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ABSTRACT: BACKGROUND: Aortic stenosis (AS) is recognized as a cause of sudden cardiac death. Recently, the measurement of high-sensitivity troponin T (hs-TnT) has become possible. Several studies have clarified that hs-TnT is a marker to indicate mortality of cardiovascular diseases. OBJECTIVES: To examine whether hs-TnT can be used as a prognostic marker to predict the operative outcome of AS. METHODS: We enrolled 60 patients with AS (mean age=68.7±9.6 years, male/female=30/30). Cardiac catheterization and echocardiography were performed to evaluate the severity of AS. Aortic valve replacement surgery was performed in all patients. We defined major adverse cardiac events (MACE) as composite events of heart failure, fatal arrhythmia, and all causes of death. RESULTS: We followed up the patients for 922±800 days. Mean left ventricular ejection fraction was 60.0±1.8%. Mean aortic valve area was 0.61±0.03cm2. MACE occurred in 11 patients (18%), including 5 sudden cardiac deaths. We divided the patients into three groups based on the percentile of the plasma levels of hs-TnT. Kaplan-Meier curve revealed a statistically significant difference in MACE rate among the groups (log-rank test, χ2=13.0, p=0.002). We conducted a Cox proportional hazard analysis with a model including age, sex, estimated glomerular filtration rate, and hs-TnT tertile as explanatory variables to predict MACE. We found that hs-TnT tertile to be a significant factor to predict MACE (hazard ratio: 3.71, p=0.03). CONCLUSIONS: hs-TnT can be a prognostic marker for patients with AS after valve replacement surgery.
Journal of Cardiology 03/2013; · 1.28 Impact Factor
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Jun Mimuro,
Hiroaki Mizukami,
Shuji Hishikawa, Tomokazu Ikemoto,
Akira Ishiwata,
Asuka Sakata,
Tsukasa Ohmori,
Seiji Madoiwa,
Fumiko Ono,
Keiya Ozawa,
Yoichi Sakata
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ABSTRACT: Neutralizing antibodies (NAbs) against adeno-associated viruses (AAVs) are known to interfere with AAV vector-mediated gene transfer by intravascular delivery. Evading the inhibitory effects of antibodies against AAV vectors is necessary for efficient transfer of therapeutic genes clinically. For this purpose, we tested the efficacy of saline flushing in order to avoid contact of vectors with NAbs present in blood. Direct injection of the AAV8 vector carrying the factor IX (FIX) gene into the portal vein of macaques using saline flushing achieved transgene-derived FIX expression (4.7 ± 2.10-10.1 ± 5.45% of normal human FIX concentration) in the presence of NAbs. Expression was as efficient as that (5.43 ± 2.59-12.68 ± 4.83%) in macaques lacking NAbs. We next tested the efficacy of saline flushing using less invasive balloon catheter-guided injection. This approach also resulted in efficient expression of transgene-derived FIX (2.5 ± 1.06-9.0 ± 2.37%) in the presence of NAbs (14-56× dilutions). NAbs at this range of titers reduced the efficiency of transduction in the macaque liver by 100-fold when the same vector was injected into mesenteric veins without balloon catheters. Our results suggest that portal vein-directed vector delivery strategies with flushing to remove blood are efficacious for minimizing the inhibitory effect of anti-AAV antibodies.Molecular Therapy (2012); doi:10.1038/mt.2012.258.
Molecular Therapy 12/2012; · 6.87 Impact Factor
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ABSTRACT: Background: S100A12, a calgranulin family protein released from white blood cells, is involved in inflammatory cardiovascular disease. It was hypothesized that the plasma level of S100A12 can be used to predict outcome in patients with chronic coronary artery disease (CAD). The purpose of this study was to clarify the clinical significance of S100A12 in patients with stable CAD. Methods and Results: A total of 652 patients with stable CAD were studied. All patients underwent percutaneous coronary intervention and successful revascularization. Major adverse cardiovascular events (MACE) were defined as a composite of events of CHF, recurrence of angina pectoris, acute myocardial infarction, stroke, critical arrhythmia, intervention to peripheral arteries and cardiac death. The mean follow-up period was 973±639 days. MACE occurred in 108 patients (16.6%). Plasma S100A12 level had a significant positive correlation with high-sensitivity C-reactive protein (hs-CRP) level. On Kaplan-Meier curve analysis the incidence of MACE was significantly different among S100A12 quartiles (P=0.026). The highest S100A12 quartile (Q4) had a significantly higher MACE rate than the lowest quartile (Q1) (P=0.002). In contrast, hs-CRP was not significant for predicting MACE in the present subjects (P=0.074). A Cox proportional hazard model showed that S100A12 was an independent factor for predicting MACE in multivariate models. Conclusions: S100A12 could be a novel biomarker for predicting cardiovascular events for predicting MACE in patients with stable CAD. (Circ J 2012; 76: 2647-2652).
Circulation Journal 07/2012; 76(11):2647-52. · 3.77 Impact Factor
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ABSTRACT: A 52-year-old woman with Takayasu arteritis developed acute coronary syndrome and received percutaneous coronary intervention (PCI). The patient experienced restenosis three times even with drug-eluting stent (DES) implantation. We started steroid administration after the fourth PCI to reduce inflammation due to autoimmunity. With DES and a steroid combination, the patient remained free of chest pain, and a follow-up angiography demonstrated good patency of the stent site. Since in-stent restenosis may result from a complicated combination of neointimal proliferation and autoimmune mechanisms, physicians should consider a combination of DES and a steroid for the treatment of coronary artery disease in Takayasu arteritis.
Internal Medicine 01/2012; 51(7):739-43. · 0.94 Impact Factor
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Tsukasa Ohmori,
Yuichiro Yano,
Asuka Sakata, Tomokazu Ikemoto,
Masahisa Shimpo,
Seiji Madoiwa,
Takaaki Katsuki,
Jun Mimuro,
Kazuyuki Shimada,
Kazuomi Kario,
Yoichi Sakata
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ABSTRACT: High residual platelet aggregability during thienopyridine treatment occurs because of low levels of the active drug metabolite, and is associated with an increased rate of major adverse cardiovascular events. Recent findings suggest that paraoxonase-1 (PON1) is a major determinant for clopidogrel efficacy. The aim of this study was to assess the impact of serum PON1 activity on platelet aggregability in thienopyridine-treated patients. In 72 patients receiving treatment with aspirin and ticlopidine after acute coronary syndrome, various laboratory data including the formation of platelet aggregations induced by agonists were compared with serum PON1 activities, measured as paraoxonase and homocysteine thiolactone hydrolase (HTLase). Serum paraoxonase activity was significantly associated with HTLase activity (R=0.4487, P<0.0001). These PON1 activities were not correlated with any parameters for platelet aggregation, hypertension, sleep apnea, and diabetes mellitus. In contrast, serum PON1 activities seemed to be involved in cardiac function, with brain natriuretic peptide and ejection fraction being significantly correlated with serum HTLase activity (R=-0.2767, P=0.0214) and paraoxonase activity (R=0.2558, P=0.0339), respectively. Paraoxonase activity also demonstrated a significant association with increased levels of ankle-brachial index (R=0.267, P=0.0255). Serum PON1 activities did not influence platelet aggregability during treatment with thienopyridine. However, they might modulate cardiac function after acute coronary syndrome and progression of atherosclerosis.
Thrombosis Research 11/2011; 129(4):e36-40. · 2.44 Impact Factor
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ABSTRACT: Recent clinical studies have revealed that the expression of endoglin, an accessory protein for the TGF-β receptor, is increased in patients with atherosclerotic diseases. The plasma endoglin level is thought to represent endothelial activation, inflammation, and senescence. To clarify the significance of plasma endoglin in chronic coronary artery disease. Human umbilical vein endothelial cells (HUVECs) were cultured to examine changes in soluble endoglin (s-endoglin) levels caused by atherogenic stimulation in vitro. We studied 318 patients with stable coronary artery disease who underwent a successful percutaneous coronary intervention (PCI). Patients with acute coronary syndrome were excluded. Major adverse cardiovascular events (MACE) were congestive heart failure, acute myocardial infarction, stroke, and sudden cardiac death. All patients were followed-up to examine MACE after the procedure. We confirmed that the levels of s-endoglin was increased in the culture medium of HUVECs by senescence, tumor necrosis factor-α and hydrogen peroxide. In a clinical study, mean follow-up period was 1055 ± 612 days (49-2136 days) with 27 incidents of MACE (8.5%). We divided patients into three groups according to the plasma s-endoglin levels. Kaplan-Meier curves revealed that the highest endoglin group had a significantly higher MACE rate than the lowest endoglin group (log-rank test, p = 0.009). A Cox proportional hazards model showed that chronic kidney disease, left ventricular ejection fraction and s-endoglin level were significant factors to predict MACE. Plasma endoglin could be a marker to predict cardiovascular events in patients with chronic coronary artery disease after PCI.
Heart and Vessels 06/2011; 27(4):344-51. · 2.05 Impact Factor
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ABSTRACT: To elucidate the role of granzyme B in coronary artery disease (CAD) in patients with chronic kidney disease (CKD). We hypothesized that granzyme B plays an important role in the formation of coronary artery lesions in patients with CKD.
We studied 141 patients (116 men and 25 women; mean age, 64.2±9.6 years) and 16 control subjects. Diagnosis of CAD was confirmed by selective coronary angiography. CKD was defined as a sustained decrease in the estimated glomerular filtration (eGFR) rate less than 60 mL/min/1.73 m(2) over 3 months. We assigned patients to three groups: CAD without CKD (CAD group, n=46), CKD without CAD (CKD group, n=18), and CAD with CKD (CAD/CKD group, n=77). Plasma granzyme B was measured by enzyme-linked immunosorbent assay. Factors contributing to the severity of CAD were analyzed by multiple regression analysis in patients with CAD.
Plasma levels of high-sensitivity CRP (hs-CRP) and granzyme B in the CAD/CKD group were significantly higher than in other groups. A significant positive correlation was observed between plasma hs-CRP and granzyme B levels. A significant negative correlation was observed between eGFR and granzyme B levels. Multiple regression analysis revealed that granzyme B and hs-CRP levels were independent predicting variables of the number of stenoses in major coronary arteries.
These results indicate that granzyme B might be a novel risk factor for the formation of coronary atherosclerosis by inducing apoptosis of vascular tissues in patients with CKD.
Journal of Cardiology 12/2009; 54(3):409-15. · 1.28 Impact Factor
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Hideyuki Kondo,
Yukihiro Hojo,
Rie Tsuru,
Yoshioki Nishimura,
Hayato Shimizu,
Nozomu Takahashi,
Masahiro Hirose, Tomokazu Ikemoto,
Ken-Ichi Ohya,
Takaaki Katsuki,
Takashi Yashiro,
Kazuyuki Shimada
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ABSTRACT: Apoptosis is reported to play an important role in left ventricular (LV) remodeling after acute myocardial infarction (AMI). Granzyme B is a member of the serine esterase family, which has an important role in cellular apoptosis and extracellular matrix degradation.
Peripheral blood samples were obtained from 33 patients with a first-onset AMI treated by percutaneous coronary intervention (mean age: 61.4+/-8.7 years old) on days 1, 7 and 14 after onset. Plasma levels of tumor necrosis factor (TNF)-alpha, a soluble form of the Fas ligand (sFasL), and granzyme B were measured. TIMI grade 3 recanalization was accomplished in all patients within 12 h after onset. The LV end-diastolic volume index (LVEDVI) was calculated on day 1 and at 6 months after onset. Plasma levels of TNF-alpha, sFasL and granzyme B increased significantly on days 7 and 14 after onset of AMI. Stepwise multivariate regression analysis showed that the plasma granzyme B level on day 14 is a significant explanatory variable for changes in the LVEDVI.
Plasma levels of granzyme B increased after AMI, which might be an important factor in the progression of late LV remodeling after AMI.
Circulation Journal 02/2009; 73(3):503-7. · 3.77 Impact Factor
