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Yasushi Kono,1 Shota Fukuda,1 Kenei Shimada,2 Koki Nakanishi,2 Kenichiro Otsuka,2 Tomoichiro Kubo,1 Satoshi Jissho,1 Haruyuki Taguchi,1 Junichi Yoshikawa,3 Minoru Yoshiyama21Department of Medicine, Osaka Ekisaikai Hospital, Nishi-ku, Osaka, Japan; 2Department of Internal Medicine and Cardiology, Osaka City University School of Medicine, Abeno-ku, Osaka, Japan; 3Nishinomiya Watanabe Cardiovascular Center, Nishinomiya, JapanBackground: It has been reported that pitavastatin improves endothelial function faster than other statins. Recently introduced reactive hyperemia peripheral arterial tonometry (RH-PAT) provides objective and quantitative assessment of peripheral microvascular function.Purpose: This study aimed to investigate whether peripheral microvascular function improved 2 hours after pitavastatin in subjects with coronary artery disease (CAD) using RH-PAT, and the results were compared with those of rosuvastatin.Methods: This study included 94 subjects with CAD, assigned to a group given 2 mg of pitavastatin (n = 36), a group given 2.5 mg of rosuvastatin (n = 38), and a control group (n = 20). RH-PAT examinations were performed before and 2 hours after statin administration.Results: The RH-PAT index increased 2 hours after pitavastatin administration from 1.82 ± 0.45 to 2.16 ± 0.62 (P = 0.02), whereas there were no differences in the RH-PAT index in the rosuvastatin group (1.79 ± 0.71 to 1.91 ± 0.53, P = 0.09) and the control group (1.68 ± 0.36 to 1.84 ± 0.58, P = 0.4). No significant changes were observed at 2 hours in serum cholesterol levels in each group.Conclusion: The present study demonstrated that peripheral microvascular function improved 2 hours after a single clinical dose of pitavastatin, but not after rosuvastatin.Keywords: coronary artery disease, statin, microvascular function

Objective. Epicardial adipose tissue (EAT) is recognized as a novel risk factor for coronary artery disease (CAD), and its contribution is thought to be stronger in non-obese patients than in obese patients. However, the prognostic impact of the progression of EAT accumulation after comprehensive management for atherosclerotic risk factors remains unclear. This study aimed to investigate whether an increase of the EAT volume during follow-up predicts future acute coronary syndrome (ACS) events in non-obese CAD patients. Methods. This study consisted of 517 non-obese CAD patients (368 men; age, 66 ± 10 years) who underwent serial multidetector computed tomography (MDCT) examinations to evaluate coronary atherosclerosis progression. The MDCT examination was used to assess the severity of stenosis, plaque characteristics, and EAT volume. All patients received comprehensive management to reduce CAD risk factors after the first MDCT examination. The MDCT examination was repeated at 6-24 months, and patients were followed-up for more than 1 year or until the occurrence of ACS events. Results. Of 517 patients, 159 (31%) patients were classified into increase of EAT volume during follow-up, 91 (18%) into decrease of EAT volume during follow-up, and 267 (51%) patients into constant of EAT volume during follow-up. The prevalence of obstructive plaques and MDCT-derived vulnerable features of coronary plaques were significantly elevated in patients with increase of EAT volume during follow-up. In contrast, no significant changes were observed in the other 2 groups. During the follow-up period of 4.1 ± 1.8 years (median 4.4 years) after the second MDCT examination, ACS occurred in 43 (8.3%) patients. Multivariate Cox regression analysis showed that the presence of low-attenuation plaque (hazard ratio [HR]; 1.78, p = 0.04) and napkin-ring sign (HR; 3.74, p < 0.001) at second MDCT examination, and changes of EAT volume per 10 ml (HR; 1.34, p = 0.004) were associated with future ACS events. Conclusion. Patients with increase of EAT volume during follow-up despite comprehensive management for CAD risks had an increased prevalence of obstructive plaques and plaques with high-risk features, which could be associated with unfavorable ACS outcomes in non-obese CAD patients., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

We described a 19 year old female case with renovascular hypertension, whose blood pressure was high taking antihypertensive medications. The right renal artery was completely occluded at its ostium, and percutaneous transluminal renal angioplasty was unsuccessful. After aortorenal bypass surgery, blood pressure was normalized without administration of antihypertensive medication.

Background: The circadian change in coronary microvascular function has not been directly assessed in human beings. Recent advances in transthoracic Doppler echocardiography (TTDE) provide noninvasive, physiological assessment of coronary flow velocity reserve (CFVR)., Methods: This study consisted of 20 young healthy subjects (24 ± 2 years, 20 men) who underwent CFVR examinations at 3 different times; early morning (6AM), late morning (11AM) and late evening (10PM). The flow velocity in the distal portion of the left anterior descending coronary artery was measured with TTDE at baseline and during adenosine infusion to calculate CFVR. These examinations were repeated with the intake of α1-blocker (prazosin 1mg) on the other day., Results: CFVR showed a circadian variation with an increase from the early morning to the late morning, following a decrease to the late evening thereafter (4.4 ± 0.9 at 6AM; 5.2 ± 1.3 at 11AM; 4.2 ± 1.1 at 10PM, p<0.001). In the study with α1-blocker, CFVR was comparable between the early morning and the late morning, whereas CFVR in the late evening was lower than those in other 2 time points (5.0 ± 1.1 at 6AM; 4.9 ± 0.9 at 11AM; 4.3 ± 0.9 at 10PM, p<0.001)., Conclusions: This study demonstrates that CFVR has a circadian variation in humans, with an increase from the late evening to the late morning. Adding α1-blocker ameliorated CFVR only in the early morning, indicating that α1-sympathetic activity plays a heterogeneous and important role in the circadian change of CFVR in humans., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Anticoagulation therapy reduces the risk of thromboembolic events by two-thirds in patients with atrial fibrillation (AF). The prevalence of left atrial thrombus (LAT) in AF patients with anticoagulation therapy has not been fully investigated., Purpose: To investigate the prevalence of LAT and its impact on the outcomes in patients with nonvalvular AF after anticoagulation therapy., Methods: This study consisted of 231 patients with nonvalvular AF who had transthoracic (TTE) and transesophageal echocardiographic (TEE) examinations more than 3 weeks after anticoagulation therapy. The clinical and echocardiographic characteristics were evaluated., Results: LAT was observed in 13 (8.8%) of 148 patients with sub-therapeutic anticoagulation, and in 3 (3.6%) of 83 patients with sufficient anticoagulation. The presence of LAT was associated with higher CHADS(2) score, decreased LA volume changes and the presence of spontaneous echocardiographic contrast (SEC) in patients with sub-therapeutic anticoagulation. Patients with LAT after sufficient anticoagulation were male with permanent AF who had decreased left ventricular systolic and diastolic function and dilated LA on TTE and SEC, and reduced appendage flow velocity on TEE. Patients with LAT had worse cardiovascular outcomes compared with those without LAT (p=0.02)., Conclusions: We demonstrated that LAT was a univariate risk factor associated with worse cardiovascular outcomes, which was observed in 8.8% of patients with sub-therapeutic anticoagulation and 3.6% of patients with sufficient anticoagulation., (Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Night-shift work causes mental stress and lifestyle changes, and is recognized as a risk of cardiovascular diseases associated with impaired endothelial function. Aromatherapy is becoming popular as a complementary therapy that is beneficial for mental relaxation. The purpose of this study was to investigate the effect of aromatherapy on the endothelial function of medical staff after night-shift work. This study consisted of 19 healthy medical personnel (19 men, mean age 32 ± 7 years), including 11 physicians and 8 technicians. Aromatherapy was performed for 30 min by inhalation of the essential oil of lavender. Flow-mediated dilation (FMD) of the brachial artery was measured three times in each subject: on a regular workday, and after night-shift work before and immediately after aromatherapy. A control study was performed to assess the effect of a 30-min rest without aromatherapy. The mean value of sleep time during night-shift work was 3.3 ± 1.3 h. FMD after night-shift work was lower than on a regular workday (10.4 ± 1.8 vs. 12.5 ± 1.7%, P<0.001), which improved after aromatherapy (11.8 ± 2.5%, P=0.02 vs. before aromatherapy). FMD was stable in the control study (10.1 ± 1.9 vs. 10.1 ± 2.2%, P=0.9). This study demonstrated that night-shift work impaired endothelial function in medical staff, an effect that was alleviated by short-term aromatherapy.

Background: Electrocardiographic (ECG) left ventricular hypertrophy (LVH) is a risk factor for cardiovascular events and the incidence of LVH increases with age. However, few studies have assessed risks associated with LVH in elderly hypertensive patients., Methods and Results: The Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients (JATOS) was conducted to determine optimal blood pressure in elderly patients. At study entry, the sum of the S-wave in lead V(1) and the R-wave in lead V(5) (SV1+ RV5) could be determined in 3,230 patients, among whom 164 (5.1%) had cardiovascular events. On univariate analysis, the hazard ratio for cardiovascular events was 1.51 for each 10 mm (=1 mV) (95% confidence interval (CI): 1.34-1.69, P<0.0001) when SV1+ RV5 was considered a continuous variable, and 2.17 (95%CI: 1.54-3.05, P<0.0001) and 2.83 (95%CI: 1.91-4.19, P<0.0001) when SV1+ RV5 was classified into 2 groups at threshold values of either 35 mm or 40 mm, respectively. Multivariate Cox analysis showed that gender, age, current smoking, diabetes mellitus, history of renal disease, history of stroke, and SV1+ RV5 were significantly related to the occurrence of cardiovascular events. Kaplan - Meier curves showed that increasing SV1+ RV5 values were associated with higher incidences of cardiovascular events., Conclusions: ECG LVH is strongly related to cardiovascular events in elderly hypertensive patients.

Background: The widespread use of transesophageal echocardiography (TEE) is limited by disadvantages, including patient intolerance and increased medical costs. We aimed to investigate the feasibility and safety of transnasal TEE in the detection of possible embolic sources in patients with atrial fibrillation (AF) and/or stroke, using an ultrathin TEE probe., Methods: Sixty-two patients with AF and/or stroke underwent transnasal TEE without conscious sedation. The presence or the absence of the following parameters was evaluated: left atrial (LA) thrombus; LA spontaneous echocardiographic contrast; intraatrial shunts; and aortic plaque., Results: The insertion of a TEE probe was successful in 52 (84%) patients. TEE found LA thrombus in 10 (19%) patients and other embolic sources in 4 (8%) patients. Two (4%) patients had mild epistaxis., Conclusions: This study demonstrated that the use of transnasal TEE was feasible and safe in the detection of LA thrombus in patients with AF and/or stroke.

Objective: The elastic properties of the carotid arterial wall have not been directly characterized in the clinical setting. Strain rate (SR) imaging is a newly developed echocardiographic method developed for imaging the tissue motion of the myocardium. The purpose of this study was to directly estimate the elastic properties of the carotid artery by using SR imaging in patients with coronary artery disease (CAD)., Methods: A total of 135 patients with CAD, 15 age-matched controls, and 35 young healthy subjects had a carotid ultrasound examination for measuring the values of SR and strain of the carotid artery. The intima-media thickness and distensibility coefficient of the carotid artery were estimated., Results: Age and Framingham risk score were significantly related to SR and strain, respectively (r = 0.62-0.67, all P < .001). These strain measurements were significantly correlated with distensibility coefficient and intima-media thickness, respectively (r = 0.30-0.56, all P < .001). Similar values of the areas under the receiver operating characteristic curves were obtained among Framingham risk score (0.70 +/- 0.05), SR (0.67 +/- 0.05), and strain (0.73 +/- 0.05)., Conclusion: This study demonstrated that the elastic properties of the carotid artery wall were directly characterized by using SR imaging in patients with CAD.

Background: A pocket-sized portable transthoracic echocardiographic (pTTE) imaging device is commercially available, but its feasibility and accuracy in the assessment of cardiac chamber size and function has not been fully compared with the results of standard TTE (sTTE) examination., Methods and Results: The target population comprised 125 unselected patients who underwent sTTE and pTTE examinations. The left ventricular (LV) diastolic and systolic dimensions, fractional shortening (FS), the thickness of the interventricular septum (IVS) and of the LV posterior wall (PWT), left atrial (LA) dimension, and ascending aorta diameter were measured. Echocardiographic measurements were completed for both pTTE and sTTE in all patients (feasibility 100%). LV dimensions, FS, IVS, PWT, LA dimension, and aorta diameter obtained by pTTE showed excellent correlation and agreement with sTTE (r=0.87-0.98, all P<0.001). Observer variabilities for these measurements were similar between pTTE and sTTE., Conclusions: In the present study, pTTE with the Acuson P10 was feasible and accurate for assessing cardiac chamber size and function.

Background: Although multidetector computed tomography (MDCT) allows non-invasive assessment of coronary artery stenosis, the presence of calcified lesions often lead to an overestimation of the stenosis. The present study was an evaluation of whether enhancement of first-pass myocardial data can improve the diagnostic accuracy of 64-MDCT., Methods and Results: Data from 70 patients with single-vessel disease who underwent 64-MDCT followed by catheter-based coronary angiography (CAG) were analyzed. Myocardial enhancement was quantified by exaimining the signal densities at diastole. Among a total of 83 plaque segments, 35 calcified plaque segments were detected and 46 segments were found to have more than 50% coronary stenosis on catheter-based CAG. The average diameter stenosis was 75.2+/-12.8%. Diagnosis by 64-MDCT of significant stenosis (segment-based analysis) had a sensitivity, specificity and accuracy for segments without calcified lesions of 92%, 100% and 99.7%, respectively, and 95.2%, 50%, and 77.1%, respectively, for calcified lesions. Taking into account the myocardial enhancement by calculating the decrease of the standardized signal densities in percent, these parameters could be improved to 95.2%, 85.7% and 91.4%, respectively, for segments with calcified lesions., Conclusions: The diagnostic accuracy of 64-MDCT for stenosis with calcified lesions in particular can be improved by taking into account the myocardial enhancement data.

Background: Cardiovascular disease is the most frequent cause of death and disability for diabetic patients, and patients with diabetes are more likely to have silent ischemia. Multi-detector computed tomography (MDCT) allows non-invasive assessment of coronary artery stenosis and plaque properties. In this study, we investigated whether 64-slice MDCT can non-invasively identify significant coronary artery stenosis in asymptomatic, type 2 diabetes mellitus (T2DM) and impaired glucose tolerance (IGT) patients., Methods and Results: The study population consisted of 154 consecutive asymptomatic patients [IGT (n=93), T2DM (n=61)]. All patients underwent contrast-enhanced 64-slice MDCT. The number of diseased coronary segments was classified as showing obstructive (> or = 50% luminal narrowing) disease or not. Significant coronary stenosis was detected in 43 (27.9%) of 154 enrolled patients. Patients with T2DM showed significantly more coronary stenosis than patients with IGT (41% vs. 19.4%; p<0.01). Twenty-three patients [14.9%; IGT (n=9), T2DM (n=14)] underwent percutaneous coronary intervention (PCI) for severe stenosis. Patients with T2DM showed significantly more calcified plaque than IGT (47.5% vs. 29%; p<0.05), but not significantly more soft plaque (19.7% vs. 15.1%; ns), or significantly different remodeling index (1.05+/-0.18 vs. 1.04+/-0.21; ns), respectively., Conclusions: 64-Slice MDCT can non-invasively identify significant coronary artery stenosis in asymptomatic, T2DM and IGT patients.

Background: Recent advancements in 16-slice multidetector-row computed tomography (16-slice MDCT) provide for non-invasive assessment of not only coronary artery disease (CAD), but also myocardial properties and the anatomy of the whole heart. The purpose of the present study was to investigate whether the aortic valve area (AVA) in patients with aortic stenosis (AS) assessed by 16-slice MDCT corresponds to echocardiographic assessment and to evaluate simultaneously the clinical accuracy in detecting CAD with 16-slice MDCT., Methods and Results: The AVA of 29 consecutive AS patients with transthoracic echocardiography (TTE) and 16-slice MDCT were analyzed. The AVA was estimated by means of the continuity equation method in 2-dimensional echocardiography (DE) and the quantitative planimetric method after multi-planar reformation in 16-slice MDCT. Concomitantly, the severity of the coronary artery stenosis was assessed by 16-slice MDCT. In the present study, the AVA assessed by TTE and 16-slice MDCT was 1.34+/-0.32 cm(2) and 1.38+/-0.32 cm(2), respectively. Regression analysis showed that the AVA in patients with AS determined by 16-slice MDCT correlated well with those determined by 2-DE (r=0.96, p<0.001). Significant coronary artery stenosis of more than 50% diameter reduction was present in 48% of the study population., Conclusions: In patients with AS, the analysis of the severity of the AVA by 16-slice MDCT provides a feasible and accurate estimation with the concomitant evaluation of CAD.

Background: Ventricular remodeling is an independent predictor of left ventricular function in patients with myocardial infarction (MI). Accelerated ventricular remodeling is a probable contributor to the increased mortality observed after MI in hypertensive patients. The purpose of this study is to assess the relationship of antecedent hypertension to ventricular remodeling after MI., Methods: Seventy-nine patients presenting with a first acute MI (AMI) who were treated and attained Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 with re-perfusion therapy within 12 hours of their symptom onset were enrolled in this study. All of them underwent left ventriculography (LVG) immediately after re-perfusion therapy and again at 6 months after the occurrence of MI. Patients were divided into two groups; hypertensive group and normotensive group. End-diastolic volume index (EDVI), end-systolic volume index (ESVI), and EF were compared between acute phase and 6 months after AMI in each group., Results: The hypertensive group showed a significant increase in both EDVI and ESVI after 6 months, whereas the normotensive group did not. In addition, there was no change in EF in the hypertensive group, whereas EF increased significantly after 6 months in the normotensive group. As a result, percent change in ESVI and EF showed significantly differences between the hypertensive group and normotensive group, whereas percent change in EDVI showed no significant difference between the two groups., Conclusions: Antecedent hypertension interacts with ventricular remodeling after MI.

Background: Microvascular damage immediately after reperfusion therapy is an independent predictor of left ventricular function in patients with acute myocardial infarction (AMI). However, its recovery may vary among individuals and the relationship between convalescent stage microvasculature and late myocardial morphologic change is unclear., Methods and Results: Patients treated with coronary angioplasty within 12 h of their first anterior AMI were enrolled in this study. Coronary flow reserve (CFR) was measured 3 weeks post AMI, in both branches of the left coronary artery: culprit (left anterior descending artery: LAD) and non-culprit (left circumflex artery: LCX). Left ventriculography was performed at 3 weeks and 6 months post AMI and compared. Seventeen patients showed abnormal CFR in the LAD (Group 1: CFR<2), whereas 20 patients showed normal CFR (Group 2: CFR >/=2). Percent changes of end-diastolic volume tended to be higher in Group 1 than in Group 2 (11.8+/-21.6% vs -1.3+/-14.4%, p=0.056), and %changes of end-systolic volume was significantly smaller in Group 2 (11.8+/-22.1% vs -8.7+/-25.1%, p<0.05). A statistically significant correlation was found between absolute and relative CFR in the LAD and %change of end-systolic volume (r=-0.58: p<0.001, and r=0.40: p<0.05, respectively)., Conclusions: Microvascular function in the convalescent stage may be related to these favorable changes.

Hepatocyte growth factor (HGF) is a well-known powerful proliferative factor of vascular endothelial cells and it has been reported that plasma HGF concentrations are increased in acute myocardial infarction (AMI), although the mechanisms are not yet well delineated. Serum HGF levels and C-reactive protein (CRP) were measured in 22 patients with unstable angina pectoris (UAP) (15 males, 7 females; class IIb or IIIb of the Braunwald classification), 60 patients with AMI (37 males, 23 females; average time from the onset of symptoms to admission 4.6+/-0.7h, range, 0.5-12h), and 20 normal subjects. Immediate angioplasties were performed in 51 patients with AMI, and the time course of the HGF levels were measured in 31 patients among them. Heparin dramatically increased the HGF level and it declined to the normal range 18h after heparin injection. Blood samples were taken before heparin treatment, or at least 24h after. Serum HGF levels on admission was significantly increased in UAP (mean+/-SE: 0.30+/-0.03ng/ml, p<0.01), and AMI (0.27+/-0.02ng/ml, p<0.01) compared with the normal subjects (0.19+/-0.01 ng/ml). Even in the early stage (within 3 h of onset of symptoms to admission, average time was 1.8+/-0.1 h), serum HGF levels were already elevated (0.25+/-0.02 ng/ml, p<0.05). There was no significant difference between the HGF levels in UAP and AMI. Fifty-one of the 60 patients with AMI underwent immediate percutaneous transluminal coronary angioplasty and blood samples were obtained from 31 of them on days 7, 14, and 21 after MI. Serum HGF levels peaked on day 7 (0.34+/-0.04ng/ml, p<0.01) and there was a weak relationship between peak creatine kinase and serum HGF levels at that time. A statistically significant correlation was found between peak CRP and serum HGF levels on day 7 (r=0.62: p<0.001). Serum HGF levels decreased to nearly normal by day 21 (0.22+/-0.01 ng/ml). The study shows that serum HGF levels during the early stage of AMI increased significantly and peaked by day 7 after the onset, at which time there was a strong correlation with peak CRP levels. These data suggest that HGF production may be related to the inflammatory response in AMI.