Effect of Smoking Status on Monocyte Tissue Factor Activity, Carotid Atherosclerosis and Long-Term Prognosis in Metabolic Syndrome.

BACKGROUND: Smoking increases the risk of atherothrombotic events. Tissue factor (TF) mainly expressed on monocytes plays an important role in thrombosis and atherosclerosis. Metabolic syndrome (MetS) is being increasingly recognized as a major atherothrombotic risk factor, but the effects of smoking on monocyte TF activity (MTFA), carotid atherosclerosis estimated on carotid intima-media thickness (CIMT), and long-term prognosis in MetS remain unclear.Methods and Results:A total of 301 MetS patients lacking any known cardiovascular disease were prospectively investigated and classified into 4 groups according to smoking status at entry and at 12 months as follows: never smokers, past smokers, quitters, and persistent smokers. Peripheral blood mononuclear cells (PBMC) were isolated, and MTFA was measured using a coagulation assay. Linear trends for higher baseline MTFA and CIMT were observed among persistent smokers, quitters, and past smokers compared with never smokers. At 12 months, MTFA and CIMT decreased in never and past smokers and quitters but increased in persistent smokers. Six acute myocardial infarctions and 8 strokes occurred during a median follow-up of 66.0 months. Persistent smoking was associated with an increased risk of events (P<0.001). CONCLUSIONS: Smoking is associated with upregulated MTFA and progression of CIMT, which may be related to the risk of atherothrombotic events in MetS patients.

Serum Tartrate-resistant Acid Phosphatase-5b Levels are Associated with the Severity and Extent of Coronary Atherosclerosis in Patients with Coronary Artery Disease.

AIMS: Tartrate-resistant acid phosphatase (TRACP)-5b and osteoprotegerin (OPG) are specific and sensitive markers of bone resorption in patients with rheumatoid arthritis (RA) and chronic kidney disease (CKD). The TRACP-5b level is associated with the severity of RA and CKD, while the OPG level is associated with the severity of coronary atherosclerosis and calcification, and can predict a poor outcome in patients with coronary artery disease (CAD). However, the impact of TRACP-5b on coronary atherosclerosis in CAD patients remains unclear. METHODS: A total of 71 CAD patients (57 men, 14 women; mean age: 69.0±9.7 years) and 28 age- and gender- matched healthy subjects were investigated. The number of diseased vessels (a marker of the severity of coronary atherosclerosis) and the Gensini score (a marker of the extent of coronary atherosclerosis), as well as the OPG and TRACP-5b levels were measured in CAD patients. The TRACP-5b levels were classified into quartiles. RESULTS: The TRACP-5b levels were significantly higher in CAD patients than in healthy subjects. Patients with higher TRACP-5b levels had higher OPG levels and Gensini scores than those with lower TRACP-5b levels. Higher TRACP-5b levels were associated with an increased number of diseased vessels. A multivariate linear regression analysis showed that the OPG level and the number of diseased vessels or the Gensini score were significantly and independently associated with the TRACP-5b level. CONCLUSIONS: These data indicate that the TRACP-5b level is significantly associated with the OPG level and with the severity and extent of coronary atherosclerosis in CAD patients.

Nutritional Status is Associated with Inflammation and Predicts a Poor Outcome in Patients with Chronic Heart Failure.

AIM: Malnutrition has been identified to be an independent predictor of morbidity and mortality in patients with chronic heart failure (CHF). However, the pathophysiological mechanisms underlying this pathway remain unclear. METHODS: Nutritional screening was performed using the controlling nutritional status (CONUT) score, which was calculated using the serum albumin and total cholesterol levels and lymphocyte number, in 114 CHF patients with a mean left ventricular ejection fraction of 26.6%±6.4%. The carotid intima-media thickness (CIMT) is correlated with carotid atherosclerosis and is a significant predictor of future cardiovascular events. Peripheral blood mononuclear cells (PBMCs) were isolated, and the production of monocyte tumor necrosis factor (TNF)-α was measured and expressed as mean±SD (pg/mL/10(6) PBMCs). RESULTS: A multivariate linear regression analysis showed that the production of monocyte TNF-α (ß coefficient=0.434, p＜0.001) and mean CIMT (ß coefficient=0.204, p=0.006) were independent determinants of the CONUT score. During a median follow-up of 67.5 months, 45 patients experienced cardiac events, including 16 cardiac deaths and 29 readmissions for worsening CHF. A multivariate Cox hazard analysis demonstrated that a monocyte TNF-α level of ≥4.1 pg/mL/10(6) PBMCs (hazard ratio (HR), 14.10; 95% confidence interval (CI), 2.55-77.92; p=0.002) and CONUT score of ≥3 (HR, 11.97; 95% CI, 2.21-64.67; p=0.004) were independently associated with the incidence of cardiac events. CONCLUSIONS: These data indicate that a poor nutritional status as assessed using the CONUT score and atherosclerosis as indicated by CIMT is significantly associated with inflammation and predicts poor outcomes in patients with CHF.

Osteoprotegerin is Associated With Endothelial Function and Predicts Early Carotid Atherosclerosis in Patients With Coronary Artery Disease.

Osteoprotegerin (OPG) is a soluble glycoprotein belonging to the tumor necrosis factor receptor superfamily and is linked to vascular atherosclerosis and calcification. The carotid intima-media thickness (CIMT) correlates with carotid atherosclerosis and is a significant predictor of cardiovascular events. The OPG levels are associated with the CIMT in coronary artery disease (CAD) patients. However, the pathophysiological mechanisms underlying this pathway remain unclear. We investigated 114 CAD patients (89 men, 25 women; mean age: 68.7 ± 10.3 years) and measured the Gensini score (a marker of the extent of coronary atherosclerosis), the mean CIMT and the plasma levels of OPG and asymmetric dimethylarginine (ADMA; a marker of endothelial function). Early carotid atherosclerosis was defined as a mean CIMT > 1.0 mm. Only 33 of the 114 patients (28.9%) had early carotid atherosclerosis. Patients with early carotid atherosclerosis had higher OPG levels than those without. The OPG levels were found to be significantly associated with ADMA (r = 0.191, P = 0.046) and the mean CIMT (r = 0.319, P = 0.001), but not with the Gensini score. A receiver operating curve analysis revealed the optimal cut-off value of the OPG levels for predicting early carotid atherosclerosis to be 100 pmol/L. A multivariate logistic regression analysis showed OPG ≥ 100 pmol/L to be significantly and independently associated with early carotid atherosclerosis (odds ratio: 2.98, 95% confidence interval: 1.22-7.20, P = 0.017). These data indicate that OPG is significantly associated with endothelial function and predicts early carotid atherosclerosis in patients with CAD.

Differential Effects of Atorvastatin and Pitavastatin on Inflammation, Insulin Resistance, and the Carotid Intima-Media Thickness in Patients with Dyslipidemia.

AIMS: 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have multiple pleiotropic effects, such as anti-inflammatory and vascular endothelium protection, that are independent of their low-density-lipoprotein (LDL) cholesterol lowering effects. However, whether different statins exert diverse effects on inflammation, insulin resistance, and the progression of carotid atherosclerosis [as indicated by the intima-media thickness (CIMT)] in patients with dyslipidemia remains unclear. METHODS: A total of 146 patients with hypercholesterolemia without known cardiovascular disease were randomly assigned to receive 5 mg/day of atorvastatin (n=73) or 1 mg/day of pitavastatin (n=73). RESULTS: At baseline, age, gender, blood pressure, lipid profiles, and the serum monocyte chemoattractant protein (MCP)-1, homeostasis model assessment of insulin resistance (HOMA-IR) and CIMT values were comparable between the groups. After 12 months of treatment, atorvastatin and pitavastatin equally reduced the LDL cholesterol levels; however, atorvastatin increased the HOMA-IR by ＋26% and pitavastatin decreased this parameter by －13% (p＜0.001). The MCP-1 values were reduced by －28% in the patients treated with pitavastatin and only －11% in those treated with atorvastatin (p=0.016). A greater percent decrease in the mean CIMT from baseline was observed in the patients treated with pitavastatin than in those treated with atorvastatin (－4.9% vs. －0.5%, p=0.020). CONCLUSIONS: These data indicate that, while these agents significantly and equally reduce the LDL cholesterol levels, atorvastatin and pitavastatin have different effects on inflammation, insulin resistance, and the progression of carotid atherosclerosis in patients with dyslipidemia.

Relationships between the serum cholesterol levels, production of monocyte proinflammatory cytokines and long-term prognosis in patients with chronic heart failure.

OBJECTIVE: Low serum cholesterol is associated with a poor prognosis in patients with chronic heart failure (CHF). However, the relationships between the serum cholesterol level, production of monocyte proinflammatory cytokines and long-term prognosis in CHF patients remain unclear. METHODS: A total of 95 CHF patients who had not been treated with statins and had a mean left ventricular ejection fraction of 26.0±6.0% were examined. Peripheral blood mononuclear cells (PBMCs) were isolated, and the production of monocyte tumor necrosis factor (TNF)-α and interleukin (IL)-6 was measured and expressed as the mean ± SD (pg/mL/10(6) PBMCs). RESULTS: The production of monocyte TNF-α and IL-6 was found to be significantly and negatively associated with the serum low-density lipoprotein (LDL)-cholesterol level (TNF-α: r=-0.515, p<0.001, IL-6: r=-0.419, p<0.001). During a median follow-up of 66.0 months, 49 patients developed cardiac events, including 21 cardiac deaths and 28 readmissions for worsening CHF. A multivariate Cox hazard analysis showed that a monocyte TNF-α level of ≥4.9 pg/mL/10(6) PBMCs [hazard ratio (HR) 187.38, 95% confidence interval (CI) 7.92-4,434.94, p=0.001] and LDL-cholesterol level of <120 mg/dL (HR 9.41, 95% CI 1.02-86.66, p=0.048) were independently associated with the incidence of cardiac events. CONCLUSION: Low LDL-cholesterol and the upregulation of monocyte proinflammatory cytokine production are both significantly and independently associated with poor outcomes in CHF patients.

Effects of eicosapentaenoic acid on the levels of inflammatory markers, cardiac function and long-term prognosis in chronic heart failure patients with dyslipidemia.

AIMS: The effects of eicosapentaenoic acid (EPA) on the levels of inflammatory markers, cardiac function and long-term prognosis in chronic heart failure (CHF) patients with dyslipidemia remain unclear. METHODS: A total of 139 CHF patients with a mean left ventricular ejection fraction (LVEF) of 37.6± 8.0% were divided into two groups based on whether EPA was included in their treatment regimen: the EPA group (n=71) and the no EPA group (n=68). Only patients with dyslipidemia at baseline (entry) were treated with EPA. The monocyte chemoattractant protein (MCP)-1 and asymmetric dimethylarginine (ADMA) levels were measured at baseline and after 12 months of treatment. RESULTS: At 12 months, in the EPA group, the LVEF had improved and the MCP-1 and ADMA levels had decreased (respectively, p＜0.001); however, in the no EPA group, the LVEF had worsened, while the MCP-1 and ADMA levels had increased (respectively, p＜0.001). Fifty-five patients experienced cardiac events, including 15 cardiac deaths and 40 readmissions for worsening of CHF during a median follow-up period of 28.0 months. The percent change in LVEF from baseline was found to be significantly associated with the percent change in ADMA (r=-0.462, p＜0.001). A multivariate Cox hazard analysis showed EPA treatment (hazard ratio: 0.21, 95% confidence interval: 0.05-0.93, p=0.031) to be an independent predictor of cardiac events. CONCLUSIONS: These data indicate that EPA treatment may improve the cardiac function and long-term prognosis of CHF patients with dyslipidemia, at least in part, due to reductions in inflammation and improvements in the endothelial function.

Relationship between left ventricular dyssynchrony and systolic dysfunction is independent of impaired left ventricular myocardial perfusion in heart failure: assessment with 99mTc-sestamibi gated myocardial scintigraphy.

BACKGROUNDS: Left ventricular (LV) dyssynchrony reduces LV systolic function in patients with heart failure (HF). However, it remains unknown whether this relationship is independent of impaired LV myocardial perfusion. METHODS AND RESULTS: A total of 105 patients with chronic HF (age 71 ± 13 years; 71 men) were enrolled in the present study. (99m)Tc-sestamibi (MIBI) gated myocardial scintigraphy was performed at rest to assess LV myocardial perfusion as evaluated by the total defect score of perfusion Single Photon Emission Computed Tomography images (TDS-MIBI), LV systolic function as evaluated by LV ejection fraction (LVEF), and LV systolic dyssynchrony as evaluated by the maximal difference of time to end systole (MD-TES), which is the time lag between the earliest and the latest end systole among 17 LV segments analyzed with a novel program, "cardioGRAF". The mean ± SD (minimum and maximum range) of the MD-TES was 147.8 ± 117.5 (14.0-458.3)ms. The MD-TES was significantly higher in patients with LVEF<45% (199.4 ± 117.6 ms) than in those with LVEF ≥ 45% (60.5 ± 41.2 ms, p<0.001). In a multiple logistic regression analysis, the MD-TES showed an increased odds ratio for LVEF<45% (2.46 [95% CI; 1.51-4.01] per increment in decile of MD-TES rank, p<0.001), after adjusting for the TDS-MIBI, history of myocardial infarction, and other potential confounders. CONCLUSIONS: LV dyssynchrony is a significant determinant of LV systolic dysfunction in patients with HF, and this relationship is independent of impaired LV myocardial perfusion and history of myocardial infarction.

Effect of insulin resistance associated with compensatory hyperinsulinemia on the long-term prognosis in patients with vasospastic angina.

BACKGROUND: Insulin resistance associated with compensatory hyperinsulinemia plays a significant role in the pathogenesis of cardiovascular diseases, including vasospastic angina (VSA). However, the effects of insulin resistance associated with hyperinsulinemia on the long-term prognosis in patients with VSA remain unclear. METHODS: A total of 265 selected patients with VSA and 56 control subjects with atypical chest pain were enrolled in the present study. Patients with VSA had a positive acetylcholine (ACh) provocation test with normal coronary angiograms, and control subjects had a negative ACh test and normal coronary angiograms. A 75-g oral glucose tolerance test was performed, and the plasma glucose and immunoreactive insulin (IRI) levels were measured before, and 30 min and 120 min (IRI 120) after the 75-g glucose load. RESULTS: During the median follow-up period of 90.0 months, thirty-one patients developed cardiac events, including 6 sudden cardiac deaths and 25 readmissions for acute coronary syndrome. Cardiac events occurred in 38.9% of the patients with an IRI 120 ≥ 80 µU/ml and only 1.6% of the patients with an IRI 120<80 µU/ml (log rank 77.220, p<0.001). A multivariate analysis showed that an IRI 120 ≥ 80 µU/ml (hazard ratio 27.49, 95% confidence interval: 4.66-162.10, p<0.001) was an independent predictor of cardiac events. CONCLUSIONS: These data indicate that insulin resistance associated with compensatory hyperinsulinemia increases the risk of cardiac events in VSA patients.

Effects of statin therapy on the production of monocyte pro-inflammatory cytokines, cardiac function, and long-term prognosis in chronic heart failure patients with dyslipidemia.

BACKGROUND: The effects of statin therapy on the production of monocyte pro-inflammatory cytokines, cardiac function and the long-term prognosis in chronic heart failure (CHF) patients with dyslipidemia remain unclear. METHODS AND RESULTS: A total of 146 CHF patients with a mean left ventricular ejection fraction (LVEF) of 26.9 ± 6.6% were divided into 2 groups based on whether or not statins were included in their treatment: a statin group (n=63) and a no statin group (n=83). Only patients with dyslipidemia were treated with statins. Peripheral blood mononuclear cells (PBMCs) were isolated, and the production of monocyte tumor necrosis factor (TNF)-α and interleukin (IL)-6 were measured at baseline and after 6 months of treatment, and the data expressed as mean ± SD (pg·ml(-1)·10(-6) PBMCs). The LVEF in the statin group improved, and the monocyte TNF-α and IL-6 production decreased (respectively, P<0.001), but the LVEF and cytokine production remained unchanged in the no statin group. Multivariate Cox hazard analysis showed that statin therapy (hazard ratio, 0.14; 95% confidence interval: 0.02-0.97, P=0.046) was an independent predictor of cardiac events. CONCLUSIONS: Statin therapy attenuates the production of monocyte pro-inflammatory cytokines, and ameliorates the cardiac function and may improve long-term prognosis in CHF patients with dyslipidemia.

Effect of long-term nitrate treatment on cardiac events in patients with vasospastic angina.

BACKGROUND: Nitrates have been widely used as anti-ischemic drugs in patients with vasospastic angina (VSA). However, the effect of long-term nitrate treatment on cardiac events in VSA patients remains unclear. METHODS AND RESULTS: Two-hundred and thirty-one patients with VSA who had not been receiving any antiischemic drugs, including calcium channel blockers (CCBs), nitrates, nicorandil, or any combination of these medications were prospectively enrolled in the present study. All patients had a positive acetylcholine provocation test with normal coronary angiograms, and they received CCBs after enrollment. They were divided into 2 groups based on whether nitrates were included in the treatment: a nitrate group (n=86) and a without nitrate group (n=145). The baseline clinical characteristics and frequency of anginal attacks within 48h before enrollment were similar between the 2 groups. With a median follow-up period of 70.5 months, 29 patients developed cardiac events, including 7 sudden cardiac deaths and 22 re-admissions for acute coronary syndrome. Cardiac events occurred in 19.8% of the nitrate group and in only 8.3% of the patients who were not taking nitrates (P=0.015). In a multivariate analysis, long-term nitrate treatment (hazard ratio 5.18, 95% confidence interval: 1.69-15.89, P=0.004) was an independent predictor of cardiac events. CONCLUSIONS: These data indicate that long-term nitrate treatment in addition to CCBs might not reduce cardiac events in VSA patients.

Secondary preventive effects of a calcium antagonist for ischemic heart attack: randomized parallel comparison with ß-blockers.

BACKGROUND: Beta-blockers (BB) have been widely used in the management of hypertension and acute myocardial infarction (AMI), and both national and international guidelines have recommended them as first-line agents. Calcium channel antagonists (CCA) are also effective in the treatment of hypertension and angina pectoris. However, the efficacy of CCA in the prevention of cardiovascular events in post-myocardial infarction (MI) patients in comparison to that of BB remains unclear. METHODS AND RESULTS: A total of 120 post-MI patients (71 patients who were at least 1 month after the onset AMI and 49 stable coronary artery disease patients with a history of MI) were randomly assigned to receive a BB (atenolol, 25-50mg/day, n=60) or a CCA (benidipine, 4-8 mg/day, n=60). All patients with AMI within the previous 1 month or with vasospastic angina were excluded from the present study. The baseline clinical characteristics were generally similar in the BB and CCA groups. The rate of primary composite outcome was 26.3% in the BB group in comparison to 13.3% in the CCA group, with no significant between-group differences (hazard ratio with the CCA group 0.640, P=0.276). Both treatments were well tolerated with few severe adverse events. CONCLUSIONS: CCA treatment was found to be as effective as BB in reducing cardiovascular events in post-MI patients.

Upregulation of monocyte tissue factor activity is significantly associated with carotid intima-media thickness in patients with metabolic syndrome.

AIMS: Metabolic syndrome (MS) represents a cluster of cardiovascular risk factors and an increased risk of cardiovascular events. The carotid intima-media thickness (CIMT) is correlated with coronary and carotid atherosclerosis, and is a significant predictor of cardiovascular events. Tissue factor (TF) is an initiator of the extrinsic coagulation cascade and is expressed on peripheral blood monocytes and macrophages in atherosclerotic plaques. TF plays important roles in both thrombosis and atherosclerosis. No study has investigated the relationship between monocyte TF activity and CIMT in MS patients. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from 39 normal subjects and 110 patients with MS. The procoagulant activity (PCA) in monocytes was measured using a one-stage clotting assay and is expressed as the mean±SD (mU TF/10(6) PBMCs). RESULTS: The PCA in monocytes in MS patients was significantly higher than in normal subjects (86.2 ±69.5 vs. 52.4±9.9 mU TF/10(6) PBMCs, p < 0.001). In multivariate analysis, patient age (ß coefficient= 0.373, p < 0.001), high-density lipoprotein cholesterol (ß coefficient=-0.307, p = 0.001) and PCA (ß coefficient= 0.422, p =0.002) were each significantly and independently associated with CIMT. CONCLUSIONS: These data indicate that the upregulation of monocyte TF activity is significantly associated with CIMT in MS patients.

Variant angina and coronary artery spasm: the clinical spectrum, pathophysiology, and management.

Variant angina is a form of angina pectoris that shows transient ST-segment elevation on electrocardiogram during an attack of chest pain. Ischemic episodes of variant angina show circadian variation and often occur at rest from midnight to early morning. Ischemic episodes also occur during mild exercise in the early morning. However, they are not usually induced by strenuous exercise in the afternoon. Other important clinical features of variant angina include the high frequency of asymptomatic ischemic episodes and the syncope that sometimes occur during the ischemic episodes. Syncope is due to severe arrhythmias, including ventricular tachycardia, ventricular fibrillation, and high-degree atrioventricular block. Coronary artery spasm is the mechanism of ischemic episodes in variant angina. The incidence of coronary artery spasm shows a racial difference and is higher in Japanese than in Caucasians. Coronary arteriograms are normal or near-normal in most Japanese patients with variant angina. Deficient basal release of nitric oxide (NO) due to endothelial dysfunction, and enhanced vascular smooth muscle contractility with the involvement of the Rho/Rho-kinase pathway are reported to play important roles in the pathogenesis of coronary artery spasm. Other precipitating factors of coronary artery spasm include imbalance in autonomic nervous activity, increased oxidative stress, chronic low-grade inflammation, magnesium deficiency, and genetic susceptibility. The genetic risk factors associated with coronary artery spasm include gene polymorphisms of endothelial NO synthase (NOS), paraoxonase, and other genes. Calcium channel blockers are extremely effective in preventing coronary spasm. The long-acting nitrate, nicorandil, and Rho-kinase inhibitor are also useful for inhibiting coronary artery spasm. Because variant angina can lead to acute myocardial infarction, fatal arrhythmias, and sudden death, early treatment is important. The prognosis of patients with variant angina is favorable, if early complications can be overcome. However, because coronary artery spasm cannot be suppressed in some patients, even with multiple medications, medications to suppress intractable coronary artery spasm must be developed.

Elevated peripheral blood mononuclear cell count is an independent predictor of left ventricular remodeling in patients with acute myocardial infarction.

OBJECTIVES: Peripheral blood mononuclear cells (PBMCs) increase after acute myocardial infarction (AMI) and infiltrate to the infarct region. However, its impact on left ventricular (LV) remodeling remains unclear. The purpose of the present study was to clarify whether elevated PBMC count contributed to LV remodeling in patients with AMI. SUBJECTS AND METHODS: A total of 131 patients with AMI were recruited. White blood cell (WBC), monocyte, and lymphocyte counts were measured at presentation and every 24h for five days after presentation. The correlation between PBMC count and LV remodeling was evaluated. LV remodeling was defined as an increase of LV end-diastolic volume index ≥ 10% at the 6-month follow-up left ventriculography. RESULTS: Forty-eight patients had LV remodeling. Peak WBC (p=0.008), peak monocyte (p=0.001), and peak PBMC (p<0.001) counts were significantly greater in patients with LV remodeling than those without remodeling. Multivariate analysis revealed the peak PBMC count ≥ 3600/mm(3) was an independent predictor of LV remodeling [relative risk (RR) 3.243, p=0.011]. CONCLUSION: Increased PBMC count is significantly correlated with LV remodeling, thus suggesting that PBMCs play a pivotal role for the development of LV remodeling after AMI.

Impact of statin therapy on renal function and long-term prognosis in acute coronary syndrome patients with chronic kidney disease.

A recent study showed that statins reduce cardiovascular events in stable coronary artery disease patients with chronic kidney disease (CKD). However, it remains unclear whether acute coronary syndrome (ACS) patients with CKD benefit from statins. A total of 501 patients with ACS who underwent successful percutaneous coronary intervention were investigated and CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/minute/1.73 m(2) at discharge. Three hundred and twenty-four of 501 patients (64.7%) had CKD and 173 patients (34.5%) received statins. The patients with CKD were older and had higher blood pressure than those without CKD. With a mean follow-up of 5.2 years, irrespective of treatment assignment, 74 patients with CKD experienced cardiac events (22.8%) in comparison to 25 without CKD (14.1%, HR 1.81; 95% CI 1.15-2.84, P = 0.0095). Cardiac events occurred in only 18 of the patients with CKD treated with statins (16.2%) and in 56 of those treated with CKD without statins (26.3%, HR 0.58; 95% CI 0.34-0.98, P = 0.039), whereas, no significant reduction of the events was observed in the patients without CKD treated with statins versus without having statins (P = 0.130). These data indicate that statin therapy reduces cardiac events in ACS patients with CKD.

Cardiac angiosarcoma diagnosed by transvenous endomyocardial biopsy with the aid of transesophageal echocardiography and intra-procedural consultation.

We report a case who had confirmed tumor cells in the biopsy specimens by transvenous endomyocardial biopsy with intra-procedural consultation and fast smear cytology. A 57-year-old female was admitted to our hospital because of shortness of breath and left back pain. Transthoracic echocardiography (TTE) and contrast-enhanced computed tomography (CT) scans demonstrated a large mass in the right atrium and multiple liver tumors thought to be due to spread of the disease. Coronary angiography showed the right coronary artery was involved in the mass. In order to confirm the histological diagnosis, we attempted transvenous endomyocardial tumor biopsy under fluoroscopic guidance. However, we failed to obtain adequate tissue material. Due to several risks associated with a surgical procedure such as an open surgical biopsy, transvenous endomyocardial tumor biopsy was again attempted with the aid of transesophageal echocardiography (TEE). Intra-procedural consultation and fast smear cytology enabled us to finish the procedure. Hematoxylin-eosin stained sections demonstrated spindle-shaped cells. Immunohistochemical stains of these cells were positive for anti-factor VIII antigen, CD31, and CD34. These findings indicated a definite diagnosis of angiosarcoma. Since there was no surgical indication for this tumor, the patient underwent chemotherapy with docetaxel and radiotherapy. Three months later, CT scans showed a reduction in the size of the cardiac tumor.