Background: Obesity is related to left ventricular (LV) diastolic dysfunction, although its pathophysiological mechanism remains unclear. Epicardial adipose tissue (EAT) is an ectopic fat with paracrine effects on coronary circulation and myocardium. We hypothesized that left ventricleespecific (periventricular) EAT may deteriorate diastolic function by impairing coronary microcirculation. Methods: In protocol 1, 74 patients without obstructive narrowing of the left anterior descending artery on multidetector computed tomography (MDCT) underwent coronary flow reserve (CFR) examination to evaluate the relationship between EAT and coronary microcirculation. In protocol 2, 372 patients who underwent both MDCT and serial transthoracic Doppler echocardiographic (TTDE) examinations were enrolled to investigate the impact of periventricular EAT on changes in diastolic function. EAT volume was measured by MDCT. CFR and diastolic function were assessed by TTDE. Deterioration of LV diastolic function was defined as a >= 20% decrease in early diastolic mitral annular velocity. Results: CFR was significantly correlated with periventricular EAT volume (r = -0.37; P = 0.001), but not with total EAT volume (r = -0.21; P = 0.071). Periventricular EAT volume (P = 0.010) was significantly associated with CFR independent of cardiovascular risk factors. Among the 372 patients who had serial TTDE examinations, the frequency of deteriorated LV diastolic function was lowest in the lower tertile of periventricular EAT, intermediate in the middle tertile, and highest in the upper tertile (12.9%, 21.0%, and 25.8%, respectively; P = 0.037). Age, diabetes mellitus, and periventricular EAT volume were significantly associated with deterioration of LV diastolic function (all P < 0.05). Conclusions: This study demonstrated the close association of periventricular EAT with impaired CFR and deteriorated LV diastolic function.

Background: There is conflicting evidence for the link between calcification and plaque instability. Intravascular ultrasound (IVUS) studies have shown that calcified plaques are associated with stable plaques. In contrast, recent histopathological studies have revealed that plaque calcification is present in 69% of ruptured plaques in sudden coronary death. Furthermore, studies using electron-beam computed tomography have reported that calcium score relates to acute coronary events. The purpose of this study is to investigate the relationship between patterns of calcification and arterial remodeling of culprit lesions, comparing patients with acute coronary syndromes (ACS) with those with stable angina (SAP). Methods and Results: Preinterventional intravascular ultrasound (IVUS) images of 178 patients were studied; 61 with acute myocardial infarction (AMI), 70 with unstable angina pectoris (UAP) and 47 with SAP. The presence of calcifications within an arc of less than 90° for all calcifications was significantly higher in patients with either AMI or UAP than in SAP (P<0.0001). Moreover, the average number of calcium deposits within an arc of less than 90° per patient was significantly higher in AMI than in SAP (P<0.0005) (AMI: 1.4±1.3, SAP: 0.5±0.8, mean±SD). Conversely, the length of the calcium deposits was significantly longer in SAP patients (P<0.0001) (AMI: 2.2±1.6, UAP: 1.9±1.8, SAP: 4.3±3.2, mean±SD). In AMI patients, the typical pattern was spotty calcification, associated with a fibrofatty plaque and positive remodeling. In ACS patients showing negative remodeling, no calcification was the most frequent. Conversely, in SAP patients, the frequency of extensive calcification was the highest. Conclusion: These findings show that IVUS allows the identification of vulnerable plaques in coronary arteries, not only by identifying a large lipid core and positive remodeling, but also by identifying a spotty pattern of calcification.

症例は84歳，女性．2007年より複数の欠損孔を有する心房中隔欠損を指摘されており，2015年3月にうっ血性心不全のため入院となった．その際，肺体血流比が1.8であり，心不全を併発していたことから外科的治療を勧められたが，高齢を理由に希望しなかった．同年8月に急性下壁梗塞の診断で緊急入院となり，冠動脈造影検査で右冠動脈の近位部に完全閉塞を認めた．同部位に対して経皮的冠動脈インターベンションを施行され，入院後の第1病日にはバイタルサインは安定していた．しかし，第2病日に急激に呼吸状態が悪化した．経胸壁心エコー図検査にて心房中隔欠損孔を通して新たに右左シャントが生じており，これに伴う低酸素血症と考えられた．再度外科的治療を勧められたが，ご家族は希望されなかった．内科的治療を継続したが，治療の甲斐なく他界した．右室梗塞の経過中に卵円孔開存や心房中隔欠損を介した右左シャントを生じた例はこれまでにも報告されているが，本症例では解剖学的な要因も関与していた可能性がある．たとえば，心房中隔の伸展とそれに伴う下大静脈の血流方向の変化，ペースメーカーリードによる三尖弁逆流ジェットの偏位である．これらのことを踏まえた上で，考察も交えて報告する．

Background: Chronic kidney disease (CKD) is strongly associated with coronary artery disease (CAD), although the underlying pathophysiological mechanism remains unclear. Epicardial adipose tissue (EAT) has recently been recognized as an important source of various pro-inflammatory cytokines causing coronary atherosclerosis. This study investigated the relationship between CKD and EAT volume in association with high-risk plaque.Methods and Results: The study included 275 patients with an estimated glomerular filtration rate (eGFR) >= 30 ml/min/1.73 m(2) who underwent multidetector computed tomography (MDCT) for the evaluation of CAD. Patients were classified, according to eGFR, into a CKD group (30 <= eGFR<60 ml/min/1.73 m(2)) or a non-CKD group (eGFR >= 60 ml/min/1.73 m(2)). MDCT was used to assess coronary plaque morphology and EAT volume. One hundred and ten patients with CKD were more likely to be older, have higher prevalence of hypertension, lower serum HDL-C, higher serum CRP, and larger EAT volume, than those without CKD (all P<0.01). On multivariate analysis age, hypertension, and EAT volume were significantly associated with eGFR (all P<0.01). EAT volume was associated with the presence of high-risk plaque, independent of traditional CAD risk factors (P=0.003).Conclusions: Patients with CKD had significantly increased EAT volume, which could be associated with the presence of high-risk plaque.

Introduction: Visit-to-visit variability in systolic blood pressure (SBP) has been reported as a risk of long-term cardiovascular events in hypertensive patients. However, a little has been known t...

Background Remote ischemic conditioning (RIC) is a treatment modality that suppresses inflammation and improves endothelial function, which are factors involved in the pathogenesis of heart failure (HF) with reduced left ventricular ejection fraction. Coronary flow reserve (CFR) is a physiological index of coronary microcirculation and is noninvasively measured by transthoracic Doppler echocardiography (TTDE). This study aimed to investigate the effects of RIC on CFR in healthy subjects and patients with HF, through the assessment by TTDE. Methods Ten patients with HF with left ventricular ejection fraction of less than 40%, and ten healthy volunteers were enrolled in this study. RIC treatment was performed twice a day for 1 week. Our custom-made RIC device was programmed to automatically conduct 4 cycles of 5 minutes inflation and 5 minutes deflation of a blood pressure cuff to create intermittent arm ischemia. CFR measurements and laboratory tests were examined before, and after 1 week of RIC treatment. Results One week of RIC treatment was well tolerated in both groups. RIC treatment increased CFR from 4.0±0.9 to 4.6±1.3 (mean ± standard deviation) in healthy subjects (P=0.02), and from 1.9±0.4 to 2.3±0.7 in patients with HF (P=0.03), respectively. Systolic blood pressure in healthy subjects, and heart rate in HF patients decreased after RIC treatment (both P<0.01). Conclusion This study demonstrated that a 1 week course of RIC treatment improved coronary microcirculation in healthy subjects and patients with HF associated with reduced left ventricular ejection fraction.

Introduction: 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 impact of changes in EAT accumulation on CAD prognosis remains unclear. This study aimed to investigate whether an increase of EAT volume predicts future acute coronary syndrome (ACS) events in non-obese CAD patients. Methods: This study consisted of 517 non-obese CAD patients who underwent serial multidetector computed tomography (MDCT) examinations to evaluate coronary atherosclerosis progression. All patients received comprehensive management to reduce CAD risk factors after the first MDCT examination. MDCT was repeated at 6-24 months and patients were followed-up for more than 1 year or until ACS events occurred. Results: Of 517 patients, EAT volume increased >10ml from first to second MDCT examination in 159 (31%) patients, decreased >10 ml in 91 (18%). In remaining 267 (51%) patie...

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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

OBJECTIVES The aim of this study was to determine the predictive value of the napkin-ring sign on coronary computed tomography angiography (CTA) for future acute coronary syndrome (ACS) events in patients with coronary artery disease.BACKGROUND Recent studies have reported a close association between the napkin-ring sign on coronary CTA and thin-cap fibroatheroma.METHODS The subjects of this prospective study were 895 consecutive patients who underwent coronary CTA examination and were followed for >1 year. The primary endpoint was an ACS event (cardiac death, nonfatal myocardial infarction, or unstable angina pectoris). The coronary CTA analysis included the presence of obstructive plaque, positive remodeling (PR), low-attenuation plaque (LAP), and the napkin-ring sign. The napkin-ring sign was defined by the following criteria: 1) the presence of a ring of high attenuation around certain coronary artery plaques; and 2) attenuation of the ring presenting higher than those of the adjacent plaque and no >130 Hounsfield units.RESULTS Of the 12,727 segments, 1,174 plaques were observed, including plaques with PR in 130 segments (1.0%), LAP in 107 segments (0.8%), and napkin-ring signs in 45 segments (0.4%). Thirty-six of the 45 plaques with napkin-ring signs (80%) overlapped with those showing either PR or LAP. During the follow-up period (2.3 +/- 0.8 years), 24 patients (2.6%) experienced ACS events, and plaques developed in 41% with a napkin-ring sign. Segment-based Cox proportional hazards models analysis showed that PR (p < 0.001), LAP (p = 0.007), and the napkin-ring sign (p < 0.0001) were independent predictive factors for future ACS events. Kaplan-Meier analysis demonstrated that plaques with napkin-ring signs showed a higher risk of ACS events compared with those without a napkin-ring sign.CONCLUSIONS The present study demonstrated for the first time that the napkin-ring sign demonstrated on coronary CTA was strongly associated with future ACS events, independent of other high-risk coronary CTA features. Detection of the napkin-ring sign could help identify coronary artery disease patients at high risk of future ACS events. (J Am Coll Cardiol Img 2013;6:448-57) (C) 2013 by the American College of Cardiology Foundation

AIMSIncreasing clinical evidence has emphasized the importance of coronary plaque characteristics, rather than the severity of luminal narrowing on acute coronary syndrome (ACS) outcome. Computed tomographic coronary angiography (CTCA) is a unique, non-invasive approach for assessing plaque characteristics. This study was prospectively designed to investigate the prognostic value of physiologically non-obstructive but a vulnerable coronary plaque on CTCA for predicting future ACS events.METHODS AND RESULTSThis study consisted of 543 patients who had undergone CTCA and had normal findings on exercise-stress myocardial perfusion single-photon emission computed tomography. CTCA analysis included the presence of >50% luminal stenosis and vulnerable features including positive remodelling (PR), low-attenuation plaque, and ring-like sign. The primary endpoint was ACS events including cardiac death, non-fatal myocardial infarction, and unstable angina. The mean follow-up period was 3.4 ± 0.8 years. The 3-year cumulative event rate was 1.2% per year, and 87% of ACS events occurred in plaques with at least one of vulnerable features. In patient-based multivariate analysis, the presence of plaque with vulnerable features on CTCA was a significant predictor for future ACS events (P = 0.001). Patients with vulnerable plaque had worse ACS outcomes compared with those without vulnerable plaques (3-year cumulative event rate; 3.2 per year vs. 0.8%, P < 0.001).CONCLUSIONThis study demonstrated that physiologically non-obstructive but vulnerable coronary plaques were associated with future ACS events. We should pay more attention to currently non-obstructive plaque but showing vulnerable morphologies on CTCA.

BACKGROUND: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.

AIMS:Spontaneous coronary artery dissection (SCAD) found typically in young females without classical coronary risk factors is thought to be a very rare cause of acute coronary syndrome (ACS). The prevalence of SCAD in ACS subjects has been unclear, probably due to the nature of coronary angiography. The aim of this study was to use optical coherence tomography (OCT) to investigate the prevalence of SCAD in ACS.METHODS AND RESULTS:This study consisted of 326 patients with ACS (with or without ST-segment elevation) who underwent OCT to explore the entire culprit artery. According to OCT findings, patients were divided into a SCAD, a plaque rupture (PR), and a non-SCAD/non-PR group. OCT revealed 13 (4.0%) SCADs and 160 (49.1%) plaque ruptures in ACS subjects. The percentage of females versus males was greater in the SCAD group (SCAD: 53.8% vs. PR: 20.0% vs. non-SCAD/non-PR: 23.5%, p=0.02) while no difference was observed in age (SCAD: 67.3±13.3 vs. PR: 66.5±11.1 vs. non-SCAD/non-PR: 67.0±10.5, p=0.90). The prevalence of dyslipidemia (SCAD: 30.8% vs. PR: 63.8% vs. non-SCAD/non-PR: 67.5%, p=0.03) and current smoking (SCAD: 7.7% vs. PR: 57.9% vs. non-SCAD/non-PR: 59.7%, p<0.01) were significantly lower in the SCAD group.CONCLUSIONS:SCAD is not a rare cause for ACS, especially in females without classical coronary risk factors.

BACKGROUND:Atrial fibrillation (AF) is associated with considerable morbidity and mortality in patients with coronary artery disease (CAD). Epicardial adipose tissue (EAT) is recognized as an important inflammatory tissue that may exert deleterious effects on the adjacent left atrial (LA) wall. Multidetector computed tomography (MDCT) can accurately assess EAT's volume and distribution. This study used MDCT to investigate the effect of peri-atrial EAT on new-onset nonvalvular AF.METHODS AND RESULTS:The study group consisted of 279 patients (176 men; age, 65±10 years) with no history of AF who underwent MDCT examination for evaluation of CAD. EAT was automatically identified on the basis of threshold attenuation values of -30 to -250 Hounsfield units. EAT volume was calculated as the sum of EAT area and subsequently divided into peri-atrial and peri-ventricular EAT. During follow-up of 3.3±1.0 years, AF occurred in 17 (6.1%) patients. Cox proportional hazards regression analysis indicated that male sex, and the LA and peri-atrial EAT volumes (P=0.03, P<0.001, and P<0.001, respectively) were independent predictors for future AF. The sensitivity and specificity for the prediction of AF using a peri-atrial EAT volume index of ≥27 ml/m(2) were 88% and 92%, respectively.CONCLUSIONS:This is the first study demonstrating that peri-atrial EAT volume estimated by MDCT excellently predicted the development of new-onset AF in patients with CAD, independent of LA enlargement.

BackgroundArterial hypertension is an established risk factor for acute coronary syndrome (ACS). Multidetector computed tomography (MDCT) is an accurate and less invasive technique for assessment of the degree of coronary artery luminal narrowing and characterization of coronary atherosclerosis. We therefore aimed to investigate the predictive power of MDCT for future ACS events and compared with traditional parameters in patients with hypertension.MethodsOne hundred and thirty-four patients (93 men, mean age 70 ± 11 years) with hypertension underwent MDCT for evaluation of coronary artery disease. MDCT analysis focused on the presence of plaques, the degree of stenosis, and the plaque characteristics. Traditional parameters included Framingham risk score, carotid intima-media thickness, and left ventricular mass index.ResultsDuring a mean follow-up of 39 ± 10 months, ACS events occurred in 10 patients, including myocardial infarction (n = 3) and unstable angina (n = 7). Multivariate analysis identified total number of low attenuation plaques as an independent predictor of ACS events (p < 0.001).ConclusionWe demonstrated that non-obstructive low attenuation coronary plaques on MDCT predicted more accurately future ACS events in patients with hypertension than traditional parameters.

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.

Background: Arterial stiffness (AS) is a strong predictor of cardiovascular disease (CVD) in patients with hypertension (HT), which is modified by the medications for HT and other atherosclerotic risk factors. Cardio-ankle vascular index (CAVI) provides noninvasive, objective information of the overall AS from the origin of the aorta to the ankle, independent of blood pressure. This study aimed to investigate changes of CAVI after comprehensive management for atherosclerotic risk factors and its impact on future CVD outcome in patients with HT. Methods: This study consisted of 162 patients with HT (68±9 years, 117 men) those CAVI were impaired. CAVI test was repeated 6 months later. In addition, 100 healthy subjects (66±8 years, 79 men) were served as controls in order to estimate normal value of CAVI. All patients were followed for more than 1 year or until the occurrence of CVD event defined as cardiac death, non-fatal myocardial infarction, unstable angina, ischemia-driven revascularization and stroke. Results: Based on the results of control subjects, impaired CAVI was defined as >8.7 (mean plus 1 SD of controls). Of the 162 patients, CAVI improved 6 months later in 82 (51%), whereas impaired CAVI was sustained in remaining 80 (49%). During the follow-up (2.4±1.2 years) after second CAVI test, CVD events occurred in 19 (12%) patients. Framingham risk score (p=0.027), multi-vessel coronary disease (p=0.03) and persistently impaired CAVI (p=0.033) were independent predictors for future CVD events, independent of baseline CAVI. Patients with persistently impaired CAVI had worse CVD outcomes as compared to those with improved CAVI (p Conclusions: This study demonstrated for the first time that impaired AS, as estimated by CAVI, did not improved even after comprehensive management of HT and other risk factors in approximately half of patients with HT. Serial measurement of CAVI, not a single-time, provides prognostic information in patients with HT.

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.