Comparison of clinical outcomes of coronary artery stent implantation in patients with end-stage chronic kidney disease including hemodialysis for three everolimus eluting (EES) stent designs: Bioresorbable polymer-EES, platinum chromium-EES, and cobalt chrome-EES.

BACKGROUNDS: New-generation bioresorbable polymer-everolimus eluting stents (BP-EES) are available. This study aimed to compare the clinical outcomes for BP-EES compared to more established stent designs, namely the platinum chromium-EES (PtCr-EES) and cobalt chrome-EES(CoCr-EES) in patients with the end-stage chronic kidney disease (CKD) including hemodialysis (HD). METHODS: One-hundred-forty-one consecutive stents (BP-EES [n = 44], PtCr-EES [n = 45], and CoCr-EES [n = 52]) were implanted in 104 patients with CKD. All patients underwent a follow-up coronary angiography at 12 months after implantation. End-stage CKD was defined as an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 , or the need for HD. The following outcome variables were compared among the three stent groups after implantation and the 12-month follow-up: target lesion revascularization (TLR), stent thrombosis (ST), and major adverse cardiac event (MACE). Minimal stent diameter (MSD) and %diameter-stenosis (%DS) were measured using quantitative coronary angiography. RESULTS: The overall rate of TLR and MACE was 14.6% and 30.8%, respectively, with no incidence of ST. Immediately after implantation, the MSD (P = 0.22) and %DS (P = 0.42) were equivalent among the three groups. However, at the 12-month follow-up, a tendency towards higher TLR was observed for the BP-EES group (22.7%) compared with the PtCr-EES (8.8%) and CoCr-EES (9.6%) groups (P = 0.07). Late loss in lumen diameter was also significantly greater for the BP-EES (0.51 ± 0.64 mm) group than either the PtCr-EES (0.20 ± 0.61 mm) and CoCr-EES (0.25 ± 0.70 mm) groups (P = 0.03). CONCLUSIONS: BP-EES might increase the risk of in-stent restenosis in patients with end-stage of CKD or the need for HD.

Fusobacterium necrophorum Endocarditis with Liver Abscesses: A Case Report and Review of the Literature.

Fusobacterium necrophorum is a very rare cause of endocarditis. We herein report a case of F. necrophorum endocarditis with liver abscesses in a 51-year-old woman. This is the first reported case of monomicrobial F. necrophorum endocarditis to present in a patient over 50 years old. We also reviewed 10 reported cases, including the present case. Our review indicated that anaerobic bacteria, including Gram-negative anaerobic bacilli such as F. necrophorum, should be considered in the differential diagnosis of infective endocarditis, especially in patients without preexisting organic heart disease.

Impaired glucose tolerance and future cardiovascular risk after coronary revascularization: a 10-year follow-up report.

AIMS: Practical management guidelines for impaired glucose tolerance (IGT) have not been established. Although IGT is a potent marker of cardiovascular disease (CVD), it is still controversial whether its magnitude of CVD risk is comparable to that of frank diabetes. Moreover, information on long-term clinical outcomes of IGT patients undergoing coronary revascularization is limited. The aim of the present work was to investigate the 10-year prognostic impact of IGT in comparison with diabetes in patients with CAD undergoing coronary revascularization. METHODS: This cohort recruited from two Japanese clinical sites included patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) between 2004 and 2008. Patients were categorized into previously known diabetes (PKD, n = 197), newly diagnosed diabetes (NDD, n = 51), and IGT (n = 50) groups according to oral glucose tolerance test results except for PKD. The primary end point was defined as a composite of cardiovascular death, myocardial infarction, stroke, repeat revascularization, and heart failure hospitalization. RESULTS: The cumulative risk of the primary outcome was significantly higher in the PKD and IGT than in the NDD (log-rank test p = 0.017). A Cox proportional hazards model demonstrated that IGT (hazard ratio [HR], 7.91; 95% confidence interval [CI], 1.84-27.58) and creatinine clearance (HR, 7.89, 95% CI, 2.73-19.10) were predictors of long-term CVD risk, while NDD and PKD were not. CONCLUSIONS: IGT significantly increased the long-term risk of developing CVD in patients with CAD after PCI compared with diabetes.

Atrial Fibrillation Had Less Impact on the Risk of Ischemic Stroke in Non-anticoagulated Patients Undergoing Hemodialysis: Insight from the RAKUEN study.

Objective The progress of non-anticoagulated patients with atrial fibrillation (AF) undergoing hemodialysis has not been determined. Using data from the RAKUEN (Registry of Atrial fibrillation in chronic Kidney disease Under hEmodialysis from Niigata) study, we examined the clinical characteristics and outcomes among hemodialysis patients with AF who were not receiving a vitamin K antagonist (VKA). Methods and Results Forty-three of 423 patients undergoing hemodialysis (-10%) were prescribed a VKA. The remaining 380 patients (age 64.8±12.8 years, male 70%) were enrolled in the present study. During a mean observation period of 36 months, AF (n=55) was independently associated with all-cause death (hazard ratio, 1.82; 95% confidence interval, 1.12-2.94; p=0.014), but was not associated with ischemic stroke (hazard ratio, 1.91; 95% confidence interval, 0.74-4.92; p=0.177) and major bleeding (hazard ratio, 1.80; 95% confidence interval, 0.80-4.08; p=0.150). The crude incidence rates of all-cause death and ischemic stroke in the AF patients were 15.75 (2.5-fold higher compared to the non-AF patients) and 3.63 (1.7-fold higher compared to the non-AF patients) per 100 person-years, respectively. Conclusion A great impact on death, but not ischemic stroke, was observed in non-anticoagulated hemodialysis patients with AF in comparison to those without AF from the analysis of the RAKUEN study.

Cardiovascular Outcomes in Patients With Previous Myocardial Infarction and Mild Diabetes Mellitus Following Treatment With Pioglitazone: Reports of a Randomised Trial From The Japan Working Group for the Assessment Whether Pioglitazone Protects DM Patients Against Re-Infarction (PPAR Study).

BACKGROUND: Secondary prevention in patients with myocardial infarction (MI) is critically important to prevent ischaemic heart failure and reduce social burden. Pioglitazone improves vascular dysfunction and prevents coronary atherosclerosis, mainly via anti-inflammatory and antiatherogenic effects by enhancing adiponectin production in addition to antihyperglycemic effects, thus suggesting that pioglitazone attenuates cardiovascular events in patients with mild (HbA1c levels < 6·5%) diabetes mellitus (DM). Therefore, we evaluated the effects of pioglitazone on cardiovascular events in patients with both previous MI and mild DM. METHODS: In this multicentre, prospective, randomised, open, blinded-endpoint trial, we randomly assigned 630 patients with mild DM with a history of MI to undergo either DM therapy with (pioglitazone group) or without (control group) pioglitazone. DM was diagnosed using the 75-g oral glucose tolerance test, and mild DM was defined if HbA1c level was < 6·5%. The primary endpoint was the composite of cardiovascular death and hospitalisation caused by acute MI, unstable angina, coronary revascularisation (including percutaneous coronary intervention and cardiac bypass surgery), and stroke. FINDINGS: HbA1C levels were 5·9 and 5·8% (p = 0·71) at baseline and 6·0 and 5·8% (p < 0·01) at 2 years for the control and pioglitazone groups, respectively.The primary endpoint was observed in 14·2% and 14·1% patients in the control and pioglitazone groups during two years (95% confidential interval (CI):0.662-1·526, p = 0·98), respectively; the incidence of MI and cerebral infarction was 0·3% and 2·2% (95%CI: 0·786-32·415, p = 0·09) and 1·0% and 0·3% (95%CI: 0·051-3·662, p = 0·44), respectively. Post-hoc analyses of the 7-year observation period showed that these trends were comparable (21·9% and 19·2% in the control and pioglitazone groups, 95%CI: 0.618-1·237, p = 0·45). INTERPRETATION: Pioglitazone could not reduce the occurrence of cardiovascular events in patients with mild DM and previous MI.

Clinical characteristics of hemodialysis patients with atrial fibrillation: The RAKUEN (Registry of atrial fibrillation in chronic kidney disease under hemodialysis from Niigata) study.

BACKGROUND: Clinical characteristics, management, and outcomes in hemodialysis patients with atrial fibrillation (AF) remain unclear. METHODS AND RESULTS: We studied 423 Japanese patients undergoing maintenance hemodialysis (age 65.2±12.4 years, male 70%, mean duration of hemodialysis 139±124 months). AF was present in 19% (n=82) and was independently related to increased age (odds ratio 1.070, 95% confidence interval 1.043-1.098), longer hemodialysis duration (odds ratio 1.006, 95% confidence interval 1.004-1.008), and congestive heart failure (odds ratio 2.749, 95% confidence interval 1.546-4.891). During observations lasting a mean of 36 months, the incidences of all-cause death, cardiovascular death, and major bleeding, in particular gastrointestinal bleeding, were significantly higher in the AF (n=82) than the non-AF (n=341) patients (p<0.001, p=0.004, p=0.002, p=0.027, respectively), but the incidence of ischemic stroke/systemic embolism was similar in the AF and non-AF patients. AF was independently associated with all-cause death (hazard ratio 1.728, 95% confidence interval 1.123-2.660) and major bleeding (hazard ratio 1.984, 95% confidence interval 1.010-3.896). Warfarin was prescribed in 33% of the AF patients, but the rates of all-cause death, ischemic stroke, and major bleeding during the study period were not significantly different between warfarin (n=27) and non-warfarin (n=55) groups. CONCLUSIONS: In our hemodialysis patients, AF was a common comorbidity and was independently associated with all-cause death and major bleeding, but not with increased risk of ischemic stroke.

Multiple bilateral coronary-biventricular fistulas with elevated left ventricular end-diastolic pressure.

Arterioventricular fistulas are relatively rare abnormalities and the etiology may be congenital or traumatic. We report a case of a 51-year-old woman in which all three coronary arteries emptied into both ventricles via multiple small fistulas resulting in elevated left ventricular end-diastolic pressure.

Systolic dysfunction in urban Japan.

BACKGROUND: Heart failure (HF), which can be caused by left ventricular systolic dysfunction (LVSD), is a growing problem in developed countries with a large aging population. The aim of the present study was to characterize outpatients with LVSD in the adult population (45-84 years) in an urban Japanese community (Niigata City), and delineate their characteristics in comparison with those in a rural one (Sado). METHODS AND RESULTS: Over a 5-year period, 1,297 patients (67% males) with LVSD (defined as ejection fraction < or =50%) were extracted from 87,953 echocardiography records available in 15 hospitals in Niigata City. The proportion of LVSD increased progressively with age (p-for-trend <0.0001), reaching 1-2% in those aged > or =75 years. The prevalence of comorbidities was noticeable (47% had hypertension, 41% myocardial ischemia, 34% atrial fibrillation, 33% previous hospitalization because of congestive HF, 27% cerebral stroke). In comparison with Sado, Niigata patients were younger, with a higher prevalence of comorbidities (hypertension, diabetes, dyslipidemia, and cerebral stroke). CONCLUSIONS: As the proportion of LVSD cases increases progressively with age, it is expected to simulate a future epidemic. The differences between patients' characteristics and disease patterns in urban and rural communities may favor individually tailoring preventive strategies for HF in these areas.

Effects of 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS) and chlorpromazine on NO3- transport via anion exchanger in erythrocytes: inertness of DIDS in whole blood.

We examined the effects of chlorpromazine on NO(3)(-) transport between erythrocytes (RBCs) and extracellular fluid. Chlorpromazine (10 microg/ml) did not influence NO(3)(-) movement in both whole blood and RBC suspension. Though an anion exchanger (AE1) inhibitor DIDS (4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid, 100 microM) did not alter NO(3)(-) movement in whole blood, it inhibited the movement in a concentration-dependent manner in the RBC suspension. The inhibition was abrogated by plasma and albumin concentration-dependently. Our results indicated that chlorpromazine had no effect on NO(3)(-) transport through AE1 and that the inertness of DIDS on AE1 in whole blood is due to interference by albumin in plasma.

Levels of soluble E-selectin and ICAM-1 in the coronary circulation of patients with stable coronary artery disease: association with the severity of coronary atherosclerosis.

The recruitment of circulating leukocytes to atherosclerotic sites is mediated by a family of adhesion molecules. The objective of the present study was to evaluate the relationship between circulating adhesion molecule levels in the coronary circulation and the severity of coronary atherosclerosis in patients with stable coronary artery disease. The subjects were 79 patients undergoing coronary angiography. According to the severity of coronary atherosclerosis as assessed by the Gensini Score (GS) of the left coronary artery, they were classified into three groups: group C (no organic stenosis, score 0, n = 14), group M (mild organic stenosis, score 1-13, n = 39) and group S (severe organic stenosis, score > or = 14, n = 26). Blood samples were taken from the aorta (Ao) and coronary sinus (CS), and plasma levels of soluble E-selectin (sE-selectin) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured by enzyme-linked immunosorbent assay. These levels were then compared between groups. There were no significant differences in plasma sICAM-1 levels in the Ao or CS between the three groups. The difference in sICAM-1 levels between the CS and Ao (CS-Ao) also showed no significant difference. Plasma sE-selectin levels in both the Ao and CS were significantly higher in group S than in groups C and M (p < 0.05), but there were no significant differences in CS-Ao. There was a weak but significant correlation between the plasma levels of these adhesion molecules and the number of coronary risk factors present. Multivariate analysis showed that the number of coronary risk factors was the only positive predictor (p = 0.0048) of the GS; there was no association between the plasma level of either adhesion molecule and the GS. In patients with stable coronary artery disease, sICAM-1 plasma levels do not indicate the severity of coronary atherosclerosis, while sE-selectin plasma levels appear to reflect the severity of systemic rather than coronary atherosclerosis.

Plasma concentrations of monocyte chemoattractant protein 1 (MCP-1) and neopterin in the coronary circulation of patients with coronary artery disease.

BACKGROUND: The dynamics of MCP-1 and neopterin and the relation between their concentrations in coronary circulation and the severity of coronary atherosclerosis were evaluated in patients with stable coronary artery disease (CAD). METHODS AND RESULTS: Blood samples were obtained from the aortic root (Ao) and coronary sinus (CS) of 78 patients who underwent coronary angiography. Plasma MCP-1 and neopterin concentrations were measured using an enzyme-linked immunosorbent assay method and the CS-Ao differences were calculated. The severity of coronary heart disease (CHD) was evaluated in 52 patients who had no history of coronary angioplasty, using 3 coronary scoring systems: the clinical 1- to 3-vessel disease score, the American Heart Association extension score (1-15 segments), and the Gensini score. The plasma MCP-1 and neopterin concentrations increased significantly with age. The CS-Ao differences for neopterin showed weak, but significant, positive correlation with the Gensini score (r=0.347, p=0.013). There were no correlations among the MCP-1 concentrations in the Ao or CS, or in the CS-Ao difference, with the severity of CHD. CONCLUSIONS: The results indicate that neopterin is a useful marker of the severity of coronary atherosclerosis in patients with stable CAD, acting as an index of the activity of monocytes/macrophages.

Association between coronary endothelial dysfunction and local inflammation of atherosclerotic coronary arteries.

We have examined a possibility whether or not severity and extent of coronary atherosclerosis may associate with degree of local inflammation in relation to endothelial dysfunction as is indicated by reduced NO formation. Blood samples were obtained from aortic root (Ao) and coronary sinus (CS) of 39 patients who underwent coronary angiography. Plasma NOx levels (nitrite + nitrate, stable NO end-products) were evaluated by HPLC-Griess system, and markers of inflammation, C-reactive protein (CRP) and serum amyloid A protein (SAA), were measured by Latex Turbidimetric Immunoassay. To evaluate the changes of these substances through coronary circulation, the percentage changes of respective markers [(CS - Ao) x 100/Ao] were calculated. The extent and severity of atherosclerosis of left coronary arteries were evaluated with Gensini Score (GS). The GS correlated with the percentage changes of NOx (r = -0.35, p < 0.05) and that of SAA (r = 0.43, p < 0.05) across coronary circulation, but not with changes in CRP. Moreover, the percentage changes of NOx correlated with that of SAA (r = -0.36, p < 0.05). These results indicated that severity and extent of coronary atherosclerosis related to degree of local inflammation which has a possible association with coronary endothelial dysfunction.

Decrease in plasma NOx concentration by isosorbide dinitrate, an organic nitrate ester.

It has been suggested that isosorbide dinitrate (ISDN)-induced venodilation could be ascribed to preferential accumulation of the agent in venous tissues, resulting in higher concentrations of nitric oxide (NO). Here, the authors investigated whether the venodilating effect of ISDN is associated with a preferential increase in plasma concentrations of NOx (NO2- and NO3-, stable end-products of NO) in venous blood than arterial blood. Plasma NOx was measured by high-performance liquid chromatography-Griess system with a sensitivity of 0.01 microM for NO2- and 0.1 microM for NO3-. Arterial and venous blood samples were obtained after coronary angiography from the aorta and right atrium of patients with or without ischemic heart disease. Nicardipine, a calcium channel blocker, was used as a non-NO-related arteriovasodilator. At 1 mg i.v., it did not cause any changes in NOx concentration in arterial and venous blood irrespective of hemodynamic changes. However, ISDN (3 mg i.v.) increased NO2- and decreased NO3- in both arterial and venous blood, with concomitant venodilation. Further analysis revealed that plasma NO increased in the pulmonary circulation and this increase was preserved after nicardipine and ISDN, and that ISDN, but not nicardipine, increased plasma NO3- in the pulmonary circulation. The authors did not detect higher concentrations of NOx in venous blood relative to their level in arterial blood. Further studies are necessary to clarify the kinetics of NO and NO-related compounds in the whole body.

Significance of asymmetric dimethylarginine (ADMA) concentrations during coronary circulation in patients with vasospastic angina.

The basal activity of nitric oxide (NO) is reduced in spastic arteries of patients with vasospastic angina (VSA). Elevated concentrations of ADMA are associated with reduced NO production and impaired endothelium-dependent vasodilatation. The aim of this study was to elucidate the role of ADMA and its relationship to NO end-products (NOx; nitrate + nitrite) during coronary circulation in patients with VSA. The plasma ADMA and NOx concentrations during coronary circulation were evaluated in 16 VSA and 16 control patients. Blood samples were obtained from the coronary sinus (V) and the ostium of the left coronary artery (A), and the (V-A) differences of ADMA and NOx were determined. The coronary sinus plasma ADMA concentration in patients with VSA was higher than that in the control. The coronary sinus - arterial (V-A) difference of NOx was negative in the VSA group and approximately zero in the control group (VSA group =-1.4 micromol/L, control group =-0.1 micromol/L, p=0.0005). Furthermore, in the VSA patients, there was a negative correlation between the (V-A) difference of NOx and the basal coronary artery tone at the site of spasm (r=-0.60, p=0.015). A significant negative correlation between the (V-A) differences of NOx and ADMA was observed in patients with VSA (r=-0.52, p<0.05), but not in those of the control. Higher ADMA concentrations might cause the reduced formation of NO that underlies the pathophysiology of coronary vasospasm.

Acute pulmonary thromboembolism induced by prophylactic heparin use and a heparin-coated catheter: a case of heparin-induced thrombocytopenia and thrombosis syndrome.

Heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) is a potentially life-threatening side effect of heparin therapy, triggered by an immune response, and has been reported to be related not only to the therapeutic use of heparin but also to heparin-coated catheters. A 45-year-old woman with intrapelvic malignancy developed an acute pulmonary thromboembolism (PE) after hysterectomy despite prophylactic heparin use. Subsequent large doses of heparin for treatment of the PE exacerbated the thrombocytopenia and, moreover, a large thrombus formed around the heparin-coated central venous catheter. Anti-heparin-platelet factor 4 complex antibody and heparin-induced platelet aggregation assay were positive, so the diagnosis was HITTS, and heparin was replaced by argatroban after carrying out thrombectomy. This therapy was successful, and the patient made favorable progress.

Plasma levels of soluble thrombomodulin, C-reactive protein, and serum amyloid A protein in the atherosclerotic coronary circulation.

Plasma levels of C-reactive protein (CRP) and serum amyloid A protein (SAA), inflammatory markers, and soluble thrombomodulin (s-TM), a marker of endothelial damage. are thought to be related to coronary artery disease. However, the relationship between these inflammatory markers and endothelial injury in atherosclerotic coronary arteries is still unclear. Fifty-five patients who underwent coronary angiography were classified into 3 groups according to the severity of left coronary arterial atherosclerosis evaluated by the Gensini score (GS; normal: score = 0, n = 15; mild: 0 < score < 15, n = 29; severe: score > or = 15, n = 11). Blood samples were obtained from the aortic root (Ao) and coronary sinus (CS) and plasma CRP and SAA levels were measured by latex turbidimetric immunoassays, and s-TM levels were determined by an enzyme-linked immunosorbent assay. The difference between marker concentrations in the Ao and CS of the coronary circulation was expressed as the coronary sino-arterial (CS-Ao) difference. The CS-Ao differences of s-TM and SAA were significantly higher in patients with severe atherosclerosis than in normal patients (P < 0.01), and showed weak but significant positive correlations with the GS (r = 0.34, P < 0.01 and r = 0.33, P < 0.05, respectively). The CS-Ao differences in CRP did not differ among the three groups, and did not correlate with the GS. The results of our study reveal a possible relationship between endothelial cell injury and inflammation in atherosclerotic coronary arteries.