Comparison of Direct Oral Anticoagulants and Warfarin in the Treatment of Deep Venous Thrombosis in the Chronic Phase.

We assessed the efficacy and safety of direct oral anticoagulants (DOACs) for the treatment of deep venous thrombosis (DVT) in the chronic phase through comparison with conventional warfarin therapy.A total of 807 consecutive patients who were diagnosed with having DVT in the chronic phase were included (484 patients to warfarin therapy and 323 patients to DOAC therapy). The condition of leg veins was assessed 3 to 6 months after starting the therapies by ultrasound examination. Major bleeding and mortality during the therapies were followed-up.There was no significant difference between the two groups in the thrombosis improvement rate (DOAC group: 91.2% versus warfarin group: 88.9%). There was no significant difference between the two groups in major bleeding (DOAC group: 1.8% versus warfarin group: 1.8%). In patients with active cancer, the DOAC group had a borderline higher thrombosis improvement rate than the warfarin group (92.1% versus 80.0%, P = 0.05). The proportion of major bleeding in the patients with active cancer was slightly higher in the warfarin group than in the DOAC group (4.3% versus 2.8%; P = 0.71). Active cancer was not an independent risk factor for major bleeding and recurrence in the DOAC group (OR 2.68, 95% CI 0.51-14.1; P = 0.24 and OR 0.65, 95% CI 0.20-2.07; P = 0.47).In treatment using oral anticoagulants for DVT in the chronic phase, DOACs exhibited equal efficacy and safety as warfarin did. Particularly DOACs appear to be an attractive therapeutic option for cancer-associated DVT in chronic phase, with relatively low anticipated rates of recurrence and major bleeding.

Molecular Hydrogen Alleviates Cellular Senescence in Endothelial Cells.

BACKGROUND: Substantial evidence indicates that molecular hydrogen (H2) has beneficial vascular effects because of its antioxidant and/or anti-inflammatory effects. Thus, hydrogen-rich water may prove to be an effective anti-aging drink. This study examined the effects of H2on endothelial senescence and clarified the mechanisms involved. METHODS AND RESULTS: Hydrogen-rich medium was produced by a high-purity hydrogen gas generator. Human umbilical vein endothelial cells (HUVECs) were incubated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for various time periods in normal or hydrogen-rich medium. The baseline H2concentration in hydrogen-rich medium was 0.55±0.07 mmol/L. This concentration gradually decreased, and H2was almost undetectable in medium after 12 h. At 24 h after TCDD exposure, HUVECs treated with TCDD exhibited increased 8OHdG and acetyl-p53 expression, decreased nicotinamide adenine dinucleotide (NAD(+))/NADH ratio, impaired Sirt1 activity, and enhanced senescence-associated ß-galactosidase. However, HUVECs incubated in hydrogen-rich medium did not exhibit these TCDD-induced changes accompanying Nrf2 activation, which was observed even after H2was undetectable in the medium. Chrysin, an inhibitor of Nrf2, abolished the protective effects of H2on HUVECs. CONCLUSIONS: H2has long-lasting antioxidant and anti-aging effects on vascular endothelial cells through the Nrf2 pathway, even after transient exposure to H2. Hydrogen-rich water may thus be a functional drink that increases longevity. (Circ J 2016; 80: 2037-2046).

[Fibrates].

Although fibrates was a medicine with a long history, at the clinical spot, the profitability had not permeated as compared with statin. However, many-sided effects, such as a fall of a cardiovascular event and control of arteriosclerosis prevention and a diabetic microangiopathy, were reported as a result of the large-scale clinical test in recent years. Accumulation of the further clinical evidence of a fibrates is expected.

[Gastrointestinal hemorrhage associated with concurrent use of sorafenib and warfarin for hepatocellular carcinoma].

A 60-year-old man with liver cirrhosis caused by hepatitis C, who was receiving warfarin anticoagulation following acute myocardial infarction, was diagnosed with advanced hepatocellular carcinoma and multiple lung metastases, and began treatment with sorafenib 200 mg daily. From the treatment's start to 14 and 63 days later, sorafenib was increased to 400 mg and 600 mg, respectively. After increasing the quantity to 600 mg, he had an increase in PT-INR values and experienced a lower-extremity hemorrhage. For the patient with liver cirrhosis, who is receiving warfarin, PT-INR values might be elevated during the early period of sorafenib treatment dosage as for the increase in quantity. Therefore, when increasing dosage, a frequent measurement of PT-INR and a careful follow-up for PT-INR is necessary.

[A case of hereditary diffuse leukoencephalopathy with spheroids and pigmented glia presenting with long-term mild psychiatric symptoms].

A 64-year-old woman visited our hospital with early-onset dementia and progressive gait disturbance. She had demonstrated a mild communication disorder at the age of ~40 years; however, her psychiatric symptoms at that time were mild and were not accompanied by social problems. At the age of 59, she presented with memory loss, visual hallucinations, and delusions. Over the following five years she developed gait difficulties that gradually deteriorated and suffered frequent falls. On admission, neurological examinations revealed severe pyramidal and extrapyramidal signs of akinetic mutism. MRI of the brain showed cerebral atrophy, enlarged lateral ventricles, thinning of the corpus callosum, and leukoencephalopathy in the frontal-parietal lobes. Additionally, CT revealed a small spotty calcification in the frontal subcortical white matter. Genetic analysis revealed a single-base substitution (c.2330G>A/p.R777Q) in exon 18 of the colony stimulating factor 1 receptor (CSF1R) gene, encoding the CSF1R protein. She was diagnosed with hereditary diffuse leukoencephalopathy with spheroids (HDLS). HDLS is included in the differential diagnosis of early-onset dementia and should be considered in patients with mild personality change and abnormal behavior in the early course of the illness.

Outcome of pitavastatin versus atorvastatin therapy in patients with hypercholesterolemia at high risk for atherosclerotic cardiovascular disease.

BACKGROUND: There has been no report about outcome of pitavastatin versus atorvastatin therapy in high-risk patients with hypercholesterolemia. METHODS: Hypercholesterolemic patients with one or more risk factors for atherosclerotic diseases (n = 664, age = 65, male = 54%, diabetes = 76%, primary prevention = 74%) were randomized to receive pitavastatin 2 mg/day (n = 332) or atorvastatin 10 mg/day (n = 332). Follow-up period was 240 weeks. The primary end point was a composite of cardiovascular death, sudden death of unknown origin, nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack, or heart failure requiring hospitalization. The secondary end point was a composite of the primary end point plus clinically indicated coronary revascularization for stable angina. RESULTS: The mean low-density lipoprotein cholesterol (LDL-C) level at baseline was 149 mg/dL. The mean LDL-C levels at 1 year were 95 mg/dL in the pitavastatin group and 94 mg/dL in the atorvastatin group. There were no differences in LDL-C levels between both groups, however, pitavastatin significantly reduced the risk of the primary end point, compared to atorvastatin (pitavastatin = 2.9% and atorvastatin = 8.1%, HR, 0.366; 95% CI 0.170-0.787; P = 0.01 by multivariate Cox regression) as well as the risk of the secondary end point (pitavastatin = 4.5% and atorvastatin = 12.9%, HR = 0.350; 95%CI = 0.189-0.645, P = 0.001). The results for the primary and secondary end points were consistent across several prespecified subgroups. There were no differences in incidence of adverse events between the statins. CONCLUSION: Pitavastatin therapy compared with atorvastatin more may prevent cardiovascular events in hypercholesterolemic patients with one or more risk factors for atherosclerotic diseases despite similar effects on LDL-C levels.

Assessment of left ventricular diastolic function using color kinesis: differentiation between normal and pseudonormalized patterns.

PURPOSE: Doppler examination of transmitral flow has been widely used to noninvasively assess left ventricular (LV) diastolic function. However, it has been demonstrated that transmitral flow velocity is dependent on LV relaxation and left atrial pressure. Increases in left atrial pressure compensate for the effects of impaired LV relaxation, frequently resulting in a "pseudonormalization" of the transmitral flow pattern. The purpose of this study was to assess whether analysis of diastolic color kinesis (CK) can be applied to differentiation between normal and pseudonormalized (PN) patterns of LV inflow. METHODS: We studied 60 subjects with a ratio of early to late transmitral peak velocities (E/A) greater than 1.0 according to conventional Doppler echocardiography. All subjects simultaneously underwent measurement of the early diastolic mitral annular velocity (e'), which was measured by tissue Doppler imaging, and LV ejection fraction (EF), which was calculated by the modified Simpson method. Study subjects were classified into the following three groups according to the value of e' and EF: (1) the normal group (e' > 10 cm/s, EF > 60%), including 20 subjects (mean age 35 ± 10 years); (2) the PN1 group (e' < 7 cm/s, EF > 50%), consisting of 20 patients [mean age 63 ± 11 years, 15 patients with hypertensive heart disease (HHD), 5 patients with aortic valve stenosis]; and (3) the PN2 group (e' < 7 cm/s, EF < 50%), consisting of 20 patients (mean age 61 ± 17 years, 18 patients with dilated cardiomyopathy, 2 patients with HHD). Diastolic CK images were obtained for each subject from the LV midpapillary short-axis view. Analysis of CK diastolic images was performed using ICK software. The CK-diastolic index (CK-DI) was defined as the calculated LV segmental filling fraction during the first 30% of diastole, expressed as a percentage. The mean CK-DI was determined from the average CK-DI of six LV segments. RESULTS: The mean CK-DI was 70.9% ± 6.5% in the normal group, 46.3% ± 10.4% in the PN1 group, and 36.3% ± 5.1% in the PN2 group. The mean CK-DI was significantly reduced in the PN1 and PN2 groups compared with the normal group (P < 0.0001). Although there was no difference in e' (PN1 group: 4.6 ± 1.8 cm/s, PN2 group: 4.4 ± 1.7 cm/s) between the two pseudonormalized patient groups, the mean CK-DI was significantly reduced in the PN2 group compared with the PN1 group (P < 0.005). The reduction in mean CK-DI was seen not only in pseudonormalized patients with LV systolic dysfunction but also in those with preserved LV systolic function. CONCLUSION: The analysis of diastolic CK with ICK software is a useful method for detecting delayed early diastolic relaxation. We concluded that diastolic CK images may be applied to differentiating between normal and pseudonormalized patterns of LV inflow.

Correlation between plasma brain natriuretic peptide levels and left atrial appendage flow velocity in patients with non-valvular atrial fibrillation and normal left ventricular systolic function.

BACKGROUND: The left atrial appendage (LAA) flow velocity is an important factor for thrombus formation in patients with non-valvular atrial fibrillation (NV-AF). Recently, the relation of plasma brain natriuretic peptide (BNP) levels and thromboembolism has been reported in patients with NV-AF. The aim of this study was to determine whether the plasma BNP is predictive of lower LAA flow velocity in patients with NV-AF and normal left ventricular (LV) systolic function. METHODS AND RESULTS: A total of 184 patients with NV-AF (132 men; 65 ± 12 years, LV ejection fraction; 65 ± 10%) underwent transthoracic echocardiography, transesophageal echocardiography (TEE), and measurement of plasma BNP. The LAA flow velocity was obtained by pulsed Doppler TEE. Multivariate logistic regression analysis demonstrated that plasma BNP levels, left atrial volume index (LAVI), LV mass index (LVMI), and the CHADS2 score were independent predictors of lower LAA flow velocity (< 20 cm/s). Plasma BNP levels (r = - 0.58, p < 0.001) were correlated with LAA flow velocity. The area under the curve (AUC) for BNP (AUC 0.803) was larger than that for the CHADS2 score (AUC 0.712), LAVI (AUC 0.664) and LVMI (AUC 0.608) with an optimal BNP cut-off value of 164 pg/ml (sensitivity 75.7%, specificity 71.1%). CONCLUSIONS: This study showed that a higher plasma BNP was associated with a lower LAA flow velocity in patients with NV-AF and normal LV systolic function. The plasma BNP may complement the role of the CHADS2 score in predicting lower LAA flow velocity.

Reactive oxygen species depolymerize hyaluronan: involvement of the hydroxyl radical.

We have previously demonstrated that reactive oxygen species (ROS) are involved in cartilage degradation. A decrease in the size of hyaluronan (HA), which is the major macromolecule in synovial fluid and is responsible for imparting viscosity to it, is reported in arthritis patients. The purpose of this study is to determine the ROS that depolymerize HA. The luminol derivative, L-012, was used to determine the generation of ROS. To generate hydroxyl radicals, a mixture of hydrogen peroxide (H(2)O(2)) and ferrous ions (Fe(2+)) was added to HA. The antioxidants and the depolymerization of HA were studied in this system. The hydroxyl radical is one of the ROS, causing the depolymerization of HA, which reacts with L-01. These data suggest that hydroxyl radicals play an important role at the site of inflammation.

Transcatheter atrial septal defect closure in a patient with paradoxical brain emboli: who should treat it and who should be treated?

This report presents the case of a 51-year-old female who was admitted to a local hospital because of a persistent headache. A diagnosis of multiple cerebral infarctions was thereafter made, but there was no evidence of either atherosclerosis or atrial fibrillation. The case was thought to be a cryptogenic stroke, however, Doppler ultrasonography of the lower extremities showed venous insufficiency. Transesophageal echocardiography revealed a secundum atrial septal defect (ASD) with a left to right shunt. Therefore, the final diagnosis was paradoxical brain emboli, and transcatheter ASD closure was successfully performed by cardiologists without any sequelae.

Spontaneous superficial temporal artery pseudoaneurysm in elderly women--three case reports.

Three women older than 75 years presented with spontaneous superficial temporal artery (STA) pseudoaneurysms manifesting as a pulsatile mass in the preauricular region. None of the patients had a history of trauma. Histological examination of the surgically removed masses identified pseudoaneurysms based on the presence of connective tissue and adventitia. Spontaneous STA pseudoaneurysms are extremely rare. We suggest that all 3 aneurysms were associated with latent dissection and external force exerted by the frames of glasses.

Correlation between plasma B-type natriuretic peptide levels and left ventricular diastolic function using color kinetic imaging.

BACKGROUND: B-type natriuretic peptide (BNP) has been used widely as an objective marker for severity and prognostic predictor of heart failure. Recently it has been reported that plasma BNP level is associated with left ventricular (LV) diastolic dysfunction. Color kinesis (CK), a technique based on acoustic quantification, has been developed to facilitate the evaluation of regional wall motion and LV function. The aim of this study is to investigate the relationship between plasma BNP levels and LV diastolic function using diastolic CK imaging. METHODS AND RESULTS: The study included 65 subjects in sinus rhythm who were referred for echocardiography to evaluate cardiac function with simultaneous measurements of plasma BNP. Thirty-five patients were in New York Heart Association class I or II, and 15 were in class III or IV. We performed echocardiography with assessment of LV function, including LV ejection fraction (EF), transmitral flow (E/A), early diastolic mitral annular velocity (e'), and diastolic CK. Diastolic CK images, obtained from LV mid-papillary short-axis view, were analyzed using ICK software. The CK-diastolic index (CK-DI) was defined as the calculated LV segmental filling fraction during the first 30% of diastole, expressed as a percentage. The mean CK-DI was determined from the average CK-DI of six segments (anterior, anteroseptal, septal, inferior, posterior, lateral wall). Blood for BNP was collected on the same day as the echocardiographic study. We found significant correlations between mean CK-DI and log BNP (r=-0.66, p<0.0001), whereas log BNP correlated weakly with EF (r=-0.26), E/A (r=0.22), DT (r=-0.15) and E/e' (r=0.41). CONCLUSION: Our results suggest that the plasma BNP level may be related to LV relaxation. The analysis of diastolic CK may be useful for quantitative assessment of LV diastolic function in patients with heart failure.