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Fraction flow reserve (FFR) derived from computed tomography (FFRCT) has been proposed to be an effective gatekeeper for invasive angiographic referral. The purpose of the present study is to examine the real-world diagnostic performance of FFRCT and myocardial perfusion imaging as well as to assess the utility of FFRCT as a gatekeeper for invasive coronary angiography in patients suspected of having obstructive coronary artery disease. Total of 146 consecutive patients underwent both single-photon emission computed tomography (SPECT) and invasive FFR were evaluated. An FFRCT value 1 to 2 cm distal to a stenosis ≤0.80 was defined as positive for ischemia and a summed stress score ≥2 or transient ischemic dilatation ≥1.2 were positive for ischemia with the invasive FFR value of

Statins are widely used medications for the treatment of hypercholesterolemia, as well as prevention of cardiovascular disease. We report two patients with type 1 diabetes who developed autoimmune hepatitis after the administration of statin. The first patient developed the marked elevation of liver enzymes 6 months into atorvastatin therapy. The second patient developed liver dysfunction 8 months after the initiation of rosuvastatin therapy. Liver biopsies in both patients showed either portal, interface and lobular hepatitis or a piece‐meal necrosis with lymphocytes and plasma cell infiltration that were compatible with autoimmune hepatitis. Then, both patients were started on prednisolone, to which they responded well. Liver biopsy is to be considered for type 1 diabetes patients if there is no improvement of liver dysfunction after discontinuation of statins., Statins are a widely used drug for the treatment of hypercholesterolemia, as well as prevention of the onset of cardiovascular disease. We report two patients with type 1 diabetes who developed autoimmune hepatitis after the administration of statin.

Aims Lipoprotein(a) [Lp(a)] is a plasma lipoprotein consisting of a low-density lipoprotein (LDL)-like particle with apolipoprotein (Apo)(a), attached via a disulfide bond to Apo B100. Previous studies have shown that high Lp(a) levels are associated with an increased risk of cardiovascular disease in patients with familial hypercholesterolemia (FH). To date, limited data are available as to distribution of Lp(a) in FH and associations of Lp(a) with other lipid profiles and cardiovascular disease. Our study aimed to investigate serum Lp(a) levels in relation to other lipid profiles and clinical conditions in the national largest-ever cohort of Japanese FH patients. Methods This study is a secondary analysis of the Familial Hypercholesterolemia Expert Forum (FAME) Study that includes a Japanese nationwide cohort of FH patients. In 399 patients under treatment for heterozygous FH who had a baseline measurement of serum Lp(a), the present study examined the distribution of Lp(a) levels and associations of Lp(a) with other lipid profiles and clinical conditions including coronary artery disease (CAD). Results The distribution of Lp(a) was skewed to the right with a median of 20.8 mg/dL, showing a log-normal distribution. Serum Apo B and Apo E levels were positively associated with Lp(a) levels. Age-adjusted mean of Apo B was 8.77 mg/dL higher and that of Apo E was 0.39 mg/dL higher in the highest category (40+ mg/dL) of Lp(a) than in the lowest category (＜20 mg/dL). LDL-C levels did not show such an association with Lp(a) levels. A tendency towards a positive relationship between Lp(a) and prevalent CAD was observed in men. Conclusion Our study demonstrated a distribution pattern of Lp(a) in Japanese FH patients and positive relationships of Lp(a) with Apo B and Apo E levels.

AIMS: Relationship between baseline eGFR and the rate of decline in eGFR was investigated in diabetic kidney disease. MATERIALS AND METHODS: Patients with type 2 diabetes with microalbuminuria (MI) (n = 124) or macroalbuminuria (MA) (n = 81) received team-based medical care to prevent the development of diabetic kidney disease. The decline in eGFR over 4 years, divided into the first year and subsequent 3 years, was estimated by linear-mixed modeling. RESULTS: The eGFR showed a rapid decline during the first year, followed by a slower decline. On multiple regression analysis, the baseline eGFR was positively correlated with HbA1c in MI and negatively correlated with carotid plaque in MI and in MA. Subsequent eGFR decline following 1-year intervention was negatively correlated with the baseline eGFR and HbA1c level at 1 year in MI, whereas it was positively correlated with baseline eGFR and negatively correlated with the amount of proteinuria at 1 year in MA. Even in maintained baseline eGFR(≧ 60 ml/min/1.73 m(2)) at the first year, when HbA1c ≧ 7.5%, eGFR reduction rate and years to ESKD were much faster and shorter, compared to the group of HbA1c

Aims Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein (LDL) cholesterol levels, xanthomas including Achilles tendon thickening, and premature coronary artery disease (CAD). Carotid intima-media thickness (IMT) is a well-established surrogate marker for CAD in FH and Achilles tendon thickening is a specific physical finding in patients with FH. The objective of the present study was to identify factors associated with carotid IMT and Achilles tendon thickness in FH heterozygotes on lipid-lowering therapy. This study also aimed to examine the follow-up changes in carotid IMT and Achilles tendon thickness among them in the current real-world FH practice. Methods The current study is a subanalysis of the Familial Hypercholesterolemia Expert Forum (FAME) Study. The severity of carotid atherosclerosis was assessed with the maximal and mean IMT using ultrasonography, and Achilles tendon thickness was measured using X-rays. The present study used 571 patients under medical treatment for heterozygous FH who had baseline measurements for maximal IMT (n=511), mean IMT (n=459), or Achilles tendon thickness (n=486). The IMT was measured annually, and Achilles tendon thickness was evaluated every two years. Results Higher LDL cholesterol (LDL-C) level and lower HDL cholesterol (HDL-C) level were associated with greater maximal and mean IMT as well as greater Achilles tendon thickness. Achilles tendon thickness tended to be greater in patients who had a smoking history than in never-smokers. Maximal IMT and Achilles tendon thickness were significantly greater in patients with CAD than in those without. Additionally, lower HDL-C level and hypertension were associated with higher values of maximal and mean IMT, suggesting the importance of comprehensive risk management including reduced HDL-C and blood pressure control in FH care. In longitudinal observations, percentage changes in maximal IMT and mean IMT gradually increased during the observation period. In contrast, percentage changes in Achilles tendon thickness became progressively thinner throughout the observation period. Conclusions We found a positive association between LDL-C levels and severity of carotid atherosclerosis in heterozygous FH patients on treatment. This observation suggests the insufficiency of lipid-lowering therapy and the presence of therapeutic inertia among clinicians in the real-world FH practice.

Aims Familial hypercholesterolemia (FH) is a genetic disorder characterized by high serum levels of low-density lipoprotein (LDL)-cholesterol (LDL-C), tendon and skin xanthomas, and premature coronary artery disease (CAD). In Japan, detailed information on the current status of drug therapies for patients with FH has not been reported so far, and their efficacy and safety have not been clarified. After the introduction of ezetimibe, which can further reduce serum LDL-C levels on top of statins, the changes of management for FH patients with these drugs are of particular interest. The current study aimed to evaluate the clinical status of FH heterozygotes and homozygotes, especially focusing on the real-world lipid-lowering drug therapy, attained serum LDL-C levels, and cardiovascular events at registration and during the follow-up. Methods The FAME Study enrolled 762 heterozygous (including 17 newly diagnosed cases) and 7 homozygous FH patients from hospitals and clinics nationwide. Diagnosis of FH was based upon the criteria defined in the Study Report in 2008 of the Research Committee on Primary Hyperlipidemia supported by Grants-in-Aid for Scientific Research from the Japanese Ministry of Health, Labor and Welfare. Data analysis was primarily carried on heterozygous FH patients. Results Xanthoma or thickening of the Achilles tendon was observed in more than 80% of the patients. CAD was recorded in 23% of patients. Patients with parental and sibling CAD accounted for 47% and 24%, respectively. At baseline, patients without CAD who had LDL-C ＜100 mg/dL accounted for 12.3% and those with CAD who had attained the target (LDL-C ＜70 mg/dL) in the secondary prevention accounted for only 1.8%. In the multiple logistic analysis, male sex, age ＞40, heterozygous FH score ＞20, hypertension, and sibling CAD were significantly and positively associated with prevalent CAD, whereas serum HDL-cholesterol levels showed a significant inverse association with CAD. Patients treated with statin alone, statin＋ezetimibe, statin＋resin, or statin＋probucol accounted for 31.1%, 26.3%, 4.0%, and 3.7%, respectively. Patients treated with three-drug combination (statin＋ezetimibe＋resin or statin＋ezetimibe＋probucol) accounted for 7.5%. Statins and ezetimibe were used in 88.0% and 48.0% at the baseline, respectively. Although high-intensity statins were mainly prescribed, statin doses were much lower than those reported in Western countries. The addition of ezetimibe resulted in ~20% reduction in serum LDL-C. CAD was diagnosed in 17 patients with 21 episodes during follow-up. The Cox hazard model analysis demonstrated that male sex, CAD at the baseline, and parental CAD were related to the development of atherosclerotic cardiovascular disease (ASCVD) events. Furthermore, an increase in serum HDL-C was associated with a significant reduction of ASCVD events, while serum LDL-C and triglyceride levels were not related to ASCVD events. Conclusion The prevalence of CAD in Japanese patients with heterozygous FH is still very high. In most of the cases, the target level of serum LDL-C was not achieved for primary and secondary prevention of CAD, suggesting that a more aggressive LDL-C lowering and appropriate management of residual risks are necessary.

To compare the diagnostic performance of on-site workstation-based computed tomography-derived fractional flow reserve (CT-FFR)Few data of CT-FFR were reported regarding the diagnostic performance for detecting hemodynamically significant coronary artery disease (CAD). This retrospective single-center analysis included 132 vessels in 77 patients who underwent CT angiography, myocardial perfusion imaging (MPI), and invasive FFR. The correlation coefficient between CT-FFR and invasive FFR and optimal cut-off value for CT-FFR to identify invasive FFR ≤ 0.8 were evaluated. The diagnostic accuracies of CT- FFR, and MPI were evaluated using an area under the receiver-operating characteristic curve (AUC) with invasive FFR as a reference standard. Diagnostic performance of CT-FFR was also evaluated concerning lesion characteristics, including intermediate lesions, left main lesions, tandem lesions, and/or diffuse lesions, and coronary calcium (Agatston score over 400). The Receiver Operating Characteristic curve analysis showed that the optimal cut-off value of CT-FFR for detecting invasive FFR ≤ 0.80 was 0.80 [AUC = 0.83, 95%CI: 0.76–0.90). Diagnostic sensitivity, specificity, positive and negative predictive value, and accuracy of CT-FFR when compared with those of MPI regarding per-patient analysis were 93% vs. 63%, 48% vs. 61%, 81% vs. 79%, 73% vs. 41%, and 79% vs. 62%, respectively, and for per-vessel analysis were 89% vs. 24%, 66% vs. 82%, 75% vs. 61%, 83% vs. 48%, and 78% vs. 51%, respectively. The AUC of the CT-FFR was significantly higher than MPI (0.83 vs. 0.57, p

This study aimed to characterize diabetic patients incidentally found to be positive for glutamic acid decarboxylase autoantibodies (GADA) in general practice. Using bridging‐type enzyme‐linked immunosorbent assay, we screened 1,040 patients with phenotypic type 2 diabetes for GADA, finding 25 (2.4%) to be positive. However, on retesting, with a median interval of 19 days, 44% of GADA‐positive patients turned negative (Disappearing Group). The mean age at diabetes onset was significantly higher (P, Using bridging‐type enzyme‐linked immunosorbent assay, we screened 1,040 patients with clinically diagnosed type 2 diabetes for glutamic acid decarboxylase autoantibodies (GADA) , finding 25 (2.4%) to be positive. However, on retesting, with a median interval of 19 days, 44% of the GADA‐positive patients turned negative. We also found that all patients whose GADA disappeared immediately had GADA titers of

Aims/Introduction The usefulness of markers of carotid plaque, such as sum (PS) and maximum (P-max) of the plaque thickness, in combination with intima-media thickness in the common carotid artery (CIMT) for the detection of obstructive coronary artery disease (CAD) was investigated in patients with type 2 diabetes without known CAD. Materials and Methods B-mode ultrasonographic scanning of the carotid artery and multislice computed tomography coronary angiography were carried out in 332 asymptomatic patients with type 2 diabetes. Results For the presence of obstructive CAD when incorporating PS or P-max to standard risk factors in a multiple logistic regression model, the classification ability in PS and P-max increased greatly (area under the curve [AUC] 0.827 vs 0.720 [net reclassification index {NRI} = 0.652, P

Background Coronary high-intensity plaques detected by noncontrast T1-weighted imaging may represent plaque instability. High-intensity plaques can be quantitatively assessed by a plaque-to-myocardium signal-intensity ratio (PMR). Objectives This pilot, hypothesis-generating study sought to investigate whether intensive statin therapy would lower PMR. Methods Prospective serial noncontrast T1-weighted magnetic resonance imaging and computed tomography angiography were performed in 48 patients with coronary artery disease at baseline and after 12 months of intensive pitavastatin treatment with a target low-density lipoprotein cholesterol level Results In the statin group, 12 months of statin therapy significantly improved low-density lipoprotein cholesterol levels (125 to 70 mg/dl; p Conclusions Statin treatment significantly reduced the PMR of high-intensity plaques. Noncontrast T1-weighted magnetic resonance imaging could become a useful technique for repeated quantitative assessment of plaque composition. (Attempts at Plaque Vulnerability Quantification with Magnetic Resonance Imaging Using Noncontrast T1-weighted Technique [AQUAMARINE]; UMIN000003567 )

ObjectivesThe aim of this study was to determine whether coronary high-intensity plaques (HIPs) visualized by noncontrast T1-weighted imaging can predict future coronary events.BackgroundCoronary HIPs are associated with characteristics of vulnerable plaques, including positive remodeling, lower Hounsfield units, and ultrasound attenuation. However, it remains unclear whether the presence of HIPs is associated with increased risk for coronary events.MethodsThe signal intensity of coronary plaques was prospectively examined in 568 patients with suspected or known coronary artery disease (CAD) who underwent noncontrast T1-weighted imaging to determine the plaque-to-myocardium signal intensity ratio (PMR).ResultsDuring the follow-up period (median 55 months), coronary events were observed in 55 patients. Receiver-operating characteristic curve analysis identified a PMR of 1.4 as the optimal cutoff for predicting prognosis. Multivariate Cox regression analysis identified the presence of plaques with PMRs ≥1.4 as the significant independent predictor of coronary events (hazard ratio: 3.96; 95% confidence interval: 1.92 to 8.17; p < 0.001) compared with the presence of CAD (hazard ratio: 3.56; 95% confidence interval: 1.76 to 7.20; p < 0.001) and other traditional risk factors. Among the 4 groups based on PMR cutoff and the presence of CAD, coronary event–free survival was lowest in the group with PMRs ≥1.4 and CAD and highest in the group with PMRs

Background Glucagon-like peptide 1 analogs are expected to exert a cardio-protective action due to their effective glucose-lowering action and favorable potency on multifactorial metabolic pathways. However, the safety and tolerability of liraglutide treatment after a recent acute coronary syndrome (ACS) in Japanese patients with type 2 diabetes mellitus (T2DM) have yet to be fully established. Methods A total of eight T2DM patients were recruited within 2 weeks after the onset of a ST-elevation myocardial infarction (STEMI) followed by successful percutaneous coronary intervention (PCI). The patients continued to receive liraglutide (up to 0.9 mg once daily) for 24 weeks after the ACS combined with standard treatment such as a statin or beta-blocker. Changes in various metabolic parameters from pre-liraglutide treatment values were evaluated 24 weeks after liraglutide treatment, and included glycemic and lipid profiles, and cardiac systolic and diastolic function assessed by cardiac ultrasonography. Results Twenty-four weeks of treatment with liraglutide reduced body weight (67.0 ± 5.8 kg to 62.0 ± 7.8 kg, p = 0.003) and HbA1c level (6.6 ± 0.5% to 5.9 ± 0.5%, p = 0.006) and increased the level of 1,5-anhydroglucitol (12.8 ± 6.9 μg/mL to 18.7 ± 8.2 μg/mL, p = 0.008) without development of hypoglycemia. There were no significant changes over 24 weeks in left ventricular systolic or diastolic function assessed by cardiac ultrasonography. No participant developed a major adverse cardiac event during the 24 weeks of liraglutide treatment, defined as cardiac death, new onset or recurrence of myocardial infarction, or needing target lesion revascularization. Conclusions The present trial demonstrated that liraglutide treatment after onset of STEMI was well-tolerated in Japanese patients with T2DM over 24 weeks, and provided the first evidence to support clinical application of liraglutide treatment even just after ACS in Japanese high-risk T2DM patients.

The usefulness of the sum of plaque thickness in the carotid artery (plaque score; PS), as a prediction of coronary artery disease (CAD) was investigated in patients with type 2 diabetes mellitus.B mode ultrasonographic scanning of the carotid artery and multislice computed tomography (MSCT) coronary angiography were performed in 227 diabetic patients without known cardiac disease.The PS was useful to predict the presence of diseased [nonobstructive and obstructive] CAD (≧3 segments) and obstructive (≧50%) CAD with cut-off value of 3.5mm (area under curve: 0.745 and 0.782, respectively), according to a receiver operating characteristics curve analysis. A multivariate logistic analysis of baseline risk factors showed that the PS was independent risk factor for the prediction of diseased and obstructive coronary artery disease (R(2)=0.2165, p0.0001 and R(2)=0.2265, p0.0001, respectively). The PS was most significant predictor of the number of diseased and obstructive segments of the coronary artery in a multiple regression analysis (R(2)=0.2022, p0.0001 and R(2)=0.2209, p0.0001, respectively).The PS in the carotid artery was useful for the prediction of the presence and the extent of CAD, and was most important as a screening test for the identification of a high risk group of asymptomatic diabetic patients.

Objective:To examine the long-term outcome of the stent fracture (SF) and the potential predictive factors contributing to in-stent restenosis (ISR) in the fractured stent. Background:The SF is thought to be a higher risk of ISR in drug-eluting stent, although SF does not always develop ISR. Methods:The consecutive 1,228 de novo lesions in 1,079 patients who underwent sirolimus-eluting stents implantation and assessed by 8 months follow-up coronary angiography were retrospectively analyzed. Results:One hundred and seventeen SFs (9.5%) were identified in 100 patients and 22 (18.8%) SFs revealed ISR at the first follow-up. In addition, 16 (13.7%) developed new ISRs from 95 residual SFs without ISR prior to the second follow-up. Overall, 38 (32.5%) of all 117 SFs developed ISR, and 16 (42.1%) of 38 SFs occurred in a late phase beyond the first 8 months follow-up. A higher risk of ISR in the SF site was associated with the chronic total occlusion (ISR vs. no ISR: 34.2% vs. 16.5%, P = 0.0304), calcified lesions (55.3% vs. 34.2%, P = 0.0299), and correspondence 89.5% versus 43.0%, P < 0.0001 (SF site occurring at the original target lesion site) in the univariate analysis. The correspondence was identified as the only strong predictive factor for ISR at the SF site according to a multivariate logistic regression analysis (odds ratio 12.6, 95% confidence interval 3.82–53.5, P < 0.0001). Conclusions:SF occurring at the site of the original target lesion was a strong independent predictor of ISR. This indicates the need for a careful, long-term follow-up in those situations, even when no significant ISR is initially detected. (J Interven Cardiol 2011;24:165–171)

Objectives This study sought to characterize coronary hyperintense plaques (HIP) using noncontrast T1-weighted imaging (T1WI) in cardiac magnetic resonance, which was then compared with multislice computed tomography and intravascular ultrasound. Background Carotid plaque components such as intraplaque hemorrhages and/or lipid-rich necrotic cores can be detected as HIP by noncontrast T1WI. Although coronary HIPs have been successfully detected using this technique, the properties of hyperintense signals in coronary plaques have not yet been systematically evaluated. Methods Thirty-eight lesions from 37 patients with angina pectoris who demonstrated >70% coronary stenosis on multislice computed tomography were evaluated by noncontrast T1WI using a 1.5-T magnetic resonance imager, and 25 lesions were evaluated by intravascular ultrasound. Signal intensity of coronary plaque to cardiac muscle ratio >1.0 was defined as HIP. We divided 25 lesions into the 2 groups, according to the presence or absence of HIP: HIP (n = 18) and non-HIP (n = 7) groups. Results In comparison with the non-HIP group, the HIP group demonstrated significantly higher coronary plaque to cardiac muscle ratio (1.7 ± 0.7 vs. 0.9 ± 0.1, p Conclusions The typical HIP case was associated with ultrasound attenuation, positive remodeling, remarkably low computed tomography density, and a high incidence of slow-flow phenomena. Noncontrast T1WI in cardiac magnetic resonance imaging may be useful for the assessment of coronary plaque characterization in patients with coronary artery disease.

We report on the most recent data confirming the angiographic and pathological efficacy of LDL-apheresis for coronary atherosclerosis of a familial hy percholes-terolemia (FH) patient using collected data of a large number of cases and especially of one autopsy case, Changes in coronary artery stenosis have been assessed angio-graphically in 37 FH patients in the LDL-Apheresis Regression Study (LARS) group of 13 institutions in Japan. Definite regression was observed in 21 segments by visual and computer analysis. Fourteen of 37 patients (37.8%) who had received LDL-apheresis treatment in combination with cholesterol-lowering drugs had at least one regressed segment without any progressed segment. We pathologically examined at autopsy the coronary arteries in one FH patient who had received long-term LDL-apheresis therapy before death. The results revealed the process of scarring of atheromatous plaque, suggesting pathological regression correlated with the angiographic regression shown in serial angiograms taken during LDL-apheresis treatment. It was further suggested that the formation of an eccentric thickened wall lesion rich in collagen fiber prevented atheromatous plaque from tearing off. Such tearing off might lead to an acute coronary event. Aggressive cholesterol-lowering therapy based on LDL-apheresis can induce both angiographic and pathological regression in coronary atherosclerosis of FH patients.

Background: The efficacy of lanthanum carbonate as a phosphate binder for the treatment of hyperphosphatemia has been reported, but not from a double-blind, comparator-controlled comparative study. Methods: The safety and efficacy of lanthanum carbonate and calcium carbonate on serum phosphate and calcium levels in Japanese hemodialysis patients were assessed by a randomized, double-blind, comparator-controlled, parallel group, multicenter study. This study is the first study using a randomized, double-blind method to compare lanthanum carbonate and calcium carbonate as phosphate binders. Results: In the double-blind phase, the changes in the scrum phosphate level were similar in the lanthanum carbonate and calcium carbonate groups. The differences in the corrected serum calcium level or the calcium x phosphate products between the 2 groups were not statistically significant. However, the mean change in the corrected serum calcium level from baseline to the last outpatient visit was significantly lower in the lanthanum carbonate group than in the calcium carbonate group. The incidence of hypercalcemia in the lanthanum carbonate group was also significantly lower than in the calcium carbonate group. Conclusion: Both compounds show similar efficacy on the serum phosphate level in patients undergoing hemodialysis when the dose is managed in a dose-variable and double-blind manner. However, lanthanum carbonate is superior in terms of lowering the incidence of hypercalcemia.

Although some studies have reported favorable effects of direct hemoperfusion with polymyxin-B-immobilized fiber columns (PMX) for the treatment of septic shock, few studies have demonstrated the efficacy of PMX in studies with a uniform case definition and without any other blood purification techniques.Fifty-two patients with severe sepsis or septic shock secondary to colorectal perforation were treated with PMX. Hemodynamic alterations and plasma concentrations of endotoxin, interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1Ra), IL-6, IL-8, and IL-10 were evaluated following PMX treatment.We observed a significant reduction in plasma endotoxin in the nonsurvivors immediately after PMX treatment compared to before treatment. Systolic blood pressure was markedly increased and circulating levels of IL-1beta, IL-1Ra, and IL-8 were significantly reduced during a 2-h interval of PMX.Our findings suggested that PMX treatment appears to adsorb endotoxin and also modulates circulating cytokine during a 2-h interval of direct hemoperfusion in septic patients with such condition.

The aim of this study was to investigate whether thoracic aorta calcification (TAC) on computed tomography (CT) and coronary risk factors had any correlation with obstructive coronary artery disease (CAD) on angiography. A total of 225 consecutive Japanese patients underwent both thoracic conventional helical CT and coronary angiography. The thoracic aorta was divided into 4 locations according to the aortic anatomy (inner curve of the aortic arch, aortic arch but not on the inner curve, ascending aorta, and thoracic descending aorta). The classified TAC and coronary risk factors were evaluated for the presence or absence of obstructive CAD. TAC was detected in 185 patients; 141 of 225 patients had significant obstructive CAD. All of the 13 patients with no TAC and no coronary risk factors had no CAD. The obstructive CAD rate with 1 thoracic calcified location and with no, 1, or 2 coronary risk factors was 10%, 58%, and 90%, respectively, and each showed a significant difference (p < 0.0001). The combinations of TAC and coronary risk factors with obstructive CAD were 1 or 2 thoracic calcified locations with 3 coronary risk factors, and 3 thoracic calcified locations with more than 2 coronary risk factors. Increasing thoracic calcified locations and increasing coronary risk factors indicated a higher likelihood of CAD.

The polymyxin B immobilized fiber column (PMX) has been used to treat septic shock patients since 1994 under the Japanese health insurance system. In 1997, the results of the first multicenter clinical study enrolling 42 patients were published, showing a significant reduction in the plasma endotoxin level of the survivors, whilst there was no change with the non-survivors, following treatment with PMX. Body temperature, blood pressure and hemodynamic abnormalities were significantly improved after PMX treatment. The second multicenter study enrolling 88 patients demonstrated that in the survivors, the plasma level of mediators such as TNF-α, IL-6, IL-10 and plasminogen activator inhibitor-1 (PAI-1) was significantly decreased following treatment with PMX. Recent studies investigating the mechanisms of PMX treatment have indicated that various mediators other than endotoxin might be adsorbed by PMX. Possible mediators include endogenous cannabinoids, such as macrophage-derived anandamide, and platelet-derived 2-arachidonyl glyceride (2-AG) and tetrahydrobiopterin (BH4), an essential cofactor for inducible NO synthase. The interaction between PMX and activated monocytes may suggest an alternative mechanism for the improvement in patient condition following PMX treatment. Further studies are needed to clarify the mechanisms of PMX treatment and to strengthen the scientific basis of this treatment.

Coronary high-intensity plaques detected by noncontrast T1-weighted imaging may represent plaque instability. High-intensity plaques can be quantitatively assessed by a plaque-to-myocardium signal-intensity ratio (PMR).This pilot, hypothesis-generating study sought to investigate whether intensive statin therapy would lower PMR.Prospective serial noncontrast T1-weighted magnetic resonance imaging and computed tomography angiography were performed in 48 patients with coronary artery disease at baseline and after 12 months of intensive pitavastatin treatment with a target low-density lipoprotein cholesterol level 80 mg/dl. The control group consisted of coronary artery disease patients not treated with statins that were matched by propensity scoring (n = 48). The primary endpoint was the 12-month change in PMR. Changes in computed tomography angiography parameters and high-sensitivity C-reactive protein levels were analyzed.In the statin group, 12 months of statin therapy significantly improved low-density lipoprotein cholesterol levels (125 to 70 mg/dl; p 0.001), PMR (1.38 to 1.11, an 18.9% reduction; p 0.001), low-attenuation plaque volume, and the percentage of total atheroma volume on computed tomography. In the control group, the PMR increased significantly (from 1.22 to 1.49, a 19.2% increase; p 0.001). Changes in PMR were correlated with changes in low-density lipoprotein cholesterol (r = 0.533; p 0.001), high-sensitivity C-reactive protein (r = 0.347; p 0.001), percentage of atheroma volume (r = 0.477; p 0.001), and percentage of low-attenuation plaque volume (r = 0.416; p 0.001).Statin treatment significantly reduced the PMR of high-intensity plaques. Noncontrast T1-weighted magnetic resonance imaging could become a useful technique for repeated quantitative assessment of plaque composition. (Attempts at Plaque Vulnerability Quantification with Magnetic Resonance Imaging Using Noncontrast T1-weighted Technique [AQUAMARINE]; UMIN000003567).

But: Evaluer le rapport entre les parametres cliniques et plasmatiques et les modifications d'activite d'endotoxines plasmatiques, d'une part, et l'utilisation de polymyxin B (PMX, Toray Medical Co., Ltd., Tokyo, Japon), un absorbant d'endotoxine, pendant 2 heures, d'autre part. Patients et methodes: Au total, 88 patients consecutifs, admis pour traitement d'un sepsis severe ou une defaillance viscerale par PMX. Pendant le traitement, la reanimation etait sans particularite. On a mesure, avant, immediatement et 24 h apres l'administration de PMX, les facteurs endotoxine et tumor necrosis factor (TNF)-alpha, l'interleukine (IL)-6, IL-10, les activites du plasminogen activator inhibitor-1 (PAI-1), et certains autres parametres cliniques. Resultats: Les scores moyens APACHE II et III ont ete, respectivement, de 24,2 ± 1,0 et de 85,8 ± 3,0. La survie a deux semaines a ete de 51,1%. Les activites du TNF-alpha, d'IL-6, d'IL-10 et de PAI-1 ont ete significativement reduites chez les survivants pendant le traitement par PMX et/ou le jour apres. Chez les non survivants, aucune modification significative n'a ete notee pour ces parametres sauf en ce qui concerne le TNF-alpha. Dans le sous-groupe de patients ou l'endotoxine plasmatique a diminue de plus de 30%, on a remarque une diminution significative de l'IL-6, du TNF-alpha et du PAI-1 apres 2 h et/ou le jour d'apres, mais aucun de ces quatre parametres n'a change chez les non-survivants. Conclusion: Le PMX, pendant les deux heures du traitement, contribue a absorber des endotoxines du plasma et reduit le taux de cytokines inflammatoires, ameliorant les parametres cliniques.

Long-term low density lipoprotein (LDL) apheresis using dextran sulfate cellulose (DSC) columns is a well tolerated treatment for drug refractory hypercholesterolemia with coronary heart disease (CHD). Hypercholesterolemic patients may benefit from LDL apheresis combined with cholesterol lowering drug therapy in terms of the prevention of the progression of atherosclerosis, stabilization of atheromatous plaque, and reduction of cardiac events. The major adverse reaction of LDL apheresis is temporal hypotension caused by hypovolemia or vasovagal reactions due to extracorporeal circulation. Anaphylactoid reactions in patients administered angiotensin converting enzyme inhibitors (ACE-I) are other dextran sulfate cellulose column related adverse reactions, which must be carefully prevented by ceasing the administration of ACE-I before LDL apheresis treatment. ACE-I must not be administered to patients undergoing LDL apheresis.

In this case report, we describe a rare patient who experienced complete fracture of a sirolimus-eluting stent that was implanted for a focally calcified lesion of the right coronary artery ostium. Although the fractured fragment migrated somewhere in the systemic circulation, fortunately there were no complications. Implantation for ostial lesions of the right coronary artery should be performed with great care.

This paper reports the results of the laser long-path absorption experiments carried out with the Retroreflector in Space (RIS) on the Advanced Earth Observing Satellite (ADEOS). The RIS is a 0.5 m diameter single-element hollow retroreflector with a unique optical design which uses a curved mirror surface to correct velocity aberrations caused by the satellite movement. In the RIS experiments a laser beam was transmitted from a ground station, reflected by the RIS, and received back at the ground station. The absorption of the intervening atmosphere was measured in the round-trip optical path. After the launch of the ADEOS in August 1996, the optical characteristics of the RIS were tested, and it was confirmed that the RIS worked well in orbit. The spectroscopic measurement was carried out with the single-longitudinal-mode TEA lasers by means of the method utilizing the Doppler shift of the reflected beam caused by the movement of the satellite. The spectrum of ozone was successfully measured in the region, and the measurement of the column contents of ozone was validated with the simultaneous heterodyne spectrometer measurement. In June 1997, however, the experiment with the RIS was discontinued due to the malfunction of the ADEOS solar paddle.

The long-term effects of low-density lipoprotein (LDL) apheresis (LA) on the progression and regression of atherosclerosis were evaluated by angiographic and pathological findings as well as ultrasonography based studies, and the clinical significance of the treatment was evaluated. We studied 11 patients with familial hypercholesterolemia (FH), 2 with homozygous FH and 9 with severe heterozygous FH who received combined LA and drug therapy for a mean of 7.7 years. During the treatment period, the mean time-averaged level of LDL cholesterol was 181+/-52 mg/dl. According to the coronary angiographic results, 3 patients showed regression, 6 patients showed progression, and 2 patients showed no change. Cardiac events occurred in 6 patients. We pathologically examined at autopsy the coronary arteries of 1 FH patient who had received long-term LA therapy before death. The results revealed the process of scarring of atheromatous plaque, suggesting pathological regression correlated with the angiographic regression shown in serial angiograms taken during LA treatment. It was further suggested that the formation of an eccentric thick end wall lesion rich in collagen fiber prevented atheromatous plaque from tearing off. However, the annual progression rate of the mean maximal intima-media thickness in the common carotid artery was 0.0002 mm/year in the LA group, which was significantly lower than the mean of 0.251 mm/year seen in the control group (drug therapy only group). In the patients with heterozygous FH (9 patients), the annual progression rate was lowered to 0.0023 mm/year, suggesting regression. The findings of the present study indicate that patients with severe FH refractory to drug treatment may benefit from more aggressive cholesterol lowering treatments such as LA combined with cholesterol lowering drug therapy. The progression of atherosclerosis may be prevented, plaque may be stabilized (regressed), and clinical events may be reduced as seen with patients with non-FH hypercholesterolemia.

Access site problems often cause serious complications in endovascular treatment. The aim of this study is to investigate whether a sheath-less nitinol stenting technique leads to reduce access site complications. This study was a single-center retrospective analysis of a prospectively maintained database. The study enrolled consecutive 98 patients with 111 lesions undergoing provisional stenting for de novo iliac artery or femoro-popliteal artery stenosis between August 2010 and November 2011. The patients were divided into two groups, a conventional procedure group and a sheath-less procedure group. The outcomes of this study were peri-procedural access site complications, initial success rate, procedure time, hemostatic time and bed-rest time. Forty-four lesions in 39 patients that treated using the sheath-less nitinol stent delivery technique were compared with 67 lesions in 59 patients treated using the conventional procedure. All procedures were successful. The incidence of pseudoaneurysm was significantly lower in the sheath-less procedure group than in the conventional procedure group (p = 0.043). However, there were no significant differences in any other complications. No significant difference was observed in the procedural time (p = 0.309). However, hemostatic time and bed-rest time were significantly shorter in the sheath-less procedure than in the conventional procedure (p < 0.0001). A sheath-less stenting technique reduced the access site incidence of pseudoaneurysm and did not increase other access site complications. Besides, this technique shortened hemostatic time and bed-rest time. The sheath-less stenting technique is considered to be a useful method for endovascular treatment.

To clarify the relationship between the dilatation of angiographically non-stenotic coronary artery segments in response to isosorbide dinitrate (ISDN), and serum lipids, 5 coronary segments in 7 patients with familial hypercholesterolemia (FH) and 43 patients with non-familial hypercholesterolemia (non-FH), who had either 1- or 2-vessel coronary heart disease, were investigated. The serum total cholesterol level was significantly greater in FH than in non-FH. Before and after the direct intracoronary injection of ISDN, coronary diameter was measured by a computer-assisted coronary angiography analysis system. The order of the dilative responses in coronary segments in non-FH patients (segments: #5 > #11 > #6 > #13 > #7) was exactly the same as the order of their original diameters, while the ratio of the increase in diameter (after/before ISDN injection) did not differ among any of the segments (mean: 1.08-fold increase). In the non-FH group, no correlation was found between the serum total cholesterol, triglyceride, low-density lipoprotein-cholesterol, or high-density lipoprotein-cholesterol, and the ratio of the coronary diameter after and before injection of ISDN. Moreover, hypercholesterolemia in non-FH did not affect the coronary dilative response to ISDN injection. In the FH group, although the original diameter of each segment did not differ from that in the non-FH group, the ratio of the diameter after and before injection of ISDN was significantly smaller in FH than in non-FH (p < 0.01). These results suggest that a non-stenotic coronary artery in FH has a lower capacity for vasodilation in response to ISDN. Although hypercholesterolemia was excluded as a factor which may suppress the capacity for coronary dilation in non-FH, spontaneous hypercholesterolemia in FH may affect medial smooth muscle functions of the coronary artery.

Aims We investigated the mechanism and predictors of jailed branch vessel (BV) compromise during the stenting of left main trunk (LMT) bifurcation lesions from a multidetector row computed tomography (MDCT) analysis. Methods and results Eighty patients who underwent MDCT and stenting for LMT bifurcation lesions were examined. The patients were retrospectively classified into a BV stenosis (BVS; n=38) group and a non-BV stenosis (NBVS; n=42) group according to a coronary angiography obtained just after crossover stent deployment for the target vessel (TV). The angle between the LMT and TV was significantly wider in the BVS group than in the NBVS group (140.2±10.3 degree vs. 132.6±14.2 degree, p=0.0076), and the frequency of carina side plaque at the TV in the long and short axis was significantly higher in the BVS group than in the NBVS group (50.0% vs. 16.7%; p=0.0012, 63.2% vs. 38.1%; p=0.0251, respectively). In a multivariate analysis, the presence of carina side plaque at the TV in the long and short axis were independent predictors of BVS (odds ratio: 5.15, p=0.0086, odds ratio: 3.83, p=0.0231, respectively). Conclusions The plaque distribution and morphology assessed by MDCT may provide useful information that can predict the potential compromise of the BV during treatment for an LMT bifurcation lesion.

We examined esophageal varices using the new technique of endoscopic ultrasonography (EUS) that employed a high-resolution 15/20 MHz ultrasonic probe. EUS employing the direct contact method, in which the forceps-channel probe was in direct contact with the lumen, was used in patients with esophageal varices (58 cases) and in control patients without varices (32 cases). Findings were also compared with additional EUS employing the conventional balloon method which was performed on 21 of the patients with esophageal varices. The direct contact method visualized all the varices (endoscopic Grade 1 varices; 2.0 ± 0.7 mm in diameter (mean ± SD) and 11.9 ± 3.1 cm in length, endoscopic Grade 2 or 3 varices; 5.8 ± 3.2 mm in diameter and 16.3 ± 3.0 cm in length). In the 21 patients who underwent EUS by the two different methods, varices were displayed by both methods in 9 cases (7 endoscopic Grade 2 varices, and 2 Grade 3 varices). In the other 12 cases (8 endoscopic Grade 1 varices, and 4 Grade 2 varices) varices were displayed only by the direct contact method, and not by the balloon method. The direct contact method can be regarded as a useful technique for the evaluation of esophageal varices.

Predicting the occurrence of acute coronary syndrome (ACS) is a major clinical challenge for cardiologists. Multi-slice computed tomography (CT) has enabled easy detection and assessment of atherosclerotic coronary plaque, and therefore has considerable potential in the prevention of ACS. The recent development of 64-slice cardiac CT enables detailed information on both plaque properties and characteristics to be obtained with excellent diagnostic accuracy. Cardiac CT therefore has great potential for detecting the unstable plaques that are prone to result in ACS. (Circ J 2011; 75: 2013-2018)

To examine the long-term outcome of the stent fracture (SF) and the potential predictive factors contributing to in-stent restenosis (ISR) in the fractured stent.The SF is thought to be a higher risk of ISR in drug-eluting stent, although SF does not always develop ISR.The consecutive 1,228 de novo lesions in 1,079 patients who underwent sirolimus-eluting stents implantation and assessed by 8 months follow-up coronary angiography were retrospectively analyzed.One hundred and seventeen SFs (9.5%) were identified in 100 patients and 22 (18.8%) SFs revealed ISR at the first follow-up. In addition, 16 (13.7%) developed new ISRs from 95 residual SFs without ISR prior to the second follow-up. Overall, 38 (32.5%) of all 117 SFs developed ISR, and 16 (42.1%) of 38 SFs occurred in a late phase beyond the first 8 months follow-up. A higher risk of ISR in the SF site was associated with the chronic total occlusion (ISR vs. no ISR: 34.2% vs. 16.5%, P = 0.0304), calcified lesions (55.3% vs. 34.2%, P = 0.0299), and correspondence 89.5% versus 43.0%, P0.0001 (SF site occurring at the original target lesion site) in the univariate analysis. The correspondence was identified as the only strong predictive factor for ISR at the SF site according to a multivariate logistic regression analysis (odds ratio 12.6, 95% confidence interval 3.82-53.5, P0.0001).SF occurring at the site of the original target lesion was a strong independent predictor of ISR. This indicates the need for a careful, long-term follow-up in those situations, even when no significant ISR is initially detected.

A 73-year-old diabetic man underwent multislice computed tomography (MSCT) and noncontrast T1-weighted (T1W) magnetic resonance imaging (MRI) for the evaluation of atypical chest discomfort after an exercise ECG was nondiagnostic. The MSCT demonstrated a low-density positive remodeling plaque and spotty calcification without significant stenosis in the proximal segment of the right coronary artery (Figure 1A and 1B). Noncontrast T1W MRI, using a 1.5-T MR system (Intera, Philips Medical Systems, Best, the Netherlands), revealed a hyperintense plaque (HIP) in the right coronary artery in an area corresponding to …

BACKGROUND Various two-stent techniques have been applied to aggressively treat bifurcation lesions as the introduction of drug-eluting stents (DES) and the importance of the bifurcation angle and three-dimensional (3D) structure has come to be recognized. Recent 64 multislice computed tomography (MSCT) technology provides accurate information about the 3D bifurcation geometry of the coronary arteries and with reproducibility. OBJECTIVES The purpose of this study is to disclose the coronary bifurcation angle and 3D structure in humans and elucidate the importance of bifurcation angle for the crush technique using MSCT. METHODS Two hundred and nine patients who were suspected to have angina pectoris and underwent CT angiography using MSCT were examined. The 3D-volume rendering (VR) image was reconstructed by two technicians and was used for the assessment of each coronary bifurcation angles. RESULTS The average LMT bifurcation angles (angle LMT-LAD, angle LMT-LCx, angle LAD-LCx) were 143 +/- 13 degrees , 121 +/- 21 degrees , and 72 +/- 22 degrees , respectively, the average angle LAD-D was 138 +/- 19 degrees , the average angle LCx-OM was 134 +/- 23 degrees , the average distal RCA bifurcation angles (angle RCA-4AV, angle RCA-4PD, angle 4AV-4PD) were 152 +/- 15 degrees , 137 +/- 20 degrees , and 61 +/- 21 degrees , respectively. In addition, a percentage of steep angled bifurcation (

We present the case of a 42-year-old male with familial hypercholesterolemia (FH) who had received long-term low-density lipoprotein (LDL)-apheresis before death occurred, presumably from an arrhythmia. He had been treated with double filtration plasmapheresis (DFPP) for 4 years and selective LDL adsorbent plasmapheresis (LAPP) for 2 years and 7 months. During the period of treatment (6 years and 7 months) he had received a total of 129 sessions of LDL-apheresis. Serum total cholesterol of the patient before the treatment was 638 mg/dl and during the treatment, the time-averaged values ranged from 336 mg/dl to 411 mg/dl for the first 4 years (with DFPP) and from 257 mg/dl to 364 mg/dl for the sequential 2 years and 7 months (with LAPP). Coronary angiograms were analysed for 13 segments of the coronary arteries using a digitized processing system. Analysis documented regression by identifying a reduction in percent stenosis from 34% to 20% in the proximal left circumflex artery (LCX), from 78% to 61% in the proximal right coronary artery (RCA), and from 92% to 72% in the middle RCA. In the other 10 segments analysed no significant regression and no progression were observed. The autopsy findings of the step-wise serial sections of the native coronary arteries did not record the formation of new and/or typical atheroma. In addition, a thickened intima, and an eccentric thickened wall lesion rich in collagen fiber were observed, although an accumulation of foam cells in the thickened wall lesions was found in some segments. This observation suggested scarring of the atheromatous plaque. We confirmed that LDL-apheresis performed over a period of 6 years and 7 months induced angiographic regression of coronary atherosclerosis in the patient with FH, and found that most of the atherosclerotic lesions were changed pathologically into sclerotic lesions rich in collagen fiber.

We have evaluated the effects of LDL-aphereses performed over 15 to 62 months, involving both Double Filtration Plasmapheresis (DFPP) and LDL Adsorbent Plasmapheresis (LAPP), for 5 patients with familial hypercholesterolemia (FH) (1; homozygous, and 4; heterozygous) using computer image analysis by coronary angiography, (CAG). Results by CAG showed that in homozygous FH, 9 (75%) of 12 segments demonstrated no progression, 2 (16.7%) segments showed regression, and only 1 (8.3%) segment showed progression. In heterozygous FH, 27 (81.8%) of 33 segments showed progression, and 6 (18.2%) segments showed regression. Aorto coronary bypass was beneficial with obtained patency in 13 (93%) of the 14 grafts. We also performed an autopsy on one patient, with heterozygous FH who died suddenly probably due to fibrillation. The patient had received long-term LDL apheresis for 6 years and 7 months and had shown angiographic regression. The pathological findings showed no typical or new atheroma, significant cicatrization in the thickened intima and an eccentric thickened wall lesion. The serial angiographic findings together with the pathological findings very clearly support the use of LDL-apheresis for producing "true" regression in coronary atherosclerosis in FH.

Purpose We examined the importance of prolonged inflation time for optimal sirolimus-eluting stent (SES) or paclitaxel-eluting stent (PES) expansion. Methods Eighty-one de novo lesions deployed single SES or PES between April 2007 and March 2008 were divided into four groups; group 1: 21 SES deployed at 20 atm x 60 sec, group 2: 20 SES deployed with 2-step inflation at 20 atm x 60 sec following 20 atm x 20 sec, group 3: 20 PES deployed same as group 1, group 4: 20 PES deployed same as group 2. The minimal lumen diameter (MLD) and stent expansion ratio (SER; stent cross- sectional area at lesion/balloon cross-sectional area which was calculated according to the compliance chart at the same atmosphere as stent deployment) were compared between group 1 and group 2 in SES, between group 3 and group 4 in PES. Results The MLD of post 60 sec was significantly higher than that of post 20 sec (2.84 +/- 0.28 mm in group 1, 2.76 +/- 0.33 mm in group 2 vs. 2.54 +/- 0.33 mm in group 2; P = 0.003, 0.045, respectively and 2.94 +/- 0.28 mm in group 3, 3.00 +/- 0.34 mm in group 4 vs. 2.69 +/- 0.35 mm in group 4; P = 0.022, 0.007, respectively). The SER of post 60 sec was significantly higher than that of post 20 sec (79.3% +/- 8.5% in group 1, 80.8% +/- 7.8% in group 2 vs. 71.1% +/- 10.2% in group 2; P = 0.014, 0.011, respectively and 81.1% +/- 7.9% in group 3, 84.3% +/- 9.9% in group 4 vs. 72.6% +/- 10.5% in group 4, P = 0.011, 0.001, respectively). Conclusion The prolonged delivery inflation for 60 sec may result in a more optimal stent expansion. It is therefore considered to be a useful method for deploying drug-eluting stent.

This study sought to characterize coronary hyperintense plaques (HIP) using noncontrast T(1)-weighted imaging (T1WI) in cardiac magnetic resonance, which was then compared with multislice computed tomography and intravascular ultrasound.Carotid plaque components such as intraplaque hemorrhages and/or lipid-rich necrotic cores can be detected as HIP by noncontrast T1WI. Although coronary HIPs have been successfully detected using this technique, the properties of hyperintense signals in coronary plaques have not yet been systematically evaluated.Thirty-eight lesions from 37 patients with angina pectoris who demonstrated70% coronary stenosis on multislice computed tomography were evaluated by noncontrast T1WI using a 1.5-T magnetic resonance imager, and 25 lesions were evaluated by intravascular ultrasound. Signal intensity of coronary plaque to cardiac muscle ratio1.0 was defined as HIP. We divided 25 lesions into the 2 groups, according to the presence or absence of HIP: HIP (n = 18) and non-HIP (n = 7) groups.In comparison with the non-HIP group, the HIP group demonstrated significantly higher coronary plaque to cardiac muscle ratio (1.7 +/- 0.7 vs. 0.9 +/- 0.1, p0.01), higher frequency of positive remodeling as observed by both multislice computed tomography (89% vs. 0%, p0.0001) and intravascular ultrasound (94% vs. 14%, p0.001) and ultrasound attenuation (100% vs. 14.3%, p0.0001). The frequency of spotty calcification tended to be higher in HIP (89% vs. 50%, p = 0.079). The HIP group also exhibited a significantly lower computed tomography density (-23.2 +/- 20.7 Hounsfield units [HU] vs. 9.6 +/- 20.5 HU, p0.01). In addition, the incidence of transient slow-flow phenomena was significantly higher in the HIP group than in the non-HIP group (83% vs. 14%, p0.01).The typical HIP case was associated with ultrasound attenuation, positive remodeling, remarkably low computed tomography density, and a high incidence of slow-flow phenomena. Noncontrast T1WI in cardiac magnetic resonance imaging may be useful for the assessment of coronary plaque characterization in patients with coronary artery disease.