Michihiko Kitayama

Increased levels of the oxidative stress marker, nitrotyrosine in patients with provocation test-induced coronary vasospasm

BACKGROUND Endothelial dysfunction of the coronary arteries caused by oxidative stress plays an important role in the pathogenesis of coronary vasospasm. However, it is not clear whether circulating biomarkers for oxidative stress are altered after coronary vasospasm. We investigated temporal changes in the levels of oxidative stress biomarkers after coronary vasospasm induced by intracoronary acetylcholine provocation testing, resulting in transient myocardial ischemia. METHODS AND RESULTS Thirty consecutive patients with suspected vasospastic angina pectoris (VSAP) were enrolled in the study. Patients were categorized into the VSAP-positive group (n=14) and the VSAP-negative group (n=16) on the basis of test results. Serum samples were examined for the levels of the oxidative stress markers 4-hydroxynonenal (HNE) and nitrotyrosine (NT) before, and 15min, 3h, and 12h after the provocation test. The serum HNE levels did not change in either group after the test. The serum NT levels in the VSAP-positive group significantly increased at 3h and 12h after the test (11.3±3.3μg/ml at 3h, p=0.015, and 12.1±5.7μg/ml at 12h, p=0.03), as compared with baseline (8.1±3.2μg/ml). In the VSAP-negative group, the serum NT levels significantly decreased from baseline at each of the 3 time points. CONCLUSIONS Serum NT significantly increased after coronary vasospasm induced by acetylcholine provocation, suggesting that serum NT could be a biomarker of transient myocardial ischemia and could contribute to the development of VSAP.

Levels of serum deoxyribonuclease I activity on admission in patients with acute myocardial infarction can be useful in predicting left ventricular enlargement due to remodeling

OBJECTIVES Serum deoxyribonuclease I (DNase I) activity has recently been highlighted as a potential diagnostic marker for the early detection of an acute myocardial infarction (AMI). We evaluated whether the serum DNase I activity was associated with the parameters of the left ventricular (LV) remodeling after an AMI. METHODS We measured the serum DNase I activity in 45 patients with an AMI who were admitted to our hospital within approximately 4 h of the onset of their chest pain. We also evaluated the LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV) of each patient by echocardiography at the time of admission and at 6 months after the onset of the AMI. RESULTS The serum DNase I activity peaked at 3.5+/-2.0 h after the onset of the symptoms in the patients with an AMI, thereafter exhibiting a time-dependent decline within 12 h, and a return to the basal level within 24 h in almost all cases. Neither the LVEF, LVEDV, nor LVESV in each patient on admission exhibited a significant correlation to the peak levels of the serum DNase I activity. Although there was no correlation between the peak DNase I activity and LVEF at 6 months after the onset, a significant positive correlation of the peak DNase I activity with LVEDV and LVESV (r=0.48, p<0.001 and r=0.34, p=0.02, respectively) was found. Furthermore, the LVEDV at 6 months after the onset in the high DNase I activity group (> 17.9 U/L) were significantly higher than those in the low DNase I activity group (< or = 17.9 U/L) (118.0+/-28.2 ml vs 89.3+/-25.4 ml, p=0.026). CONCLUSIONS The serum DNase I activity level may predict LV enlargement associated with remodeling after an AMI.

A quantitative coronary angiography-matched comparison between a prospective randomised multicentre cutting balloon angioplasty and bare metal stent trial (REDUCE III) and the Rapamycin-Eluting Stent Evaluation at Rotterdam Cardiology Hospital (RESEARCH) study

AIMS There remains significant concern about the long-term safety of drug-eluting stents (DES). However, bare metal stents (BMS) have been used safely for over two decades. There is therefore a pressing need to explore alternative strategies for reducing restenosis with BMS. This study was designed to examine whether IVUS-guided cutting balloon angioplasty (CBA) with BMS could convey similar restenosis rates to DES. METHODS AND RESULTS In the randomised REstenosis reDUction by Cutting balloon angioplasty Evaluation (REDUCE III) study, 521 patients were divided into four groups based on device and IVUS use before BMS (IVUS-CBA-BMS: 137 patients; Angio-CBA-BMS: 123; IVUS-BA-BMS: 142; and Angio-BA-BMS: 119). At follow-up, the IVUS-CBA-BMS group had a significantly lower restenosis rate (6.6%) than the other groups (p=0.016). We performed a quantitative coronary angiography (QCA) based matched comparison between an IVUS-guided CBA-BMS strategy (REDUCE III) and a DES strategy (Rapamycin-Eluting-Stent Evaluation At Rotterdam Cardiology Hospital, the RESEARCH study). We matched the presence of diabetes, vessel size, and lesion severity by QCA. Restenosis (>50% diameter stenosis at follow-up) and target vessel revascularisation (TVR) were examined. QCA-matched comparison resulted in 120-paired lesions. While acute gain was significantly greater in IVUS-CBA-BMS than DES (1.65±0.41 mm vs. 1.28±0.57 mm, p=0.001), late loss was significantly less with DES than with IVUS-CBA-BMS (0.03±0.42 mm vs. 0.80±0.47 mm, p=0.001). However, no difference was found in restenosis rates (IVUS-CBA-BMS: 6.6% vs. DES: 5.0%, p=0.582) and TVR (6.6% and 6.6%, respectively). CONCLUSIONS An IVUS-guided CBA-BMS strategy yielded restenosis rates similar to those achieved by DES and provided an effective alternative to the use of DES.

Serum deoxyribonuclease I activity can be a useful diagnostic marker for the early diagnosis of unstable angina pectoris or non–ST-segment elevation myocardial infarction

BACKGROUND AND PURPOSE Recently, serum deoxyribonuclease I (DNase I) activity has been highlighted as a potential diagnostic marker for transient myocardial ischemia. To evaluate whether serum DNase I activity can be a useful biomarker for diagnosing unstable angina pectoris (UAP) or non-ST-segment elevation myocardial infarction (NSTEMI), we investigated serial changes in DNase I levels after chest pain in UAP and NSTEMI (UAP/NSTEMI) patients. METHODS AND RESULTS Thirty-three and ten patients classified into the UAP/NSTEMI and the chest pain syndrome (CPS) group, respectively, were enrolled. The serum DNase I activity levels within 3h after chest pain and the absolute median value of percentage differences in serum DNase I activity levels from admission to 3h after hospitalization in the UAP/NSTEMI patients was significantly higher than those in the CPS patients. We evaluated the patients to show positive results for DNase I activity if the serum levels or percentage differences exceeded the corresponding cut-off values. The sensitivity and specificity of DNase I within 6h after chest pain in the UAP/NSTEMI patients without elevated levels of cardiac troponin T and the MB isoenzyme of creatine kinase were 89% and 88%, respectively. CONCLUSIONS Serum DNase I activity can be a useful marker for the early diagnosis of UAP/NSTEMI after the onset of chest pain, irrespective of the evidence of myocardial injury.

Diurnal glycemic fluctuation is associated with severity of coronary artery disease in prediabetic patients: Possible role of nitrotyrosine and glyceraldehyde-derived advanced glycation end products.

BACKGROUND Glucose fluctuation (GF) is a risk factor for coronary artery disease (CAD). However, it remains unknown whether specific indices of GF are risk factors for CAD. Therefore, we evaluated the relationship between GF, as determined by a continuous glucose monitoring system (CGMS) or the glucose level at 2h after a 75-g oral glucose tolerance test (75g OGTT 120), and the severity of CAD in prediabetic patients. We also evaluated whether nitrotyrosine (NT) and glyceraldehyde-derived advanced glycation end-products (Glycer-AGE) were induced by GF. METHODS Twenty-eight prediabetic patients underwent coronary angiography (CAG), and the Gensini score and the SYNTAX score were evaluated as the severity of CAD, while the mean amplitude of glycemic excursions (MAGE) by CGMS and 75g OGTT 120 were evaluated. Serum NT and Glycer-AGE were measured. RESULTS The MAGE was closely associated with the Gensini score (r=0.742, p<0.001) and the SYNTAX score (r=0.776, p<0.001), respectively. The 75g OGTT 120 was not associated with the Gensini score (r=0.36, p=0.06), but it was significantly associated with the SYNTAX score (r=0.413, p=0.036). Multiple linear regression analysis showed that the MAGE was the only independent determinant for the severity of CAD. The levels of NT and Glycer-AGE were significantly higher in the high MAGE group than in the low MAGE group. CONCLUSIONS Diurnal GF is associated with the severity of CAD, even in prediabetic patients. GF, NT, and Glycer-AGE may play a pathological role in the progression of CAD.

A case of coronary rupture and pseudoaneurysm formation after fracture of implanted paclitaxel-eluting stents

A 48-year-old man who had undergone implantation of two paclitaxel-eluting stents (PESs) at the right coronary artery was admitted to our hospital with progressive dyspnea. In the coronary care unit, he developed cardiogenic shock due to cardiac tamponade treated by pericardiocentesis. A coronary angiogram showed a large pseudoaneurysm at the site of the previously implanted stents, suggesting coronary rupture due to implanted stent fracture. The pseudoaneurysm was completely sealed by polytetrafluoroethylene-covered stent implantation. Although this case is very rare, coronary rupture by stent fracture should be considered when cardiac tamponade occurs after drug-eluting stent implantation, especially PES.

Clinical characteristics of patients with Rutherford category IV, compared with V and VI.

Objective: Patients categorized Rutherford category IV might have different characteristics compared with Rutherford category V and VI. Our study aims were to estimate the clinical differences between Rutherford category IV and Rutherford category V and VI, for those underwent endovascular therapy for isolated infrapopliteal disease, and also to find risk factors for endovascular therapy in Rutherford category IV. Methods: Based on the Japanese multi-center registry data, 1091 patients with 1332 limbs (Rutherford category IV: 226 patients with 315 limbs, Rutherford category V and VI: 865 patients with 1017 limbs) were analyzed retrospectively. Results: Patients’ backgrounds and lesions’ characteristics had significant differences. Both freedom rate from major adverse limb event with perioperative death and amputation-free survival rate at 1 year were better in Rutherford category IV than Rutherford category V and VI (93.6% vs 78.3%, 87.7% vs 66.7%) and those maintained to 3 years (p < 0.0001). Significant predictors for major adverse limb event/perioperative death were small body mass index (<18.5 kg/m3) and initial endovascular therapy success, and those for amputation-free survival were small body mass index (<18.5 kg/m3), non-ambulatory status, high systematic inflammatory reaction (C-reactive protein > 3.0 mg/dL), chronic obstructive pulmonary disease, and coronary artery disease in Rutherford category IV. Conclusion: From the present results, Rutherford category IV should be recognized to have quite different backgrounds and better outcome from Rutherford category V and VI.

Clinical impact and risk stratification of balloon angioplasty for femoropopliteal disease in nitinol stenting era: Retrospective multicenter study using propensity score matching analysis

Objective: Nitinol stenting could bring the better outcome in endovascular therapy for femoropopliteal disease. However, it might be expected that recent marked advances in both device technology and operator technique had led to improved efficacy of balloon angioplasty even in this segment. The aims of this study were to evaluate the clinical impact of balloon angioplasty for femoropopliteal disease and make risk stratification clear by propensity score matching analysis. Methods: Based on the multicenter retrospective data, 2758 patients (balloon angioplasty: 729 patients and nitinol stenting: 2029 patients), those who underwent endovascular therapy for femoropopliteal disease, were analyzed. Results: The propensity score matching procedure extracted a total of 572 cases per group, and the primary patency rate of balloon angioplasty and nitinol stenting groups after matching was significantly the same (77.2% vs 82.7% at 1 year; 62.2% vs 64.3% at 3 years; 47.8% vs 54.3% at 5 years). In multivariate Cox hazard regression analysis, significant predictors for primary patency were diabetes mellitus, regular dialysis, cilostazol use, chronic total occlusion, and intra-vascular ultra-sonography use. The strategy of balloon angioplasty was not evaluated as a significant predictor for the primary patency. After risk stratification using five items (diabetes mellitus, regular dialysis, no use of intra-vascular ultra-sonography, chronic total occlusion, and no use of cilostazol: the DDICC score), the estimated primary patency rates of each group (low, DDICC score 0–2; moderate, DDICC score 3; high risk, DDICC score 4–5) were 88.6%, 78.3%, and 63.5% at 1 year; 75.2%, 60.7%, and 39.8% at 3 years; and 66.0%, 47.1%, and 26.3% at 5 years (p < 0.0001). The primary patency rate of balloon angioplasty and nitinol stenting groups was significantly the same in each risk stratification. Conclusion: This study suggests that balloon angioplasty does not have inferiority to nitinol stenting but does have favorable efficacy in femoropopliteal segment by careful risk stratification with the recent advance of technique.

Chronic total occlusions of the right coronary and left anterior descending coronary arteries in a young adult patient with antiphospholipid syndrome

A 36-year-old male appeared to have an old myocardial infarction on electrocardiogram, and coronary angiography (CAG) was performed. The CAG showed total occlusions of the right coronary artery and left anterior descending artery. He was successfully treated with drug-eluting stent implantation for both occluded coronary arteries. Such serious coronary lesions are uncommon for his young age. The patient was diagnosed as having antiphospholipid syndrome (APS) based on elevation of anticardiolipin antibody and anti-β2 glycoprotein I antibody. Two years after stent implantation, the patient was well without ischemia or thrombosis. APS should be considered a potential cause of serious coronary disease in young adults. <Learning objective: Antiphospholipid syndrome (APS) should be considered a potential cause of serious coronary disease in young adults. Although there is a high risk of acute stent thrombosis and restenosis after multiple stents implantation, percutaneous coronary intervention with drug-eluting stent implantation could be an appropriate therapy for chronic total occlusion in APS patients.>.

Case report: unstable angina with flow-fatty acid metabolism mismatch and reverse flow-glucose metabolism mismatch patterns.

A 79-year-old man with unstable angina underwent an emergency coronary angiography, and percutaneous balloon angioplasty was performed for LCX. Left ventriculography showed hypokinesis in the posterior wall, inferior and apical wall immediately after the PCI therapy. The defects on123I-BMIPP SPECT seen in the inferior, posterior and lateral wall were more extensive than those observed on99mTc-MIBI SPECT, and a flow-fatty acid metabolism mismatch pattern was observed. The18F-FDG PET showed reduced uptake in the lateral segment, although13N-NH3 PET showed normal perfusion, and a reverse flow-glucose metabolism mismatch pattern was observed. Left ventriculography showed significant improve to normal contraction on the 3-month follow up, and there was not significantly reduced uptake in99mTc-MIBI SPECT,123I-BMIPP SPECT,13N-NH3 PET or18F-FDG PET.