effects of carvedilol contribute to the reduction of oxidative stress. Carvedilol inhibited HNE-induced intracellular Ca(2+) overload. Beta-blocker therapy is a useful antioxidative therapy in patients with heart failure.

Despite the use of statin therapy and achieving the target for low-density lipoprotein cholesterol, a substantial number of coronary events are not prevented, and residual risk factors remain unsettled. Recently, ezetimibe has been shown to reduce not only low-density lipoprotein cholesterol but also triglyceride (TG) levels. The aim of this study was to investigate the associations of residual risk factors, mainly hypertriglyceridemia, with endothelial function during statin therapy in patients with coronary heart disease and examine the effect of ezetimibe add-on therapy. A total of 109 consecutive patients with coronary heart disease during statin therapy were enrolled. Lipid profile was measured and endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery in a fasting state. Next, 32 patients with high TG levels (≥150 mg/dl) were prospectively assigned to the ezetimibe add-on group or the no-ezetimibe group, and endothelial function was assessed after 3 months. Multivariate linear regression analysis demonstrated that serum TG and high-density lipoprotein cholesterol levels were independent determinants of percentage FMD (β = -0.210 and 0.208, respectively, p0.05). In patients with high TG levels, ezetimibe add-on therapy significantly improved percentage FMD (from 3.3 ± 1.1% to 4.0 ± 1.1%, p0.005), whereas no significant change was observed in the no-ezetimibe group. Moreover, the improvement in percentage FMD was significantly associated with reduction in serum TG levels (β = -0.387, p0.05) independent of the change in serum low-density lipoprotein cholesterol levels. In conclusion, hypertriglyceridemia is independently associated with endothelial dysfunction in patients with coronary heart disease during statin therapy. Ezetimibe add-on therapy improves endothelial function in these high-risk populations.

Previous studies have shown that oxidative stress and endothelial dysfunction are related to impaired myocardial microcirculation after reperfusion. Moreover, elevated myeloperoxidase (MPO) levels are associated with endothelial dysfunction. Plasma MPO levels were measured in patients with ST-segment elevation acute myocardial infarction (n = 160) who had undergone percutaneous coronary stenting within 12 hours of symptom onset. We investigated whether the plasma MPO level at admission was associated with impaired myocardial microcirculation, as indicated by ST-segment resolution and myocardial blush grade after reperfusion, and left ventricular ejection fraction and remodeling at 6 months. The patients were divided into 2 groups according to the median MPO value for the entire cohort (low-MPO group < or =50 ng/ml, n = 80; high-MPO group >50 ng/ml, n = 80). ST-segment resolution and the myocardial blush grade were significantly lower in the high-MPO than in the low-MPO group (48 +/- 27% vs 61 +/- 24%, p

Summary Objectives The purpose of this study was to explore the possibility of using our novel echocardiographic index of inefficient left ventricular (LV) contraction in patient selection for cardiac resynchronization therapy (CRT). Methods Forty consecutive patients with LV ejection fraction ≤35% were divided into 2 groups, 9 CRT candidates and 31 non-CRT candidates based on conventional criteria. A global LV time–area curve and regional LV time–area curves in 6 radial sectors were obtained using two-dimensional echocardiography in the short-axis view with speckle tracking. Fractional inefficient contraction (FIC, %) was calculated as follows: (1 − global LV area change/sum of regional LV area changes) × 100. LV dyssynergy and dyssynchrony were quantified as the standard deviations of minimal values of circumferential speckle-tracking strain and their timings in the 6 sectors, respectively. Results There was no significant difference in LV dyssynchrony between CRT candidates and non-CRT candidates (79 ± 61 ms vs. 58 ± 26 ms, respectively). In contrast, FIC was significantly larger in CRT candidates than in non-CRT candidates (15.7 ± 11.0% vs. 5.4 ± 3.5%, respectively, p = 0.0018), with less overlap between groups. FIC showed a positive correlation with dyssynchrony (r = 0.64) and a negative correlation with dyssynergy (r = −0.42). Conclusions Our novel echocardiographic index of inefficient LV contraction, which increases with more dyssynchrony or less dyssynergy, may prove more useful in patient selection for CRT than other indices that focus on LV temporal dyssynchrony alone.

Statin therapy targeting reduction of low-density lipoprotein cholesterol (LDL-C) decreases the risk of coronary heart disease (CHD) and all-cause mortality. However, a substantial number of cases of CHD are not prevented and residual risk factors remain unsettled. A high triglyceride (TG) level is considered to be an important and residual risk factor. Postprandial hyperlipidemia is a condition in which TG-rich chylomicron remnants are increased during the postprandial period and hypertriglycedemia is protracted. Postprandial hyperlipidemia evokes atherogenesis during the postprandial period. Several prospective studies have revealed that nonfasting serum TG levels predict the incidence of CHD. Values of TG, remnant lipoprotein cholesterol, and remnant lipoprotein TG after fat loading were significantly higher in diabetes patients with insulin resistance than in diabetes patients without insulin resistance. Endothelial dysfunction is an initial process of atherogenesis and it contributes to the pathogenesis of CHD. Postprandial hyperlipidemia (postprandial hypertriglyceridemia) is involved in the production of proinflammatory cytokines, recruitment of neutrophils, and generation of oxidative stress, resulting in endothelial dysfunction in healthy subjects, hypertriglyceridemic patients, or type 2 diabetic patients. Effective treatment has not been established till date. Ezetimibe or omega-3 fatty acids significantly decrease postprandial TG elevation and postprandial endothelial dysfunction. Ezetimibe or omega-3 fatty acids added to statin therapy reduce serum TG levels and result in good outcomes in patients with CHD. In conclusion, postprandial hyperlipidemia is an important and residual risk factor especially in patients with insulin resistance syndrome (metabolic syndrome) and diabetes mellitus. Further studies are needed to establish effective treatment.

There has been no previous prospective study evaluating dual antiplatelet therapy (DAPT) duration shorter than 6 months after cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation. STOPDAPT trial is a prospective multi-center single-arm study evaluating 3-month DAPT duration after CoCr-EES implantation. The primary endpoint was a composite of cardiovascular death, myocardial infarction (MI), stroke, definite stent thrombosis (ST) and TIMI major/minor bleeding at 1 year. Between September 2012 and October 2013, a total of 1525 patients were enrolled from 58 Japanese centers, with complete 1-year follow-up in 1519 patients (99.6 %). Thienopyridine was discontinued within 4 months in 1444 patients (94.7 %). The event rates beyond 3 months were very low (cardiovascular death: 0.5 %, MI: 0.1 %, ST: 0 %, stroke: 0.7 %, and TIMI major/minor bleeding: 0.8 %). Cumulative 1-year incidence of the primary endpoint was 2.8 % [upper 97.5 % confidence interval (CI) 3.6 %], which was lower than the pre-defined performance goal of 6.6 % (P

Vascular medial calcification is often observed in patients with arteriosclerosis. It is also associated with systolic hypertension, wide pulse pressure, and fluctuation of blood pressure, which results in cardiovascular events. Eicosapentaenoic acid (EPA) has been shown to suppress vascular calcification in previous animal experiments. We investigated the inhibitory effects of EPA on Wnt signaling, which is one of the important signaling pathways involved in vascular calcification. Intake of food containing 5% EPA resulted in upregulation of the mRNA expression of Klotho, an intrinsic inhibitor of Wnt signaling, in the kidneys of wild-type mice. Expression levels of β-catenin, an intracellular signal transducer in the Wnt signaling pathway, were increased in the aortas of Klotho mutant (kl/kl) mice compared to the levels in the aortas of wild-type mice. Wnt3a or BIO, a GSK-3 inhibitor that activates β-catenin signaling, upregulated mRNA levels of AXIN2 and LEF1, Wnt signaling marker genes, and RUNX2 and BMP4, early osteogenic genes, in human aorta smooth muscle cells. EPA suppressed the upregulation of AXIN2 and BMP4. The effect of EPA was cancelled by T0070907, a PPARγ inhibitor. The results suggested that EPA could suppress vascular calcification via the inhibition of Wnt signaling in osteogenic vascular smooth muscle cells via PPARγ activation.

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 P 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: 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.

A high prevalence and a rapid progression of aortic valve stenosis (AS) in patients undergoing hemodialysis (HD) has been reported. In these circumstances, intraleaflet hemorrhage of aortic valve may be related to the development of AS in HD patients. We immunohistochemically examined the relationship among intraleaflet hemorrhage, neovascularization, hemoglobin scavenger receptor (CD163), and heme oxygenase-1 (HO-1) using surgically resected aortic valve specimens from AS patients undergoing HD. The study population consisted of 26 HD patients and 25 non-HD patients with severe AS who had undergone aortic valve replacement. Frozen aortic valve samples surgically obtained from AS patients were stained immunohistochemically with antibodies against smooth muscle cells, macrophages, glycophorin-A (a protein specific to erythrocyte membranes), CD31, CD163, and HO-1. Morphometric analysis demonstrated that the CD163-positive macrophage score, the number of CD31-positive microvessels, and the percentage of glycophorin-A and HO-1-positive area were significantly higher in HD patients than in non-HD patients (CD163-positive macrophage score, P 0.0001; CD31-positive microvessels, P 0.0001; glycophorin-A, P 0.0001; HO-1, P 0.0001). Double immunostaining for CD163 or HO-1 and macrophages revealed that the majority of CD163- or HO-1-positive cells were macrophages. Furthermore, CD163-positive macrophage score was positively correlated with glycophorin-A, HO-1-positive area, and the number of CD31-positive microvessels (glycophorin-A, R = 0.66, P 0.0001; HO-1, R = 0.50, P 0.0005; microvessels, R = 0.38, P 0.01). These findings suggest a positive association among intraleaflet hemorrhage, neovascularization, and enhanced expression of CD163 and HO-1 as a response to intraleaflet hemorrhage in stenotic aortic valves in AS patients undergoing HD.

Prolonged dual antiplatelet therapy (DAPT) after coronary stent implantation is associated with higher risk for bleeding. Second-generation drug-eluting stents (G2-DES), cobalt-chromium everolimus-eluting stent (CoCr-EES) in particular, are reported to have lower risk for stent thrombosis (ST)

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 erythrocyte-rich 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, P0.005; MPO, P0.0001) 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.

Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that is induced by intraplaque hemorrhage and degrades free heme and releases ferrous iron, which is rapidly sequestered by ferritin. In vitro studies have shown that binding of hemoglobin to hemoglobin scavenger receptor (CD163) induces HO-1 and the anti-inflammatory mediator interleukin (IL)-10. We immunohistochemically examined the relationship between CD163 expression in macrophages and intraplaque hemorrhage, HO-1, IL-10, and ferritin using coronary atherectomy specimens from patients with stable (SAP) or unstable angina pectoris (UAP). A total of 67 patients underwent atherectomy for SAP (n = 33) or UAP (n = 34). Samples were stained with antibodies against smooth muscle cells, macrophages, glycophorin-A (a protein specific to erythrocyte membranes), CD163, HO-1, IL-10, and ferritin. To identify cell types of HO-1-positive cells, double immunostaining was also performed. Double immunostaining for HO-1 and macrophages revealed that the vast majority of HO-1-positive cells were macrophages. Morphometric analysis demonstrated that CD163-positive macrophage score and the percentage of glycophorin-A-, HO-1-, IL-10-, and ferritin-positive areas were significantly higher in UAP than in SAP patients (CD163, P < .005; glycophorin-A, P < .0001; HO-1, P < .0001; IL-10, P < .005; ferritin, P = .0001). Moreover, CD163-positive macrophage score was positively associated with the percentage of glycophorin-A-, HO-1-, IL-10-, and ferritin-positive areas (glycophorin-A, r = 0.60, P < .0001; HO-1, r = 0.67, P < .0001; IL-10, r = 0.45, P < .0005; ferritin, r = 0.61, P < .0001). These findings suggest that enhanced expression of HO-1 and HO-1-related atheroprotective molecules plays an important role in exerting anti-inflammatory, antioxidant, and scavenging functions, which could contribute to plaque stabilization.

Aims Recent studies have demonstrated that erythrocytes are a potential component in atheromatous lesions and thrombus formation in patients with ST-elevation myocardial infarction (STEMI). The purpose of this study was to determine the associations of red blood cell (RBC) component of coronary thrombi with oxidative stress and myocardial reperfusion. Methods and results Aspirated thrombi from 178 STEMI patients within 12 h of symptom onset were investigated immunohistochemically using antibodies against platelets, RBCs, fibrin, macrophages, and neutrophils [myeloperoxidase (MPO)]. The thrombi were divided into tertiles according to the percentage of glycophorin-A-positive area: low (glycophorin-A-positive area

Intermittent arm ischemia before percutaneous coronary intervention induces remote ischemic preconditioning (RIPC) and attenuates myocardial injury in patients with myocardial infarction. Several studies have shown that intermittent arm ischemia increases coronary flow and is related to autonomic nerve system. The aim of this study was to determine whether intermittent arm ischemia induces vasodilatation of other arteries and to assess changes in the autonomic nerve system during intermittent arm ischemia in humans. We measured change in the right brachial artery diameter during intermittent left arm ischemia through three cycles of 5-min inflation (200 mmHg) and 5-min deflation of a blood-pressure cuff using a 10-MHz linear array transducer probe in 20 healthy volunteers. We simultaneously performed power spectral analysis of heart rate. Ischemia-reperfusion of the left arm significantly dilated the right brachial artery time-dependently, resulting in a 3.2 ± 0.4% increase after the 3rd cycle. In the power spectral analysis of heart rate, the high-frequency domain (HF), which is a marker of parasympathetic activity, was significantly higher after the 3rd cycle of ischemia-reperfusion than baseline HF (P = 0.02). Intermittent arm ischemia was accompanied by vasodilatation of another artery and enhancement of parasympathetic activity. Those effects may play an important role in the mechanism of RIPC.

Background Myeloperoxidase (MPO) is a leucocyte enzyme that catalyses the formation of a number of reactive oxidant species. Objective The purpose of this study is to evaluate the relationship between angiographic coronary plaque morphology in patients with unstable angina pectoris (UAP) or stable angina pectoris (SAP) and MPO levels. Patients and design Plasma MPO levels on admission were measured in 236 patients with UAP, 146 with SAP and 85 control subjects using an ELISA kit. The angiographic morphology of the culprit lesion was classified into two types, simple or complex, based on the Ambrose classification. In addition, 61 atherectomy specimens obtained from a different cohort of patients with UAP and SAP were studied immunohistochemically for MPO. Results Median (IQR) plasma MPO levels in patients with UAP with a complex lesion were significantly higher than in patients with a simple lesion (41.9 (21.7-73.7) ng/ml vs 20.5 (15.9-27.9) ng/ml, p

SummaryA 45-year-old man with dilated cardiomyopathy was admitted to our hospital due to congestive heart failure (CHF). Despite the optimal medical treatment, his condition had not improved because of severe left ventricular dysfunction. Because he experienced non-sustained ventricular tachycardia (VT), a biventricular implantable cardioverter-defibrillator (Bi-V ICD) was implanted for reduction of dyssynchrony and primary prevention of lethal tachyarrhythmia. After discharge, he developed CHF and was transported to our hospital by ambulance. In the ambulance, monomorphic sustained VT with 200bpm suddenly occurred. The ICD detected it as fast VT and anti-tachycardia pacing (ATP) was delivered. After the ATP therapy, RR intervals of VT became irregular and prolonged. Ventricular fibrillation-like electrical activity was recorded by a far-field electrogram from the defibrillator, but the tachycardia cycle length exceeded 400ms which is under the tachycardia detection rate. The device failed to deliver a shock and the patient had to be rescued with an external shock. This is a rare case of fast VT that degenerated into undetectable life-threatening tachyarrhythmia by ATP.

SummaryA 52-year-old man experienced acute chest pain and was transferred to our hospital. An electrocardiogram showed ST-segment elevation in leads II, III, aVf, and V1 through V3. The diagnosis at the emergency room was inferior acute myocardial infarction (AMI), and emergent coronary angiography (CAG) was performed. While CAG showed subtotal occlusion of the right coronary artery (RCA) ostium, aortic dissection was suspected due to staining of the contrast agent distal to the occluded site of RCA. Intravascular ultrasound showed compression of the RCA ostium due to aortic dissection. We performed bare metal stent implantation, and contrast-enhanced computed tomography (CT) after stenting showed a thrombosed type A aortic dissection. The patient received medical treatment along with repeated CT and echocardiographic examinations, and was discharged without any events one month after admission. CAG six months after stenting and 64-multislice CT angiography one year later showed a patent RCA. Contrast-enhanced CT at six months showed complete resorption of the ascending aortic intramural hematoma, and 64-multislice CT at one year showed a descending aortic intramural hematoma. The patient is doing well one year after the onset. This is a rare case of successful medical treatment for acute type A aortic dissection complicated with AMI.

Aims Effective clearance of extracellular haemoglobin (Hb) is thought to limit systemic oxidative heme toxicity, which is presumed to contribute to the pathogenesis of plaque instability. We immunohistochemically examined the relationship between intraplaque haemorrhage, 4-HNE (4-hydroxy-2-nonenal), an index of lipid peroxidation, and the Hb scavenger receptor (CD163), using coronary atherectomy specimens from 74 patients with stable angina pectoris (SAP, n = 39) or unstable angina pectoris (UAP, n = 35). Methods and results Atherectomy samples were stained with antibodies against glycophorin A (a protein specific to erythrocyte membranes), CD31, 4-HNE, and CD163. Quantitative analysis demonstrated that glycophorin A-positive areas, 4-HNE-positive macrophage score, and CD163-positive macrophage score in UAP patients were significantly higher (glycophorin A, P < 0.0001; 4-HNE-positive macrophage score, P < 0.0001; CD163-positive macrophage score, P < 0.0005) than in SAP patients. The percentage of the glycophorin A-positive area showed a significant positive correlation with the number of CD31-positive microvessels and the 4-HNE-positive macrophage score (microvessels, R = 0.59, P < 0.0001; 4-HNE, R = 0.59, P < 0.0001). Moreover, the CD163-positive macrophage score was positively correlated with glycophorin A-positive area and the 4-HNE-positive macrophage score (glycophorin A, R = 0.58, P < 0.0001; 4-HNE, R = 0.53, P < 0.0001). Conclusion These findings suggest a positive association among intraplaque haemorrhage, enhanced expression of Hb scavenger receptor, and lipid peroxidation in human unstable plaques.

Percutaneous balloon pericardiotomy and intrapericardial instillation seemed to be less invasive and effective treatments for refractory pericardial effusion. A 65-year-old man who suffered from refractory pericardial effusion associated with gastric cancer and had been hospitalized three times for pericardiocentesis, complained of dyspnea at rest and visited our emergency room. Echocardiography showed a large amount of pericardial effusion all around the heart and signs of cardiac tamponade. Percutaneous balloon pericardiotomy was performed and pericardial effusion turned to pleural effusion. We performed left thoracocentesis. One week later, massive pericardial effusion localized only around the right heart appeared, and pericardiocentesis was performed again. After another month, pericardial effusion around right heart appeared again and intrapericardial instillation with OK-432 (Picibanil) was tried. After the procedure, the pericardial effusion did not increase, and he has had few symptoms for 2 months as an outpatient.

A 60-year-old female had sudden onset of syncope. The emergency service noticed that she suffered cardiopulmonary arrest (ventricular fibrillation: VF). After defibrillation in the ambulance, she was transported to our emergency department. Electrocardiography monitoring showed QT prolongation. Serum potassium level was extremely low at 1.8 mEq/l. Although potassium and lidocaine were administered, it was difficult to maintain appropriate electrolyte balance and prevent VF after admission, so temporary overdrive pacing was required. She was diagnosed as having primary aldosteronism after laboratory and imaging examinations. VF was otherwise uncontrollable so a cardioverter defibrillator was implanted on the 24th hospital day. Laparoscopic adrenalglandectomy was performed about 1 month later. After the surgery, serum potassium level remained at an appropriate level without medication. No severe neurological deficits were found at discharge from our hospital.

A 76-year-old woman was admitted to our hospital because of exertional dyspnea and leg edema during the previous month. Her systolic blood pressure on admission was 80 mmHg with 12 mmHg of pulsus paradoxous, and her pulse rate was 110 beats/min. Chest radiography revealed marked cardiomegaly and echocardiography showed massive pericardial effusion mainly behind the left ventricle and collapse of the right ventricle. The initial diagnosis was pericardial tamponade. Pericardiocentesis and pericardial drainage revealed bloody pericardial effusion. After drainage, her vital signs improved and her symptoms immediately disappeared. The cytological analysis of the pericardial effusion revealed numerous lymphoma cells. Computed tomography of the neck, chest and abdomen showed no evidence of tumor masses, lymph node enlargement, or hepatosplenomegaly. Infectious disease, collagen disease and aortic dissection were excluded. The final diagnosis was primary effusion lymphoma. The prognosis of primary effusion lymphoma is generally unfavorable because it is frequently accompanied by immunodeficiency disease. However, there was no human immunodeficiency virus infection in this patient. Fortunately, the effect of chemotherapy was excellent and the patient is doing well 1 year after the diagnosis.

A 59-year-old woman was admitted to our hospital because of exertional dyspnea, abdominal distension, and leg edema over the past 2 weeks. She had a history of rheumatic fever at the age of 12 years. In 1983, at the age of 37, she had undergone tricuspid valve replacement with a Carpentier-Edwards bioprosthesis for tricuspid stenosis and mitral valve replacement with a mechanical valve for mitral stenosis. The physical examination on admission revealed marked edema in both legs. There was also presystolic pulsation of the liver, which was palpable 4 cm below the right costal margin. A Levine grade III/VI, rough, diastolic rumble at the lower left sternal border was accentuated during inspiration. Echocardiography revealed severe tricuspid stenosis and a large amount of ascites. The leaflets were thickened, …

A 65-year-old woman presented with exertional dyspnea and general fatigue that began 1 week ago. She had a family history of hereditary hemorrhagic telangiectasia manifesting as telangiectasia of gastrointestinal (GI) tract and nasal mucosa and of pulmonary arteriovenous fistulas (PAVFs). Her first PAVF was diagnosed in 1999 but was untreated at that time. Her medical history was significant for multiple GI bleeds, mild to moderate nosebleeds, and a minor cerebral stroke probably due …

Aortic valve stenosis (AS) occurs with increased frequency in hemodialysis (HD) patients and could contribute to the excess cardiovascular mortality. However, little is known about differences in progression of the AS process between HD and non-HD patients. Neopterin, a by-product of the guanosine

It has been reported that idiopathic focal ventricular arrhythmias can originate from the papillary muscles in the left ventricle (LV), but the clinical features remains unclear and the treatment has not been established. We report on a 75-year-old male patient presenting with a dilated cardiomyopathy and frequent ventricular premature complexes (VPCs). Ventricular arrhythmia was refractory to betaxolol (10 mg), mexiletine (300 mg) and Atenolol (25 mg). Three years after the onset of palpitations the patient evolved from NYHA functional class I (NYHAI) to class III, with a LVEF of 28%. VPCs comprised 66% of the total number of QRS complexes during 24 h Holter monitoring (Holter). During electrophysiologic study LV geometry was reconstructed using a CARTO system and the activation maps for two types of frequent VPCs revealed centrifugal activation patterns from two separate sites at the anterior and posterior papillary muscle. Radiofrequency catheter ablation was performed, but could not eliminate VPCs. Then, Carvedilol, at a dose of 20 mg/day, was administrated and suppressed VPCs very effectively. One year later, the patient was in NYHAI with LV reverse remodeling and LVEF of 51%. Holter showed only 727 VPCs. In conclusion, frequent VPCs arising from the bilateral left papillary muscle induced significant LV dysfunction and it was supressed effectively with Carvedilol, following LV reverse remodeling.

Alpha glucosidase inhibitor (GI) attenuates postprandial hyperglycemia (PPH) and reduces the risk of cardiovascular events in patients with impaired glucose tolerance or type 2 diabetes. Dipeptidyl peptidase 4 (DPP-4) inhibitors also attenuate PPH. PPH is one of the factors leading to endothelial dysfunction which is an early event in the pathogenesis of atherosclerosis. Furthermore, DPP-4 inhibitors protect endothelial function through a GLP-1-dependent mechanism. However, the impact of these two types of drugs on endothelial dysfunction in patients with type 2 diabetes has not been fully elucidated. We compared the effects of sitagliptin, a DPP-4 inhibitor, and voglibose, an alpha GI, on endothelial function in patients with diabetes. We conducted a randomized prospective multicenter study in 66 patients with type 2 diabetes who did not achieve the treatment goal with sulfonylurea, metformin or pioglitazone treatment; 31 patients received sitagliptin treatment and 35 patients, voglibose treatment. The flow-mediated dilatation (FMD) of the brachial artery was measured in the fasting state at baseline and after 12 weeks of treatment. The primary endpoint was a change in FMD (ΔFMD) from the baseline to the end of follow-up. The effects of sitagliptin and voglibose on FMD were assessed by ANCOVA after adjustment for the baseline FMD, age, sex, current smoking, diabetes duration and body mass index. Secondary efficacy measures included changes in HbA1c, GIP, GLP-1, C-peptide, CD34, lipid profile, oxidative stress markers, inflammatory markers and eGFR and any adverse events. ΔFMD was significantly improved after 12 weeks of treatment in both groups, and there was no significant difference in ΔFMD between the two groups. There were no significant differences in changes in HbA1c, GIP, GLP-1, C-peptide, lipid profile, oxidative stress marker, inflammatory marker and eGFR between the two groups. Compared with voglibose, sitagliptin significantly increased the circulating CD34, a marker of endothelial progenitor cells. Adverse events were observed in 5 patients in only the voglibose group (diarrhea 1, nausea 1, edema 2 and abdominal fullness 1). Sitagliptin improved endothelial dysfunction just as well as voglibose in patients with type 2 diabetes. Sitagliptin had protective effects on endothelial function without adverse events. registered at http://www.umin.ac.jp/ctrj/ under UMIN000003951