Kenichi Sugioka

Erythrocyte-rich thrombus aspirated from patients with ST-elevation myocardial infarction: association with oxidative stress and its impact on myocardial reperfusion

AIMS Recent studies have demonstrated that erythrocytes are a potential component in atheromatous lesions and thrombus formation in patients with ST-elevation myocardial infarction (STEMI). The purpose of this study was to determine the associations of red blood cell (RBC) component of coronary thrombi with oxidative stress and myocardial reperfusion. METHODS AND RESULTS Aspirated thrombi from 178 STEMI patients within 12 h of symptom onset were investigated immunohistochemically using antibodies against platelets, RBCs, fibrin, macrophages, and neutrophils [myeloperoxidase (MPO)]. The thrombi were divided into tertiles according to the percentage of glycophorin-A-positive area: low (glycophorin-A-positive area <33%; n = 60), intermediate (<54 to 33%; n = 59), and high group (≥54%; n = 59). We also measured plasma MPO levels on admission. In the thrombi, the number of MPO-positive cells in the high-RBC group was significantly greater than that in the low-RBC group (high, 927 ± 385; intermediate, 765 ± 406; low, 279 ± 220 cells/mm(2); P< 0.0001). Plasma MPO levels were significantly higher in the high-RBC group than that in the low-RBC group [low 43.1 (25.0-71.6); intermediate 71.0 (32.9-111.2); high 74.3 (31.1-126.4)ng/mL; P< 0.005]. Distal embolization occurred more frequently in the high-RBC group (P= 0.0009). Moreover, the signs of impaired myocardial reperfusion, as indicated by incomplete ST-segment resolution (STR) and lower myocardial blush grades (MBG), and progression of left ventricular remodelling at 6 months were frequently observed in the high-RBC group (high vs. low: STR, P= 0.056; MBG, P< 0.01; remodelling, P< 0.01). CONCLUSION The present study demonstrated that erythrocyte-rich thrombi contain more inflammatory cells and reflect high thrombus burden, leading to impaired myocardial reperfusion in STEMI patients.

Automated Assessment of Left Atrial Function From Time-Left Atrial Volume Curves Using a Novel Speckle Tracking Imaging Method

BACKGROUND Using a novel speckle-tracking imaging method, time-left atrial (LA) volume curves (TLAVCs) can be automatically obtained. The aim of this study was to evaluate whether this method can be used for the measurement of LA function with TLAVCs. METHODS In 10 normal subjects and 20 patients, apical 4-chamber images were obtained. Maximum volume, reservoir volume, conduit volume, booster pump volume, and minimum volume were measured from TLAVCs. The results were compared with those obtained by the manual tracing method on every frame during 1 cardiac cycle. RESULTS There was good agreement between the speckle-tracking imaging and manual methods for maximum LA volume (r = 0.98, P < .001), reservoir volume (r = 0.82, P < .001), conduit volume (r = 0.87, P < .001), booster pump volume (r = 0.80, P < .001), and minimum volume (r = 0.98, P < .001). The time to obtain TLAVCs was significantly shorter with the speckle-tracking imaging method (64 +/- 22 seconds) than with the manual method (22 +/- 4 minutes). CONCLUSION TLAVCs obtained using the speckle-tracking imaging method can be used for the rapid and noninvasive automated quantitation of LA function.

Elevated levels of neopterin are associated with carotid plaques with complex morphology in patients with stable angina pectoris

OBJECTIVE Neopterin is an activation marker for monocytes/macrophages, and circulating levels of neopterin are elevated in patients with coronary complex lesions in unstable angina pectoris. We investigated the possible association between neopterin and complex carotid plaques which may be associated with the risk of ischemic stroke in patients with stable angina pectoris (SAP). METHODS We measured plasma levels of neopterin in 102 patients with SAP and carotid ultrasound was performed for evaluation of the presence of carotid plaques and plaque surface characteristics categorized as complex or noncomplex. In addition, endarterectomy specimens of extracranial high-grade carotid stenosis with complex plaques from five patients with SAP were immunohistochemically examined with antibodies to smooth muscle cells, endothelial cells, platelets, macrophages, and T cells. RESULTS Plasma neopterin levels were significantly higher in patients with complex carotid plaques than in those with noncomplex plaques (median [interquartile range]: 24.2 [19.2-39.3]nmol/L vs. 19.4 [11.9-25.1]nmol/L; P=0.01) or without any plaques (18.8 [14.9-23.6]nmol/L; P=0.001). On multivariate logistic analyses after adjustment for traditional atherosclerotic risk factors, multi-vessel coronary disease and high sensitivity C-reactive protein, neopterin levels were independently associated with the presence of complex carotid plaques (adjusted OR 2.21 per SD increase, 95%CI 1.13-4.33, P=0.02). Immunohistochemical staining revealed abundant neopterin-positive macrophages in carotid complex lesions. CONCLUSION These findings demonstrate that carotid plaques with complex morphology have increased circulating neopterin levels and immunohistochemical localization of neopterin in patients with SAP. Neopterin can be considered an important biomarker of plaque destabilization in carotid artery atherosclerotic lesions in this population.

Relationship of Thrombus Characteristics to the Incidence of Angiographically Visible Distal Embolization in Patients With ST-Segment Elevation Myocardial Infarction Treated With Thrombus Aspiration

OBJECTIVES This study sought to investigate the association between pathological characteristics of aspirated intracoronary thrombi and the incidence of angiographically visible distal embolization (AVDE) during primary percutaneous coronary intervention (p-PCI) in patients with ST-segment elevation myocardial infarction (STEMI) treated with thrombus aspiration. BACKGROUND AVDE of atherosclerotic and thrombotic material has been shown to impair myocardial perfusion and contribute to poor clinical outcome in patients with STEMI. Recent studies have shown that thrombus composition and size are associated with the incidence of AVDE. METHODS Aspirated thrombi from 164 STEMI patients within 12 h of symptom onset were investigated immunohistochemically using antibodies against platelets, erythrocytes, and inflammatory cells. RESULTS The angiographic results showed that AVDE during p-PCI occurred in 22 (13.4%) patients. Pathological analysis revealed that thrombi from patients with AVDE had a greater erythrocyte-positive area (60 ± 15% vs. 43 ± 21%, p < 0.0005) and more myeloperoxidase-positive cells (943 ± 324 cells/mm(2) vs. 592 ± 419 cells/mm(2), p < 0.0005) than those from patients without AVDE. Thrombus size, quantified as the thrombus surface area, was positively correlated with the erythrocyte component (r = 0.362, p < 0.0001). Moreover, multivariate logistic analysis demonstrated that erythrocyte-positive area in the thrombi, glucose levels on admission, larger vessel diameter (≥ 3.5 mm), and pre-balloon dilation were independent predictors of the incidence of AVDE. CONCLUSIONS This study demonstrated that the erythrocyte-rich component of aspirated thrombi may be associated with the incidence of AVDE during p-PCI in patients with STEMI.

Arachidonic acid and docosahexaenoic acid supplementation increases coronary flow velocity reserve in Japanese elderly individuals

Background: Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important components of phospholipids and cell membranes. There has, however, been no clinical report on the direct effects of ARA and DHA on coronary circulation. Objective: To evaluate the effects of ARA and DHA on coronary circulation using the measurement of coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography (TTDE). Methods: A double-blind, placebo-matched study of 28 Japanese elderly individuals (19 men, mean age 65 years) conducted to compare the effects of polyunsaturated fatty acids (PUFA; ARA 240 mg/day, DHA 240 mg/day) and placebo on CFVR. Coronary flow velocity (CFV) of the left anterior descending coronary artery was measured at rest and during hyperaemia by TTDE to determine CFVR. Results: There were no significant differences in CFV at rest or during hyperaemia in CFVR at baseline in the two groups (PUFA versus placebo 17 (7 SD) versus 16 (6), 62 (20) versus 59 (12), and 3.85 (1.04) versus 3.98 (0.83) cm/s, respectively). After three months’ supplementation, CFV during hyperaemia was significantly higher in the PUFA than in the placebo group (73 (19) versus 64 (12) cm/s, p<0.01) although no significant difference was found between the two groups in CFV at rest (17 (7) versus 16 (4) cm/s). CFVR thus significantly increased after PUFA consumption (3.85 (1.04) versus 4.46 (0.95), p = 0.0023). Conclusion: Three months’ supplementation of PUFA increased CFVR in Japanese elderly individuals, which suggests beneficial effects of PUFA on the coronary microcirculation.

Relation of Elevated Levels of Plasma Myeloperoxidase to Impaired Myocardial Microcirculation After Reperfusion in Patients With Acute Myocardial Infarction

Previous studies have shown that oxidative stress and endothelial dysfunction are related to impaired myocardial microcirculation after reperfusion. Moreover, elevated myeloperoxidase (MPO) levels are associated with endothelial dysfunction. Plasma MPO levels were measured in patients with ST-segment elevation acute myocardial infarction (n = 160) who had undergone percutaneous coronary stenting within 12 hours of symptom onset. We investigated whether the plasma MPO level at admission was associated with impaired myocardial microcirculation, as indicated by ST-segment resolution and myocardial blush grade after reperfusion, and left ventricular ejection fraction and remodeling at 6 months. The patients were divided into 2 groups according to the median MPO value for the entire cohort (low-MPO group < or =50 ng/ml, n = 80; high-MPO group >50 ng/ml, n = 80). ST-segment resolution and the myocardial blush grade were significantly lower in the high-MPO than in the low-MPO group (48 +/- 27% vs 61 +/- 24%, p <0.005; and 2.1 +/- 0.8 vs 2.4 +/- 0.7, p <0.01; respectively). Moreover, the percentage of increase in the left ventricular end-diastolic volume index was significantly greater and the left ventricular ejection fraction at 6 months was significantly lower in the high-MPO group than in the low-MPO group (8.2 +/- 24.7% vs -1.9 +/- 23.5%, p <0.05; and 46 +/- 9% vs 54 +/- 9%, p <0.0001, respectively). Multiple regression analysis showed that the plasma MPO level was an independent predictor of incomplete ST-segment resolution (odds ratio 6.94, 95% confidence interval 2.10 to 22.9, p = 0.0015). In conclusion, elevated plasma MPO levels at admission were associated with impaired myocardial microcirculation after reperfusion in patients with acute myocardial infarction.

Beneficial effect of short term intake of red wine polyphenols on coronary microcirculation in patients with coronary artery disease

Previous studies have shown the antioxidant effects of polyphenols in red wine.1–4 An acute effect of red wine on the coronary microcirculation has been shown in healthy volunteers, although neither white wine nor vodka had an acute effect on coronary microcirculation in that study.5 Thus, we hypothesised that the coronary microcirculation can be improved by a daily intake of red wine polyphenols without alcohol. In addition, this effect may be seen not only in the healthy person but also in the patient with coronary artery disease (CAD). Recent advances in transthoracic Doppler echocardiography (TTDE) have enabled non-invasive assessment of coronary flow velocity reserve (CFVR) in the clinical setting.6,7 This non-invasive technique has made serial assessment of CFVR after daily intake of red wine polyphenols possible even in patients with CAD. The purpose of this study was to evaluate the short term effect of taking red wine polyphenols on the coronary microcirculation by using TTDE to assess patients with CAD. Ten male patients with angiographically documented CAD were recruited for this study (mean (SD) age 61 (7) years, body mass index 28.5 (5.2) kg/cm2) in New York, USA and Osaka, Japan from October 2000 to March 2002. Exclusion criteria were as follows: (1) anterior myocardial infarction (MI); (2) significant stenosis (> 50%) in the left anterior descending coronary artery; (3) recent MI (< 6 months); (4) severely disturbed cardiac function (ejection fraction < 40%); (5) uncontrolled hypertension (systolic …

Relation of Aortic Arch Complex Plaques to Risk of Cerebral Infarction in Patients With Aortic Stenosis

Aortic stenosis (AS) and systemic atherosclerosis have been shown to be closely related. We evaluated the prevalence of aortic arch plaques and their possible association with the risk of cerebral infarction in patients with severe AS. Transesophageal echocardiography was performed in 116 patients with severe AS (55 men, mean age 71 ± 7 years, mean aortic valve area 0.68 ± 0.15 cm(2)) who were scheduled for aortic valve replacement. The presence, thickness, and morphology of the aortic arch plaques were evaluated using transesophageal echocardiography. Cerebral infarcts (chronic cerebral infarction and cerebral infarction after cardiac catheterization and aortic valve replacement) were assessed in all patients. Compared to age- and gender-matched control subjects, the patients with severe AS had a significantly greater prevalence of aortic arch plaques (74% vs 41%; p <0.0001) and complex arch plaques such as large plaques (≥4 mm), ulcerated plaques, or mobile plaques (30% vs 10%; p = 0.004). Multivariate logistic analyses showed that the presence of complex arch plaques was independently associated with cerebral infarction in patients with AS after adjusting for traditional atherosclerotic risk factors and coronary artery disease (odds ratio 8.46, 95% confidence interval 2.38 to 30.12; p = 0.001). In conclusion, the results from the present study showed that there is a greater prevalence of aortic arch plaques in patients with AS and that the presence of complex plaques is independently associated with cerebral infarction in these patients. Therefore, the identification of complex arch plaques using transesophageal echocardiography is important for risk stratification of cerebrovascular events in patients with severe AS.

Comparison of determinations of left atrial volume by the biplane area-length and Simpson's methods using 64-slice computed tomography

OBJECTIVES There is increasing evidence that left atrial (LA) size is an important predictor of adverse cardiovascular outcomes such as atrial fibrillation, stroke, and congestive heart failure. The aim of this study was to determine whether there is a difference in results of quantification of LA volume by the area-length and Simpsons methods using multislice computed tomography (MSCT). METHODS AND RESULTS The study population consisted of 51 patients with sinus rhythm (sinus group) and 20 patients with atrial fibrillation (af group) clinically indicated for MSCT angiography for evaluation of coronary arteries. Maximum LA volume, obtained at end-systole from the phase immediately preceding mitral valve opening, was measured using the area-length and Simpsons methods. In the sinus group, the mean LA volumes, indexed to body surface area, were 48.4+/-17.9 ml/m(2) with the area-length method and 48.3+/-17.0 ml/m(2) with the Simpsons method. In the af group, the mean indexed LA volumes with the area-length method and the Simposons method were 91.5+/-47.5 ml/m(2) and 90.3+/-45.9 ml/m(2), respectively. LA volumes calculated by the area-length method exhibited a strong linear relationship and agreement with those calculated using Simpsons method in both the groups (sinus group: r=0.99, P<0.0001, af group: r=0.99, P<0.0001). CONCLUSIONS The area-length method is a simple and reproducible means of assessment of LA volume. Standardization of LA volume assessment using MSCT is important for serial follow-up and meaningful communication of results of testing among institutions and physicians.

Usefulness of three-dimensional automated quantification of left ventricular mass, volume, and function by 64-slice computed tomography.

OBJECTIVES Quantification of left ventricular (LV) mass has important prognostic implications. However, accurate measurement of LV mass has been difficult, in part because of the oblique angle at which the heart lies within the chest and the continuous movement of the heart itself. Multislice computed tomography (MSCT) allows assessment not only of coronary stenosis but LV volume, function, and mass. A novel three-dimensional (3D) region-growing-based semi-automated segmentation algorithm for measurements of LV mass, volume, and function was recently developed. This study evaluated this new 3D automated method for measurement of LV mass, by comparison with a well-established 2D manual contour-drawing algorithm. METHODS AND RESULTS The study population consisted of 50 consecutive patients who underwent ECG-gated MSCT for evaluation of coronary arteries. The 3D algorithm for reliable segmentation was unsuccessful in two patients. In the remaining 48 patients, however, LV segmentation using this algorithm was performed and delivered visually reliable segmentation results. The 3D algorithm for analysis of LV function and mass is feasible based on volumetric data, and exhibits good correlation and agreement with the results obtained with the conventional 2D algorithm. The time required for the new automated algorithm was significantly shorter than that for the manual contour-drawing algorithm (P<0.0001) (automated algorithm: 468.0±205.1 s, manual algorithm: 1362.4±410.5 s, mean ±S.D.). CONCLUSIONS The 3D semi-automated region-growing segmentation algorithm for analysis of LV function and mass is feasible based on volumetric data, and exhibits good correlations and agreement with the results of the conventional 2D manual contour-drawing algorithm.