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The patient was a 73-year-old male with a history of hypertension, diabetes mellitus, dyslipidemia, rheumatoid arthritis, repeated percutaneous coronary intervention and percutaneous peripheral intervention procedures. He was frequently admitted to our hospital for congestive heart failure with orthopnea. The myocardial washout rate of iodine-123-β-methyl iodophenyl-pentadecanoic acid was defective on scintigraphy. He was diagnosed with triglyceride deposit cardiomyovasculopathy (TGCV). Proton magnetic resonance spectroscopy (1H-MRS) indicated the level of myocardial triglyceride (TG) content to be extremely high (4.92%). This is the first report to confirm a massive accumulation of TG in the myocardium of a patient with TGCV using 1H-MRS noninvasively.

Background/Introduction Acute heart failure (AHF) is one of the major causes of mortality, and identifying the patients at high risk of mortality at the time of admission is crucial to improve clinical outcomes. Although some risk prediction models for patients with AHF have been proposed mainly from randomized clinical trials, the patients in such studies tend not to be similar to those in the real world. Recently, BIOSTAT risk score and AHEAD score derived from two large-scale registry dataset are proposed as useful risk stratification tools for patients with AHF. However, these scores have not been well externally validated and their prognostic prediction performance has not been directly compared. Purpose To validate and compare prognostication of BIOSTAT risk score and AHEAD score in AHF patients. Methods Patients who consecutively admitted to the cardiac intensive-care unit in our institution with a diagnosis of AHF from 2007 to 2011 were analyzed. Among them, patients with acute coronary syndrome, dialysis, malignancy were excluded. BIOSTAT risk score was calculated using 5 factors (age, blood urea nitrogen, BNP, hemoglobin, prescription of beta blockers), and AHEAD score was also calculated with 5 factors (atrial fibrillation, hemoglobin, age, creatinine, and diabetes mellitus). We also developed AHEAD + BNP model incorporating BNP into AHEAD score. Endpoint was 1-year all-cause death. Results Overall, 591 eligible patients were enrolled (mean age was 70±14 years old, 64.8% were male) and 96 patients (16.2%) died during the follow-up of 1-year. The median [interquartile range] of AHEAD score and BIOSTAT risk score were 2 [1–3] and 3 [2–4], respectively. The areas under the curves of receiver operating characteristic curve (AUC) were 0.66 for AHEAD, 0.68 for AHEAD + BNP, and 0.72 for BIOSTAT, respectively. The calibration plots for AHEAD, AHEAD + BNP, and BIOSTAT models showed good calibration (Hosmer-Lemeshow test: p=0.89, 0.74, and 0.74, respectively). The BIOSTAT model's AUC was significantly higher compared to AHEAD (p=0.018) and marginally statistically higher compared to AHEAD + BNP (p=0.054). However, BIOSTAT model showed statistically significant net reclassification improvement compared to both AHEAD (NRI: 0.43, p Conclusion The BIOSTAT score comprised of five readily available clinical variables predict 1-year mortality of patients with AHF with good discrimination and calibration. ROC curves Funding Acknowledgement Type of funding source: None

Background/Introduction; A rapid rule-out or rule-in protocol based on the 0-h/1-hour algorithm using high-sensitivity cardiac troponin T (hs-cTnT) is recommended by the European Society of Cardiology (ESC). Around 40–50% were stratified into “rule-out” group, and their 30-days prognosis was excellent. However, the one-year prognosis is uncertain. We aimed to better characterize these patients. Methods This study was a prospective, multi-center, observational study of patients with suspected non-ST elevation acute coronary syndrome (NSTE-ACS) admitted to 5 hospitals in Japan and Taiwan from 2014 November to 2018 December, respectively. All patients underwent a clinical assessment the included medical history, physical examination, 12-lead ECG, standard blood test, chest radiography. Exclusion criteria were ST elevated myocardial infarction, chronic kidney disease (serum creatinine more than 3 mg/dL) and congestive heart failure, arrhythmia, or infection disease. The patients were divided into three groups according to the algorithm; “rule-out”, “observe” and “rule-in”. The final diagnosis was then adjudicated by 2 independent cardiologists using all available information, including coronary angiography, coronary computed tomography, stress electrocardiography and follow-up data. The presence of acute myocardial infarction (AMI) was defined according to the Fourth Universal Definition of Myocardial Infarction. After hospital discharge patients were follow after one-year b telephone or in written form. Major adverse cardiovascular events (including death myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention (PCI)) were recorded by establishing contact with the patient and the family physicians. The primary prognosis end point was all-cause mortality. Results Of the 1,187 patients were analyzed after exclusion. The prevalence rate of AMI was 16.1%. According to the algorithm, 42% (n=493) of patients were assigned to “rule-out” group and had no AMI nor death. The most common final adjudicated diagnoses were atypical chest pain (80%), gallstone attack (3%) and vasospastic angina pectoris (2%). All patients with unstable angina (4.7%) underwent PCI. Conclusion(s) Our findings suggest that the “rule-out” group patients according to ESC 0-h/1-hour algorithm provides very high safety and efficacy for the triage toward AMI. Funding Acknowledgement Type of funding source: None

Objectives To determine the seroprevalence of anti-SARS-CoV-2 IgG and IgM antibodies in symptomatic Japanese COVID-19 patients. Methods Serum samples (n = 114) from 34 COVID-19 patients with mild to critical clinical manifestations were examined. The presence and titers of IgG antibody for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were determined by a chemiluminescent microparticle immunoassay (CMIA) using Alinity i SARS-CoV-2 IgG and by an immunochromatographic (IC) IgM/IgG antibody assay using the Anti-SARS-CoV-2 Rapid Test. Results IgG was detected by the CMIA in 40%, 88%, and 100% of samples collected within 1 week, 1–2 weeks, and 2 weeks after symptom onset in severe and critical cases, and 0%, 38%, and 100% in mild/moderate cases, respectively. In severe and critical cases, the positive IgG detection rate with the IC assay was 60% within one week and 63% between one and two weeks. In mild/moderate cases, the positive IgG rate was 17% within one week and 63% between one and two weeks; IgM was positive in 80% and 75% of severe and critical cases, and 42% and 88% of mild/moderate cases, respectively. On the CMIA, no anti-SARS-CoV-2 IgG antibodies were detected in COVID-19 outpatients with mild symptoms within 10 days from onset, whereas 50% of samples from severe inpatients were IgG-positive in the same period. The IC assay detected higher IgM positivity earlier from symptom onset in severe and critical cases than in mild/moderate cases. Conclusions A serologic anti-SARS-CoV-2 antibody analysis can complement PCR for diagnosing COVID-19 14 days after symptom onset.

Although subtraction coronary computed tomography angiography (S-CCTA) has recently been developed to improve the diagnostic ability in patients with severe calcification, increase in radiation exposure remains a concern. The usefulness of S-CCTA using a low-radiation dose protocol was investigated.S-CCTA in 320-row area detector CT was performed on 84 consecutive patients with suspected obstructive coronary artery disease with Agatston score ≥100. Reconstruction and radiation dose were changed according to the slow filling time (SF) (137.5msSF≤262.5ms. Half reconstruction without reduction of the current, 262.5msSF≤275ms: automatic patient motion correction with 50% reduction, SF≥275ms: full reconstruction with 70% reduction) at a tube voltage of 100kV. The percentage of patients with non-diagnostic stenosis of calcified coronary artery lesions was calculated in conventional (C-) CCTA, and S-CCTA was calculated based on 84 patients (446 segments) bases. In 27 patients (137 segments) examined by invasive coronary angiography (ICA), the diagnostic ability was investigated regarding the ICA findings as reference standard.The percentage of non-diagnostic patients and segments on C-CCTA vs. S-CCTA was 40.5% vs. 9.5% and 16.4% vs. 2.9%, respectively. The Agatston score was 589.3±655.3, and the total effective radiation dose (non-contrast scan and C-CCTA) was 2.7±1.1mSv. In the 27 patients, 137 segments area under the curve of S-CCTA (0.939, 95% CI: 0.895-0.983) for the ICA findings as reference standard was significantly higher than that of C-CCTA (0.785, 95% CI: 0.713-0.858) (p0.0001).The diagnostic ability of S-CCTA performed following the low-radiation dose protocol for patients with calcification was superior to that of C-CCTA alone.

Introduction Injury and loss of the endothelial glycocalyx occur during the early phase of sepsis. We previously showed that antithrombin has a protective effect on this structure in vitro. Here, we investigated the possible protective effects of antithrombin in an animal model of sepsis. Methods Wistar rats were injected with endotoxin, and circulating levels of syndecan-1, hyaluronan, albumin, lactate and other biomarkers were measured in an antithrombin-treated group and an untreated control group (n = 6 in each group). Intravital microscopy was used to observe leukocyte adhesion, microcirculation, and syndecan-1 staining. Results The circulating levels of syndecan-1 and hyaluronan were significantly reduced in the antithrombin-treated group, compared with the untreated controls. Lactate levels and albumin reduction were significantly attenuated in the antithrombin-treated group. Intravital microscopic observation revealed that both leukocyte adhesion and blood flow were better maintained in the treatment group. The syndecan-1 lining was disrupted after endotoxin treatment, and this derangement was attenuated by treatment with antithrombin. Conclusion Antithrombin effectively maintained microcirculation and vascular integrity by protecting the glycocalyx in a rat sepsis model.

AIMS We evaluated diagnostic accuracy of CT-fractional flow reserve (CT-FFR) computed on-site with a new vendor workstation, against invasive FFR as the reference standard. METHODS AND RESULTS Retrospective analyses compared CT-FFR of 104 vessels with 30-90% diameter stenosis in 75 patients imaged using single-rotation 320 detector-row coronary CT angiography (CCTA) with invasive FFR performed within 90 days. Prospective ECG-gated CCTA included exposure of 70-99% of the R-R interval. CT-FFR was computed on-site within the same physical space as the CT scanner and reading room. The diagnostic accuracy of CCTA >50% and CT-FFR ≤0.8 to detect hemodynamically significant stenosis, defined as FFR ≤0.8, was determined, as was the correlation of CT-FFR to FFR and instantaneous wave-free ratio (iFR). Forty-four vessels (42.3%) had an invasive FFR ≤0.8. The sensitivity, specificity, positive, and negative predictive value of CT-FFR ≤0.8 vs. CCTA >50% to detect hemodynamically significant stenosis defined as FFR ≤0.8 were 90.9% vs. 70.5%, 78.3% vs. 43.3%, 75.5% vs. 47.7%, and 92.2% vs. 66.7%, respectively. Area under the curve of CT-FFR was significantly higher than CCTA >50% [0.85, 95% confidence interval (CI): 0.76-0.91 vs. 0.57, 95% CI: 0.47-0.67; P

Coenzyme Q10 (CoQ10) plays a potential role in the prevention and treatment of cardiovascular disease through improved cellular bioenergetics. Critical illness in the intensive care unit has been reported to be associated with decreased circulating CoQ10 levels, and we previously demonstrated the association of low CoQ10 levels with in-hospital mortality. However, the association of CoQ10 with the acute phase of cardiovascular disease and long-term mortality remains unclear. We enrolled 242 consecutive patients with cardiovascular disease admitted to the coronary care unit of Juntendo University Hospital to investigate the association between long-term mortality and serum CoQ10 levels. During a mean follow-up of 3.2 years, 58 patients died. The mean serum CoQ10 levels were significantly lower in the non-survivors than in the survivors (0.48 ± 0.27 vs. 0.58 ± 0.38 mg/L; p = 0.035). Compared with the patients with above-median CoQ10 levels (0.46 mg/L), the cumulative incidence of all-cause mortality was significantly higher in those with lower CoQ10 levels (p = 0.025). Multivariate Cox regression analysis further demonstrated that lower CoQ10 levels were associated with poor prognosis. Low serum CoQ10 levels during the acute phase of cardiovascular diseases were associated with long-term mortality in patients, suggesting the utility of low serum CoQ10 levels as a predictor and potential therapeutic target.

Background The European Society Cardiology guidelines recommend that a 0-hour/1-hour (0–1hr) algorithm using high sensitivity cardiac troponin T (hs-cTnT) improves the early triage of patients with suspected non-ST elevation acute coronary syndrome (NSTE-ACS). However, diagnostic uncertainty remains in the 25–30% of patients assigned to “observe” group. Purpose To establish a step wise risk score system using HEART score and 0-hour/1-hour algorithm to identify the low risk group from observation group. Methods This study was a prospective, multi-center, observational study of patients with suspected NSTE-ACS admitted to five hospitals in Japan and Taiwan from 2014 to 2018, respectively. We applied the algorithm and calculated HEART score simultaneously. Patients were divided into three groups according to the algorithm: hs-cTnT below 12 ng/L and delta 1 hour below 3 ng/L were the “rule out” group; hs-cTnT at least 52 ng/L or delta 1 hour at least 5 ng/L were in the “rule in” group; the remaining patients were classified as the “observe” group. All patients underwent a clinical assessment the included medical history, physical examination, 12-lead ECG, continuous ECG monitoring, pulse oximetry, standard blood test, chest radiography, cardiac and abdominal ultrasonography. Patients presenting with congestive heart failure, terminal kidney disease on hemodialysis state, arrhythmia, or infection disease (which causes to increase troponin level) were excluded. Thirty-day MACE was defined as acute myocardial infarction, unstable angina (UA), or death. Results Of the 1,332 patients enrolled, 933 patients were analyzed after exclusion. NSTE-ACS was the final diagnosis for 122 (13.1%) patients and none of death. The HEART score less than 4 points in observation groups identified as very low risk with a negative predictive value (NPV) of 98.1% (95% confidential interval (CI); 90.1%-100%) and sensitivity of 98.0% (95% CI; 89.6%-100%). There were only one patient (0.5%) with AMI. In case of the HEART score less than 5 points, it could also identify as very low risk with a NPV of 96.7% (95% CI; 90.8%-99.3%%) and sensitivity of 94.1% (95% CI; 83.8%-98.8%). There were only three patients (1.2%) with AMI. Conclusion A combination of HEART score and the 0-hour/1-hour algorithm strategy rapidly identified the patient in observation group of 30-day MACE including UA where nor further cardiac testing would be needed. Acknowledgement/Funding JSPS KAKENHI Grant Number JP18K09554

Background/Introduction Implementation of the 2015 ESC 0-hour/1-hour algorithm using high-sensitivity troponin (hs-cTn) T in Asian countries presents a challenge for clinical practice. Purpose We aimed to prospectively validate the 0-hour/1-hour algorithm in Asian countries. Methods We conducted a prospective, multi-center, international cohort already utilizing 0-hour/1-hour algorithm using hs-cTnT for evaluation of patients with suspected of non-ST elevation acute coronary syndrome (NSTE-ACS). All patients underwent a clinical assessment the included medical history, physical examination, 12-lead ECG, continuous ECG monitoring, pulse oximetry, standard blood test, chest radiography, cardiac and abdominal ultrasonography. Patients presenting with congestive heart failure, terminal kidney disease on hemodialysis state, arrhythmia, or infection disease (which cause to increase troponin level) were excluded. Patients were divided into three groups according to the algorithm: hs-cTnT below 12 ng/L and delta 1 hour below 3 ng/L were the “rule out” group; hs-cTnT at least 52 ng/L or delta 1 hour at least 5 ng/L were in the “rule in” group; the remaining patients were classified as the “observational” group. The final diagnosis was then adjudicated by 2 independent cardiologists using all available information, including coronary angiography, coronary computed tomography, stress electrocardiography and follow-up data. The presence of acute myocardial infarction (AMI) was defined according to the Fourth Universal Definition of Myocardial Infarction. Results Of the 1,332 patients enrolled in 2014 to 2018, 933 patients were analyzed after exclusion. AMI was the final diagnosis for 122 (13.1%) patients. The algorithm ruled out AMI in 401 patients with a negative predictive value and sensitivity of 100% (95% confidential interval [CI], 98.6%-100%) and 100% (95% CI, 94.0%-100%), respectively, in the rule-out group. None of the patients were diagnosed with AMI. Among the 211 patients classified into the rule-in group, 90 were diagnosed as having AMI. The positive predictive value and specificity were 43.1% (95% CI, 36.2%-50.2%) and 78.3% (95% CI, 74.5%-81.7%), respectively. The median length of hospital stay was 159 min (142–180) in rule out group. Conclusion(s) Our findings suggest that the 0-hour/1-hour algorithm using hs-cTnT provides very high safety and efficacy for the triage toward rapid rule-out to rule-in of AMI. Acknowledgement/Funding JSPS KAKENHI Grant Number JP18K09554

Background The usefulness of fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) evaluation has been confirmed in the determination of revascularization of coronary artery disease. When FFR≤0.8 and iFR≤0.89 were regarded as the criteria for positivity, the discordance was noted in approximately 20%, but this cause has not been well established. Purpose The purpose of this study was to investigate the patient background and features on coronary CT angiography (CCTA) showing the discordance between FFR≤0.8 and iFR≤0.89. Methods The subjects were consecutive 85 cases with 108 vessels in which stenosis of 30–90% was detected at one vessel of at least 2mm or more in the major epicardial vessels and FFR and iFR was performed within subsequent 90 days, among suspected cases of coronary arterial diseases which underwent CCTA. The factors showing the discordance between FFR and iFR (patient background, coronary artery calcification score, high risk plaque features on CCTA (positive remodeling, low attenuation plaque), plaque characteristics by a plaque analysis software using a new algorithm called labeling method (vessel volume, plaque volume, lumen volume, plaque length, maximum plaque burden, necrotic core area, fibrous area and calcium area) were evaluated using logistic regression analysis on per-patient and per-vessel basis. Results There were no significant both FFR and iFR positive definite factors on per-patient basis. The lumen volume/vessel volume (OR: 0.93, 95% CI: 0.88–0.98, P=0.0032) (OR: 0.90, 95% CI: 0.85–0.95, P Conclusions In both FFR and iFR, only lumen volume /vessel volume, MLA, plaque volume/vessel volume and plaque burden were significant positive definite factors. As for the discordance between FFR and iFR, PR is significant predictor in FFR positive and iFR negative group.

The purpose of the study was to evaluate the optimal cut-off value of CT-Fractional Flow Reserve (CT-FFR) using fluid–structure interaction and how to adjust the CT-FFR’s underestimation from a standpoint of minimize 1-year cardiac events. Subjects were 38 cases with 44 vessels in which stenosis of 30–90% was detected using one-rotation scanning by 320-row coronary CT angiography (CCTA) and invasive FFR (i-FFR) was performed within subsequent 90 days. CT-FFR was calculated using on-site from the multiple cardiac phases. A hypothetical 1-year cardiac event incidence was estimated using previous evidences when revascularization was decided based on CT-FFR. We assessed the optimal cut-off value of CT-FFR and how to correct the CT-FFR to minimize hypothetical cardiac events under four different disease prevalence (20%, 25%, 30%, 35%, and 40%). A total of 16 vessels had i-FFR ≤ 0.8. On per-patient basis, the sensitivity, specificity, positive predict value, negative predict value, and diagnostic accuracy of CT-FFR ≦ 0.8 vs CCTA > 50% to detect functional stenosis defined as invasive FFR ≦ 0.80 were 93.3% vs 73.3%, 73.9% vs 26.1%, 70.0% vs 39.3%, 94.4% vs 60.0%, and 81.6% vs 44.7%, respectively. For minimize 1-year cardiac events, the optimal cut-off value for more than 30% of disease prevalence was 0.80. However, the optimal cut-off value for 20, 25, and 30% was 0.54 in any cases. After the adjustment of CT-FFR using a formula of 0.3X + 0.634 for CT-FFR

Aim: Coronary computed tomography angiography (CCTA) findings of positive remodeling (index > 1.1) and low-attenuation plaque (< 30 Hounsfield units) are recognized as CT-verified high-risk plaque (CT-HRP). Therefore, we investigated the incremental prognostic value of evaluation of plaque characteristics using CCTA in asymptomatic patients. Methods: Overall, 495 consecutive patients without any known coronary artery disease who underwent CCTA were included in this study. Patients who underwent revascularization within 30 days of CCTA or had scans with poor image quality were excluded. Clinical follow-up data (716.5 ± 262.6 days) were available for 339 patients, who were analyzed for the current study. Framingham risk score (FRS), coronary artery calcium score (CACS), and CT-HRP were investigated as predictors of cardiac events by multivariable analysis using Cox proportional hazard model. Improvement of predictive accuracy by including CT findings was evaluated from reclassification [net reclassification indices (NRI) and integrated discrimination improvement (IDI)] standpoints. Results: During the follow-up period, 9 cardiac events (cardiac death: 0, nonfatal myocardial infarction: 2, hospitalization for unstable or progressive angina: 7) occurred. Multivariate Cox proportional hazard analysis demonstrated that CACS (HR, 13.23; 95% CI, 1.62–107.78, p < 0.0164) and CT-HRP (HR, 11.27; 95% CI, 1.24–102.12, p < 0.0321) were the independent predictors of cardiac events. NRI was 0.9556 (p < 0.0007) and IDI was 0.2582 (p < 0.0203), and the diagnostic performance improved by CT-HRP added to the combination of CACS and FRS. Conclusion: Although the cardiac event rate was low, the evaluation of CCTA plaque characteristics may provide incremental prognostic value to CACS in asymptomatic patients.

Key Clinical Message Polycythemia vera (PV) is a chronic myeloproliferative disease that is often complicated with thromboembolism. However, aortic stenosis (AS) could be a manifestation of the cardiovascular complications of PV possibly through shear stress and atherosclerosis. We report a rare case of rapidly progressed AS in a patient with PV.

A giant right coronary artery aneurysm (60 × 70 mm in size) was incidentally found by chest X-ray as an abnormal right atrial enlargement, and it needed surgical resection. Although the majority of giant coronary artery aneurysms present with symptoms of coronary ischemia, this case presented without any specific symptom. This study indicates that when chest X-ray shows abnormal atrial enlargement, a differential diagnosis of giant coronary artery aneurysm may need to be considered.

A 40-year-old man who was diagnosed with bronchial asthma and eosinophilia was transferred to our hospital due to a worsening respiratory status. He was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA), and eosinophilic pneumoniae. Cardiac magnetic resonance (CMR) imaging indicated Loffler endocarditis. Treatment was initiated using intravenous methylprednisolone, cyclophosphamide, and heparin as anticoagulation therapy. Three months later, CMR showed the improvement of the LV myocardium. In this case, the early diagnosis of Loffler endocarditis by CMR could prevent systemic embolism and CMR was useful for assessing the curative effects of steroid and immunosuppressant therapy.

A male individual aged 82 years with hypertension who had a smoking history, but no history of cardiovascular events, developed acute myocardial infarction immediately after he took oral polyethylene glycol electrolyte solution with ascorbic acid as a pretreatment for a colonoscopy to examine anemia. He took polyethylene glycol electrolyte solution with ascorbic acid at twice (2 L/h) the rate recommended in the package insert and by the physician. The patient showed impaired consciousness 2 h after taking polyethylene glycol electrolyte solution with ascorbic acid and his family called the emergency medical service. Upon arrival of the emergency medical service, his systolic blood pressure was 60 mmHg and heart rate was 50 bpm. Systolic blood pressure and impaired consciousness were slightly improved, but compensatory shock remained, at arrival at the emergency outpatient service at our hospital. No dyspnea or rash was apparent. The patient had no subjective chest pain; however, ST-segment elevation was detected in the electrocardiogram at II, III, aVF, V3R, and V4R. He was diagnosed with ST-segment elevation myocardial infarction and underwent a coronary catheter intervention for total occlusion of the right coronary artery. His shock state was abolished by this intervention. The patient was pretreated with polyethylene glycol electrolyte solution with ascorbic acid under close watch in the coronary care unit 4 days later, with no relapse of symptoms. Advanced cancer was found in the ileocecum by colonoscopy; consequently, the patient underwent a colectomy and was discharged from our hospital and transferred to another hospital for rehabilitation on hospital day 74. A Naranjo assessment score of 4 was obtained, indicating a possible relationship of acute myocardial infarction with misuse of the suspect drug, polyethylene glycol electrolyte solution with ascorbic acid.

Clinical demand for the prompt assessment of the activity of direct-acting factor Xa inhibitors in the emergency care setting is increasing. In the present study, we examined whether prothrombin time (PT) tests can serve as a clinically useful indicator of anti-factor Xa activity. In the first series, the in vitro effect of edoxaban on PT was evaluated by spiking human plasma with edoxaban and measuring PT using three different commercial PT tests. In the second series, the reversal effect of prothrombin complex concentrates (PCC) and activated PCC (aPCC) in edoxaban-spiked plasma was evaluated. In the third series, PT of plasma samples from patients administered either 15 or 30 mg/day of edoxaban was assessed, and the results were compared with edoxaban concentrations determined by a calibrated anti-factor Xa activity assay. The spike test revealed that all PT reagents positively correlated with edoxaban. The sensitivity to edoxaban varied among the three reagents and Triniclot(®) Excel S showed the best performance. Prolonged PT by edoxaban was reversed by PCC and aPCC in a dose-dependent manner; however, complete reversal was not achieved. Positive correlation between anti-factor Xa activity and PT was shown in the clinical samples at the edoxaban range from 0 to >300 ng/mL.

Aims Recent study suggests that algorithms such as the Duke Clinical score (DCS) may overestimate the pretest probability. The Agatston score representing the grade of coronary artery calcification can be simply calculated from low-radiation exposure ECG-gated plain CT. In this study, we investigated whether or not more superior diagnostic performance for obstructive coronary artery disease (CAD) can be obtained by combining DCS with the Agatston score. Methods and results Of 3939 consecutive patients suspected of having stable angina without known CAD who underwent Coronary Computed Tomography Angiography (CCTA) as well as calculation of the DCS and Agatston score at our hospital, 3688 patients were selected as subjects. Obstructive CAD was defined as >50% diameter stenosis on CCTA; we investigated the diagnostic performance based on the area under the curve (AUC) of a receiver operating characteristic (ROC) curve, Net Reclassification Improvement (NRI), and Integrated Discrimination Improvement (IDI). The AUCs of ROCs prepared using the DCS alone and combination of the DCS and Agatston score were 0.7137 and 0.8057, respectively, showing that the diagnostic performance of the combination was significantly superior to DCS alone ( P < 0.001). NRI was 0.8132 and IDI was 0.1374, showing that the diagnostic performance was improved by the combination of the DCS and Agatston score compared with DCS alone ( P < 0.001). NRI (0.3522) and IDI (0.0287) were improved compared with those of the Agatston score alone ( P < 0.001). Conclusion The combination of the DCS and Agatston score improved the diagnostic performance for obstructive CAD compared with DCS alone and Agatston score.

OBJECTIVE Proton magnetic resonance spectroscopy ((1)H-MRS) enables the clinician to noninvasively assess the amount of ectopic fat in the liver, skeletal muscle and myocardium. Recent studies have reported that the myocardial triglyceride (TG) content is associated with aging, metabolic disorders and cardiac dysfunction. However, the clinical usefulness of myocardial TG measurements in Japanese subjects has not been fully investigated. METHODS The myocardial TG content was evaluated using (1)H-MRS in 37 apparently healthy Japanese subjects, and the left ventricular function was measured on cardiac magnetic resonance imaging (MRI). Blood pressure, body composition and biochemical markers were measured in a fasting state, and cardiopulmonary exercise testing (CPX) was performed to evaluate exercise capacity. RESULTS The mean myocardial TG content was 0.85±0.40%. The myocardial TG content was significantly associated with the percent body fat (r=0.39), serum triglyceride level (r=0.40), estimated glomerular filtration rate (r=-0.37), anaerobic threshold (r=-0.36), maximal load of CPX (r=0.39), left ventricular end-diastolic volume (r=-0.41) and left ventricular end-systolic volume (LVESV) (r=-0.51) (all: p

The clinical significance of the transluminal attenuation gradient (TAG) has not been established. We evaluated the incremental diagnostic value of TAG by 320-row area detector computed tomography (320-ADCT). Subjects were 65 patients who underwent one-rotation scanning by 320-ADCT and invasive coronary angiography (ICA) within 3 months. TAG values were obtained for the major epicardial vessels 2 mm or more each in RCA, LAD and LCX using automatic analysis software. Moreover, TAG values that excluded calcified lesions in calculation of the regression line were also evaluated (excluded-TAG). In LAD, 21 intermediate lesions underwent functional flow reserve (FFR), and the incremental diagnostic value for functional stenosis was evaluated. The TAG values in the normal vessels were − 8.3 ± 5.0 (HU/cm) for the RCA (n = 32), − 23.3 ± 4.3 for the LAD (n = 9) and − 20.6 ± 10.0 for the LCX (n = 32). The RCA value was significantly higher (p

Radiation exposure remains a concern in the use of coronary CT angiography (CCTA). Full reconstruction (Full) and reconstruction using advanced patient motion correction (APMC) could obtain a lower radiation dose using low tube current scanning in a 320-row Area Detector CT (320-ADCT). The radiation dose for an imaging protocol using Full and APMC in daily practice was estimated. A total of 209 patients who underwent CCTA in 1 rotation scanning with 100 kv and adaptive iterative dose reduction 3D in 320-ADCT were enrolled. Imaging protocols were classified into 3 groups based on estimated slow filling time: (1) slow filling time ≥ 275 msec, Full with 30% of usual tube current (N = 43)(Full30%mA) (2) 206.3 msec ≤ slow filling time

A healthy teenage Japanese girl was admitted to our hospital after experiencing out-of-hospital cardiac arrest. She had attempted to commit suicide by taking 4,950 mg of disopyramide and 12 mg of flunitrazepam. Mechanical cardiopulmonary support was started with percutaneous cannulation of the femoral vessels. Several days later, a blood culture tested positive for Staphylococcus aureus. Transthoracic echocardiography showed a large mobile and solid mass attached to the apical part of the left ventricle. To the best of our knowledge, the anatomical location of a pedunculated mass originating from the apex is a rare condition.

Aim Very long chain saturated fatty acid (VLCFA) levels in erythrocytes are associated with metabolic syndrome (MS). However, the relationship between levels of the VLCFA ligonoceric acid (C24:0) in erythrocytes and the atherogenic lipoprotein profiles and inflammatory state in MS remain unclear. Methods Based on the International Diabetes Federation (IDF) definition of MS, 195 apparently healthy males were assigned to either an MS group (n = 38) or a non-MS group (n = 157). Fatty acid composition of erythrocytes was determined by gas liquid chromatography. Results Erythrocytes from the MS group had a significantly higher level of C24:0 than cells from the non-MS group (4.06 ± 0.48% versus 3.88 ± 0.34%; p = 0.03). C24:0 levels were significantly correlated with several components of MS. The C24:0 levels showed a significant negative correlation with LDL and HDL particle size. Multivariate linear regression analysis showed that C24:0 levels were independently correlated with LDL particle size after adjusting for age and each MS criterion. C24:0 levels were also positively correlated with log-transformed high-sensitivity CRP levels (p = 0.04). Conclusion C24:0 levels in erythrocytes are associated with specific atherogenic lipoprotein profiles and inflammation status in subjects with MS.

Cardiac amyloid light-chain amyloidosis (AL amyloidosis) is a rare disease with a very poor prognosis, associated with plasma cell dyscrasias such as monoclonal gammopathy of undetermined significance and multiple myeloma. Though bortezomib-containing regimens have achieved high hematologic response rates, there are still few reports describing the outcomes of Japanese patients. Six patients with severe cardiac AL amyloidosis were treated with bortezomib-containing regimens. Involved free light chain (iFLC) decreased immediately in most of these cases. However, the condition of heart failure and N-terminal pro-B-type natriuretic peptide (NT-proBNP) worsened in the early phase of this treatment and then improved several months later. At 29 months, the median duration of follow-up (2-47months), all patients remain alive except one who died of sudden cardiac arrest. Bortezomib-containing regimens are considered to be among the effective treatments for severe cardiac AL amyloidosis.

Background: Acute coronary syndrome (ACS) is an amplified state of inflammation and immune reaction. Dendritic cells (DCs) expressing various Toll-like receptors (TLRs) have been observed in atherosclerotic lesions, however, the clinical significance of DCs in pathogenesis of ACS has not been completely investigated. Methods: Ten patients with ACS and 10 patients with stable angina pectoris (SAP) were enrolled in this study. Monocyte-derived DCs were generated from CD14+ cells by culturing with granulocyte macrophage colony-stimulating factor and interleukin (IL)-4 for 6 days. Expression of cell surface CD86 and CD83 were measured by flowcytometry. Expression of genes, including CD86, CD83, CCL19, CCR7, TLR2, TLR4, TLR5, TLR8, and TLR9, were measured by real-time PCR. Plasma IL-6 and tumor necrosis factor (TNF)-α levels were also measured. Results: The number of CD86+CD83+DCs in the ACS group was significantly higher than that in the SAP group (P P P +CD83+ cells and plasma levels of IL-6 (P = 0.88, P +CD83+ cells TNF-α levels (r = 0.78, P < 0.0001). Conclusions: These results demonstrated that mono-cyte-derived DCs are activated in patients with ACS, suggesting that activated DCs may play an important role in the pathogenesis of ACS.

Background: Patients with arteriosclerosis obliterans (ASO) often have co-existing atherosclerotic diseases. The purpose of this study was to examine the clinical features of patients with ASO, including the overlap of atherosclerotic risk factors, characteristics of car-diovascular events, and clinical prognosis. Method: We enrolled 205 consecutive patients who had ankle brachial index (ABI) of ?0.9 between January 2008 and December 2009. Fontaine (F) classification and clinical background were evaluated and clinical events including mortality and major adverse cardiocerebro-vascular events (MACCEs) were determined. Results: There was a high prevalence of each risk factor. Sixty- five percent of subjects had three or more of the four overlapping risk factors, including hypertension, dia- betes, dyslipidemia, and smoking. After a maximum follow-up of 800 days, the incidence of MACCEs and mortality was 46% and 10%, respectively. We divided the patients into two groups according to the presence of ASO symptoms (F1 and F2-4) and compared the incidence of events. The incidence of MACCEs and mortality in the F2-4 group was significantly higher than that in the F1 group (P = 0.048, P = 0.044, respectively). After excluding lower extremity revascularization, coronary artery disease was a common cause of MACCEs, and the mortality rates after MACCEs increased in a stepwise manner according to F classification severity (P = 0.028). Conclusion: Patients with ASO had overlapping coronary risk factors and a high incidence rate of cardiovascular events. The incidence of coronary events was common, especially in symptomatic patients, and the mortality rates after MACCEs were high in accordance with F classification severity.

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a diagnostic biomarker for patients with congestive heart failure (CHF). However, the clinical significance of measurements of NT-proBNP levels in patients with coronary artery disease (CAD) who have undergone drug-eluting stent (DES) implantation has not been fully elucidated.We recruited 280 patients with documented CAD who were scheduled for elective coronary intervention and also age- and gender-matched 140 healthy subjects. Subjects with acute coronary syndrome, ongoing CHF, and stage IV or V chronic kidney disease were excluded. We measured the plasma NT-proBNP levels and followed the CAD patients who have undergone DES implantation for up to 62 months until occurrence of major adverse cardiovascular events (MACE). Plasma NT-proBNP levels were significantly higher in CAD patients compared to control subjects (p0.0001). In the CAD group, 25 patients developed MACE and the NT-proBNP levels in the MACE group were significantly higher compared to that in the non-MACE group (p=0.005). After adjusting for the confounding factors, high NT-proBNP levels were observed to be independent factors for CAD (p0.0001) and MACE (p=0.021).These results demonstrated that the measurements of NT-proBNP levels may be useful in identifying high-risk subjects among CAD patients who have undergone elective DES implantation.

Aim: We assessed levels of polyunsaturated fatty acid (PUFA) in serum and red blood cells (RBCs) among groups stratified by generation and its clinical significance in Japanese subjects living in an urban area.Methods: We enrolled 200 apparently healthy Japanese (126 males, mean age: 50.3±9.2 years) living in an urban area. Levels of PUFA, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and dihomo-gamma-linolenic acid (DGLA) in serum and RBCs were measured for each generation (G1

Background: Post-prandial hyperglycemia, hyperlipidemia, and endothelial dysfunction play an important role in the pathogenesis of atherosclerosis. Improvement in post-prandial hyperglycemia on α-glucosidase inhibitors (α-GIs) is associated with a risk reduction of cardiovascular diseases, but the post-prandial effects of α-GIs on endothelial function and incretin secretion in type 2 diabetic patients with coronary artery disease (CAD) remain unclear. Methods and Results: The post-prandial effects of a single administration of miglitol and voglibose on endothelial function and changing levels of glucose, insulin, lipids, glucagon-like peptide (GLP)-1, and gastric inhibitory polypeptide (GIP) were compared after a standard meal loading in 11 diabetic patients with CAD, using a placebo-controlled cross-over design. The changing levels of glucose, insulin and triglycerides at 60 min were significantly lower in the miglitol group than in the voglibose and placebo groups (all P

Aim: A sedentary lifestyle with insufficient exercise is associated with cardiovascular disease. Previous studies have demonstrated that endurance exercise benefits atherosclerosis and cardiovascular disorders; however, the mechanisms by which physical activity, such as voluntary exercise (Ex), produces these effects are not fully understood.Methods and Results: Eight-week-old male apolipoprotein (ApoE)-deficient mice were fed a standard diet (STD) or high fat diet (HFD) for 10 weeks. The HFD+Ex group mice performed Ex on a running wheel for 10 weeks. No significant differences in lipid profiles were observed between the HFD and HFD+Ex groups. Although changes in body and brown adipose tissue weights were comparable between the HFD and HFD+Ex groups, white adipose tissue weight was significantly lower in the HFD+Ex group than in the HFD group. The areas of atherosclerotic lesions in the aortic sinus and thoracoabdominal aorta were significantly reduced in the HFD+Ex group than in the HFD group (p

Proton magnetic resonance spectroscopy (1H-MRS) enables the assessment of myocardial triglyceride (TG) content, which is reported to be associated with cardiac dysfunction and morphology accompanied by metabolic disorder and cardiac hemodynamic status. The clinical usefulness of myocardial TG content measurements in patients with left ventricular hypertrophy (LVH) has not been fully investigated. We examined whether myocardial TG content assessed by 1H-MRS was useful for diagnosis in patients with LVH. To quantify myocardial TG content, we conducted 1H-MRS in 35 subjects with LVH. Left ventricular function was measured by cardiac magnetic resonance imaging. Patients were assigned to a hypertensive heart disease (HHD, n = 10) or hypertrophic cardiomyopathy (HCM, n = 25) group based on the histology and/or late gadolinium enhancement pattern. The myocardial TG content was significantly higher in the HHD group than in the HCM group (2.14 ± 1.29 vs. 1.09 ± 0.72 %, P

Background Cardiac events after revascularization are equally attributable to recurrence at site of culprit lesions and development of nonculprit lesions. We evaluated the hypothesis that coronary computed tomography ( CT ) angiography and coronary artery calcium score ( CACS ) performed before revascularization predicts cardiac events after treatment. Methods and Results Among 2238 consecutive patients without known coronary artery disease who underwent coronary CT angiography and CACS , 359 patients underwent revascularization within 30 days after CT ; in 337 of 359 (93.9%) follow‐up clinical information was available. In addition to known cardiac risk factors, CT findings were evaluated as predictors of cardiac events after revascularization: CACS and the presence of CT ‐verified high‐risk plaque ( CT ‐ HRP ). Improvement of predictive accuracy by including CT findings was evaluated from a discrimination (Harrell's C‐statistics) standpoint. During the follow‐up period (median: 673, interquartile range: 47 to 1529 days), a total of 98 cardiac events occurred. Cox proportional hazard model revealed that age, diabetes, triglyceride, CACS , and nonculprit CT ‐ HRP were significant predictors of overall cardiac events. Although not statistically significant, discriminatory power was greater for the model with CACS (C‐stat: 63.2%) and the model with both CACS and CT ‐ HRP (65.8%) compared to the model including neither CACS nor CT ‐ HRP (60.7%). Conclusions High CACS and the presence of nonculprit CT ‐ HRP performed before revascularization are significant predictors of cardiac events after revascularization.

Background The incremental prognostic value of the plaque features in coronary computed tomographic angiography (CTA) has not been well assessed. This study was designed to determine whether CTA high-risk plaques have prognostic value incremental to the Framingham risk score (FRS) and the severity of luminal obstruction. Methods A total of 628 newly symptomatic patients without known coronary artery disease underwent CTA. They were followed for a median of 677 days during which there were 26 cardiac events, including cardiac death, acute myocardial infarction, and hospitalization for unstable angina. Incremental prognostic value of adding plaque characteristics to the number of diseased vessels and the FRS was evaluated using 3 Cox models and net reclassification indexes. Results The discrimination index was significantly increased by adding the number of diseased vessels to the FRS (change in c-statistic from 65.8% to 78.6%, p = 0.028) but not significantly by further adding plaque characteristics (change in c-statistic from 78.6% to 80.0%, p = 0.812). However, improved model-fitting by adding plaque characteristics into the linear combination with risk score and the number of diseased vessels (p = 0.007 from likelihood ratio test) and the lowest value of Akaike's information criteria of that model indicated that plaque characteristics improved both predictive accuracy and discrimination perspective. More subjects reclassified by plaque characteristics were moved to directions consistent with their subsequent cardiac event status than in an inconsistent direction. Conclusions Evaluation of CTA plaque characteristics may provide incremental prognostic value to the number of diseased vessels and the FRS.

Aim: Circulating adiponectin comprises high, medium and low molecular weight (HMW, MMW, and LMW) forms. Decreased adiponectin levels have been demonstrated to correlate with the atherogenic lipoprotein profile in patients with metabolic syndrome(MS). However, the associations of these isoforms with the atherogenic lipoprotein profiles in the healthy population remain unclear. Methods: Apparently healthy male subjects were divided into non-MS(n=132) and MS(n=63) groups. We measured the total, HMW, MMW and LMW adiponectin levels by ELISA, and determined the detailed lipoprotein profiles by high-performance liquid chromatography. Results: The total and HMW adiponectin levels in the MS group were significantly lower than those in the non-MS group(3.8±1.9 vs. 4.9±2.4μg/mL, p＜0.001 and 1.6±1.2 vs. 2.5±1.9μg/mL, p＜0.001, respectively), whereas the MMW and LMW levels did not differ significantly between the groups. The total and HMW adiponectin levels correlated with the atherogenic lipoprotein profiles, including the following: 1) increased cholesterol levels in the small LDL subclasses; 2) decreased cholesterol levels in the larger HDL subclasses; 3) increased triglycerides(TGs) in almost all VLDL and LDL subclasses and 4) decreased TGs in the large HDL and increased TGs in the small HDL subclasses. In addition, a multivariate analysis demonstrated that the HMW adiponectin level was an independent predictor of the small LDL and HDL levels(p=0.02 for both). Conclusions: The HMW, but not MMW or LMW, adiponectin levels are associated with the typical atherogenic lipoprotein profiles, independent of MS components. Measurement of the HMW adiponectin levels could be useful for identifying the atherogenicity in apparently healthy males.

Aims Levels of saturated very long chain fatty acids (VLCFAs) are associated with coronary risk factors, including metabolic syndrome (MS), atherogenic lipoproteins, and systemic inflammation. However, the relationship between circulating levels of saturated VLCFA and coronary artery disease (CAD) remains unclear. Method We enrolled 100 consecutive CAD patients and 40 age-, gender-, and body mass index (BMI)-matched healthy control subjects. The levels of hexacosanoic acid (C26:0), a VLCFA, in whole blood were measured by gas–liquid chromatography mass spectrometry. Results C26:0 levels were significantly higher in the CAD group than in the control group (2.42 ± 0.32 vs. 2.27 ± 0.24 μg/ml, P = 0.01) and positively correlated with BMI ( r = 0.23, P = 0.008), triglyceride levels ( r = 0.22, P = 0.01), and hypertension ( P = 0.01). CAD patients with MS showed the highest C26:0 levels adjusted by hematocrit. Furthermore, adjusted C26:0 levels in CAD patients without MS were higher than those in controls ( P = 0.02), suggesting that C26:0 levels increased with the presence of CAD independent of MS. Our multivariate analysis revealed that high C26:0 levels in whole blood is an independent marker for CAD even after adjustment for age, gender, BMI, lipid profiles, fasting plasma glucose, and blood pressure. Conclusion High C26:0 levels in whole blood may be an independent marker for identifying the risks of CAD.

Ectopic fat accumulation plays important roles in various metabolic disorders and cardiovascular diseases. Recent studies reported that myocardial triglyceride (TG) content measured by proton magnetic resonance spectroscopy ((1)H-MRS) is associated with aging, diabetes mellitus, and cardiac dysfunction. However, myocardial TG content in athletes has not yet been investigated. We performed (1)H-MRS and cardiac magnetic resonance imaging in 10 male endurance athletes and 15 healthy male controls. Serum markers and other clinical parameters including arterial stiffness were measured. Cardiopulmonary exercise testing was also performed. There were no significant differences in clinical characteristics including age, anthropometric parameters, blood test results, or arterial stiffness between the two groups. Peak oxygen uptakes, end-diastolic volume (EDV), end-systolic volume (ESV), left ventricular (LV) mass, peak ejection rates and peak filling rates were significantly higher in the athlete group than in the control group (all P