Prognostic Value of Human Peripheral Monocyte Subsets for Future Coronary Events in Patients Without Significant Coronary Artery Stenosis.

BACKGROUND: Monocytes in human peripheral blood are heterogeneous and can be divided into 2 groups, inflammatory and pro-inflammatory, according to the differential expression of CD14 and CD16. Pro-inflammatory monocytes (CD14+CD16+) seem to contribute to the development of coronary artery disease. This study aimed to investigate the involvement of specific human peripheral monocyte subsets in the development of future coronary events.Methods and Results:We enrolled 271 patients who were suspected to have either stable angina pectoris or silent myocardial ischemia and underwent coronary angiography (CAG). Two monocyte subsets (CD14+CD16-and CD14+CD16+) were measured by flow cytometry. Patients who did not undergo coronary artery revascularization at initial CAG were followed as the medical therapy group, which included 136 patients among whom 15 had future coronary events. The frequency of CD14+CD16+monocytes was significantly higher in patients who had future coronary events than in those who did not (P<0.01). Furthermore, the frequencies of CD14+CD16+monocyte were not significantly different between patients who had future coronary events and those who underwent coronary revascularization at initial CAG (P<0.33). Multivariate analysis revealed that the frequency of CD14+CD16+monocytes was an independent predictor for future coronary events (P<0.01). CONCLUSIONS: An increase in the abundance of human peripheral pro-inflammatory monocytes is related to the development of future coronary events.

Association of Toll-Like Receptor 4 on Human Monocyte Subsets and Vulnerability Characteristics of Coronary Plaque as Assessed by 64-Slice Multidetector Computed Tomography.

BACKGROUND: Although Toll-like receptor 4 (TLR-4) is involved in monocyte activation in patients with accelerated forms of atherosclerosis, the relationship between the expression of TLR-4 on circulating monocytes and coronary plaque vulnerability has not previously been evaluated. We investigated this relationship using 64-slice multidetector computed tomography (MDCT) in patients with stable angina pectoris (SAP).Methods and Results:We enrolled 65 patients with SAP who underwent MDCT. Three monocyte subsets (CD14++CD16-, CD14++CD16+, and CD14+CD16+) and expression of TLR-4 were measured by flow cytometry. Intracoronary plaques were assessed by 64-slice MDCT. We defined vulnerability of intracoronary plaques according to the presence of positive remodeling (remodeling index >1.05) and/or low CT attenuation (<35 HU). The circulating CD14++CD16+monocytes more frequently expressed TLR-4 than CD14++CD16-and CD14+CD16+monocytes (P<0.001). The relative proportion of the expression of TLR-4 on CD14++CD16+monocytes was significantly greater in patients with vulnerable plaque compared with those without (10.4 [4.1-14.5] % vs. 4.5 [2.8-7.8] %, P=0.012). In addition, the relative proportion of TLR-4 expression on CD14++CD16+monocytes positively correlated with the remodeling index (r=0.28, P=0.025) and negatively correlated with CT attenuation value (r=-0.31, P=0.013). CONCLUSIONS: Upregulation of TLR-4 on CD14++CD16+monocytes might be associated with coronary plaque vulnerability in patients with SAP.

Circulating CD14++CD16+ Monocyte Subsets as a Surrogate Marker of the Therapeutic Effect of Corticosteroid Therapy in Patients With Cardiac Sarcoidosis.

BACKGROUND: We aimed to evaluate whether specific monocyte subsets could serve as surrogate markers of disease activity in cardiac sarcoidosis (CS) evaluated by 18F-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET). METHODS AND RESULTS: We studied 28 patients with CS (8 men; mean age: 61±9 years) diagnosed according to consensus criteria. We divided the patients into 2 groups: known CS receiving corticosteroid therapy (Rx(+); n=13) and new-onset CS (Rx(-); n=15), and analyzed 3 distinct monocyte subsets (CD14+CD16-, CD14++CD16+, and CD14+ -CD16+). Monocyte subsets were also analyzed in 10 Rx(-) patients before and 12 weeks after starting corticosteroid therapy. Inflammatory activity was quantified by 18F-FDG PET using the coefficient of variation (COV) of the standardized uptake value (SUV). The proportion of CD14++CD16+ monocytes in Rx(+) patients (10.8 [0.2-23.5] %) was significantly lower than in Rx(-) patients (23.0 [11.5-38.4] %, P=0.001). After corticosteroid therapy, the COV of the SUV was significantly improved from 0.32 [0.14-0.62] to 0.17 [0.04-0.43] (P=0.017). The proportion of CD14++16+ monocytes showed a significant decrease from 22.2 [8.8-38.4] % to 8.4 [1.8-16.8] % (P=0.001). The decrease in the proportion of CD14++16+ monocytes significantly correlated with the decrease in the COV of the SUV (r=0.495, P=0.027). CONCLUSIONS: CD14++16+ monocytes are a possible surrogate marker of the therapeutic effect of corticosteroid therapy in CS.

Long-term outcome after deferral of revascularization in patients with intermediate coronary stenosis and gray-zone fractional flow reserve.

BACKGROUND: A strategy of deferred percutaneous coronary intervention for coronary stenosis with fractional flow reserve (FFR) 0.75-0.80, termed the gray zone, remains a matter of debate. The aim of this study was to assess the safety of deferring revascularization for patients with FFR 0.75-0.80 compared with those with FFR >0.80. METHODS AND RESULTS: We assessed 3-year clinical outcome in 150 patients with angiographically intermediate stenosis who had revascularization deferred on the basis of FFR ≥ 0.75 (FFR 0.75-0.80, n=56; FFR >0.80, n=94). Target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction (MI), and ischemia-driven target vessel revascularization (TVR) was evaluated during follow-up. Cardiac death was observed in 1 patient with FFR 0.75-0.80. There was no target vessel-related MI in either group. The incidence of ischemia-driven TVR was higher in patients with FFR 0.75-0.80 than in those with FFR >0.80 (14% vs. 3%, P=0.020). TVF-free survival was significantly worse for the patients with FFR 0.75-0.80 than those with FFR >0.80 (hazard ratio, 5.2; 95% confidence intervals: 1.4-19.5; P=0.015). CONCLUSIONS: Patients with FFR 0.75-0.80 were at higher risk of TVF mainly due to TVR than those with FFR >0.80.

Two-dimensional speckle tracking echocardiography for the prediction of reversible myocardial dysfunction after acute myocardial infarction: comparison with magnetic resonance imaging.

BACKGROUND: We aimed to determine the predictive value of longitudinal, circumferential, and radial strains by two-dimensional speckle tracking echocardiography (2DSTE) for improvement in cardiac function after acute myocardial infarction (AMI) compared with that of contrast-enhanced cardiac magnetic resonance imaging (ceMRI). METHODS: In 35 patients with first-time AMI, myocardial viability was assessed to predict recovery of function at follow-up (7 ± 2 months), prospectively. For each left ventricular segment, each peak strains were determined using 2DSTE, and the relative extent of hyperenhancement was assessed using ceMRI. RESULTS: Of 176 segments with impaired function early after AMI, 99 segments showed regional recovery. Compared with segments showing functional improvement, those that failed to recover had lower peak radial (20 ± 16% vs. 32 ± 21%; P < 0.001), circumferential (-10 ± 5% vs. -20 ± 6%; P < 0.001), and longitudinal (-10 ± 5% vs. -14 ± 5%; P < 0.001) strain and a greater extent of hyperenhancement (71 ± 22% vs. 27 ± 20%; P < 0.001). Among strain parameters, circumferential strain yielded greater area under the curve (AUC; 0.899) than radial and longitudinal strain (0.682 and 0.718, respectively). The predictive value of circumferential strain (sensitivity 81.0%, specificity 79.6%, at a cutoff value of -14.3%) could be comparable to that of hyperenhancement (sensitivity 86.2%, specificity 83.9%, AUC 0.921, at a cutoff value of 47%) (P = 0.439). CONCLUSION: Circumferential strain can identify reversible myocardial dysfunction after AMI with a diagnostic ability comparable to that of ceMRI.

Improvement of cardiac function by increasing stimulus strength during left ventricular pacing in cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is an established therapy in patients with severe heart failure due to left ventricular (LV) dyssynchrony. Increasing stimulus strength (SS) of LV pacing could capture an enlarged myocardial area and provide rapid electrical conduction. The aim of the present study was to investigate whether increasing SS of LV pacing improves LV mechanical dyssynchrony and cardiac function in patients treated with CRT.We enrolled 26 patients with CRT and changed the SS of LV pacing: 2.5 V (standard SS) and 5 V (high SS). Electrocardiography and echocardiography were performed to assess QRS duration, LV mechanical dyssynchrony, and cardiac function under each condition.The QRS duration (138.6 ± 21.4 ms versus 126.8 ± 23.1 ms, P < 0.001), septal-posterior wall motion delay (126.5 ± 42.7 ms versus 111.4 ± 55.3 ms, P = 0.012), standard deviation of time from QRS (69.6 ± 21.8 ms versus 55.6 ± 19.4 ms, P < 0.001), LV ejection fraction (29.4 ± 10.6% versus 33.4 ± 11.6%, P = 0.005), and LV stroke volume (50.7 ± 15.5 mL versus 63.8 ± 18.3 mL, P < 0.001) improved significantly in high SS compared with standard SS.Increasing SS of LV pacing in CRT improves LV mechanical dyssynchrony and cardiac function. The capture of an enlarged myocardial area by increasing SS of LV pacing might offer an acute hemodynamic benefit to patients treated with CRT.

Impact of low signal intensity assessed by cine magnetic resonance imaging on detection of poorly viable myocardium in patients with prior myocardial infarction.

Late gadolinium enhancement magnetic resonance imaging (LGE-MRI) has been established as a modality to detect myocardial infarction (MI). However, the use of gadolinium contrast is limited in patients with advanced renal dysfunction. Although the signal intensity (SI) of infarct area assessed by cine MRI is low in some patients with prior MI, the prevalence and clinical significance of low SI has not been evaluated. The aim of this study was to evaluate how low SI assessed by cine MRI may relate to the myocardial viability in patients with prior MI. Fifty patients with prior MI underwent both cine MRI and LGE-MRI. The left ventricle was divided into 17 segments. The presence of low SI and the wall motion score (WMS) of each segment were assessed by cine MRI. The transmural extent of infarction was evaluated by LGE-MRI. LGE was detected in 329 of all 850 segments (39%). The low SI assessed by cine MRI was detected in 105 of 329 segments with LGE (32%). All segments with low SI had LGE. Of all 329 segments with LGE, the segments with low SI showed greater transmural extent of infarction (78 [72 - 84] % versus 53 [38 - 72] %, P < 0.01), thinner wall (4.0[3.1 - 4.8] mm versus 6.5 [5.2 - 8.1] mm, P < 0.01), and higher WMS (4.0 [4.0 - 4.0] versus 2.0 [2.0 - 3.0], P < 0.01). The low SI assessed by cine MRI may be effective for detecting poorly viable myocardium in patients with prior MI.

Impact of myocardial supply area on the transstenotic hemodynamics as determined by fractional flow reserve.

OBJECTIVES: The aim of this study was to investigate the impact of myocardial area supplied by the coronary artery on fractional flow reserve (FFR). BACKGROUND: Various factors other than the degree of epicardial stenosis influence the physiological significance of a coronary artery stenosis. METHODS: A total of 296 coronary lesions in 217 patients were analyzed by quantitative coronary angiography and FFR. Myocardial area supplied by the coronary artery distal to the stenosis was evaluated by angiography using a modified version of the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) score. RESULTS: Percent diameter stenosis of the coronary lesion was 57 ± 15% (mean ± standard deviation). FFR <0.80 was seen in 132 (45%) lesions. FFR was significantly correlated with minimum lumen diameter (r = 0.584, P <0.001), percent diameter stenosis (r = -0.565, P <0.001), lesion length (r = -0.306, P <0.001), and myocardial supply area (r = -0.504, P <0.001). Multivariate logistic analysis demonstrated that minimum lumen diameter (odds ratio [OR] = 0.031, 95% confidence interval [CI] = 0.013-0.076, P < 0.001), lesion length (OR = 1.038, 95% CI = 1.009-1.069, P = 0.001), and myocardial supply area (OR = 1.113, 95% CI = 1.079-1.147, P <0.001) were independent determinants for FFR <0.80. CONCLUSIONS: FFR, which is the index of physiological significance of coronary artery stenosis, is influenced by myocardial supply area distal to the stenosis as well as by its own minimal lumen diameter and lesion length.

Acute-phase glucose fluctuation is negatively correlated with myocardial salvage after acute myocardial infarction.

BACKGROUND: It remains unclear whether glycemic fluctuation immediately after acute myocardial infarction (AMI) can affect myocardial damage. This study investigated the impact of glucose fluctuation on myocardial salvage following successful recanalization of primary AMI. METHODS AND RESULTS: A total of 36 consecutive patients with AMI were studied. Glycemic variability, as indicated by the mean amplitude of glycemic excursion (MAGE), was measured on a continuous glucose monitoring system. Three subsets (CD14(+)CD16(-), CD14(++)CD16(+) and CD14(+-)CD16(+)) were measured on flow cytometry 1, 2, 3, 4 and 5 days after AMI onset. A 2-h oral glucose test was performed in 23 patients who had no previous diagnosis of diabetes and/or glycated hemoglobin <6.5%, after the onset of AMI at 2 weeks. Plasma active glucagon-like peptide (GLP)-1 level was measured in each sample. The extent of myocardial salvage 7 days after AMI was evaluated on cardiovascular magnetic resonance imaging. MAGE and the peak CD14(+)CD16(-) monocyte level were significantly negatively correlated with myocardial salvage index (MSI). MAGE was significantly correlated with peak CD14(+)CD16(-) monocyte level. Of interest, plasma GLP-1 level was significantly positively correlated with MSI and significantly negatively correlated with MAGE. CONCLUSIONS: Glucose fluctuations during the acute phase of AMI affect MSI, indicating that manipulation of glucose variability from peak to nadir might be a potential therapeutic target for salvaging ischemic damage.

Assessment of circumferential endocardial extent of myocardial edema and infarction in patients with reperfused acute myocardial infarction: a cardiovascular magnetic resonance study.

T2 weighted (T2W) images on cardiovascular magnetic resonance (CMR) visualizes myocardial edema, which reflects the myocardial area at risk (AAR) in reperfused acute myocardial infarction (AMI). Late gadolinium enhancement (LGE) demonstrates myocardial infarction. LGE images cover the whole left ventricle, but T2W images are obtained from a few slices of the left ventricle due to the long sequence time, so the quantification of AAR of the entire left ventricle is difficult. We hypothesize that we can quantify AAR with only LGE images if there is a strong correlation between the circumferential endocardial extent of myocardial edema and infarction. Thirty patients with first AMI were enrolled. All patients underwent successfully reperfusion therapy and CMR was performed within the first week after the event. We measured the circumferential extent of edema and infarction on short-axis views (T2 angle and LGE angle), respectively. A total of 82 short-axis slices showed transmural edema on T2W images. Corresponding LGE images were analyzed for the circumferential extent of infarction. The median [interquartile range] of T2 angle and DE angle were 147° [116°-219°] and 134° [104°-200°] in patients with LAD culprit lesion, 91° [87°-101°] and 85° [80°-90°] in LCX, and 110° [94°-123°] and 104° [89°-118°] in RCA, respectively. T2 angle was well correlated with LGE angle (r = 0.99, P < 0.01). There is a strong correlation between the circumferential extent of edema and infarction in reperfused AMI. Thus, T2 weighted imaging can be skipped to quantify the amount of AAR.

Effect of direct renin inhibitor on left ventricular remodeling in patients with primary acute myocardial infarction.

Some patients with acute myocardial infarction (AMI) have a poor prognosis due to left ventricular remodeling (LVR), resulting in the recurrence of congestive heart failure even when therapy with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) has been initiated. We investigated the effect of early administration of the direct renin inhibitor (DRI) aliskiren in combination with an ACEI or an ARB on LVR using cardiac magnetic resonance (CMR) imaging in patients with AMI.Twenty-one consecutive patients were treated with an ACEI or an ARB (non-DRI group), and another 21 consecutive patients received aliskiren 150 mg/day combined with an ACEI or an ARB (DRI group). CMR imaging was performed 7 days after AMI and 10 months later.CMR imaging revealed no significant changes in LV end-systolic volume, LV end-diastolic volume, or LV ejection fraction between the patients with and without DRI aliskiren. In the DRI group, plasma renin activity was significantly lower in both the acute and chronic phases; however, aldosterone levels were significantly lower in the acute but not the chronic phase.A low dose of aliskiren may be insufficient to maintain suppression of aldosterone under current standard therapies with an ACEI or an ARB and ß-blocker in patients with primary AMI, and results in no attenuation of LVR.

High-density lipoprotein cholesterol level is associated with fibrous cap thickness in acute coronary syndrome.

BACKGROUND: Although low high-density lipoprotein cholesterol (HDL-C) level has been reported as an independent risk factor for coronary artery disease, few studies addressed the direct relationship between the presence of thin-cap fibroatheroma (TCFA) that is considered as vulnerable plaque in pathology and HDL-C level. The aim of this study was to investigate whether lesion vulnerability is related to HDL-C level in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: A total of 261 patients with ACS who underwent optical coherence tomography prior to percutaneous coronary intervention, were enrolled. Patients were divided into a TCFA group (n=124) and a non-TCFA group (n=137). TCFA was defined as a lipid plaque (lipid content in ≥1 quadrant) covered with <70 µm-thickness fibrous caps. There were no differences in patient characteristics and clinical results between the 2 groups except for HDL-C level, low-density lipoprotein cholesterol (LDL-C) level, and high-sensitive C-reactive protein (hs-CRP) level. On multivariate regression analysis, low HDL-C level (ß coefficient: 0.302, P<0.001), high LDL-C level (ß coefficient: -0.172, P=0.008), hs-CRP level (ß coefficient: -0.145, P=0.017), and current smoking (ß coefficient: -0.124, P=0.028) were identified as independent contributors to fibrous cap thickness. CONCLUSIONS: HDL-C is correlated with fibrous cap thickness of the culprit lesion in patients with ACS. HDL-C may be considered as a therapeutic target for plaque stabilization.

Altered coronary flow velocity reserve and left ventricular wall motion dynamics: a phenomenon in hypertensive patients with ECG strain.

BACKGROUND: The inner-half layer of the left ventricular (LV) wall is primarily affected by ischemia and increased LV afterload. We hypothesized that LV wall thickening of inner-half layer and coronary microvascular function are impaired in hypertensive patients, especially in those with electrocardiographic (ECG) strain, which is a marker of LV hypertrophy and adverse prognosis. Therefore, the aim of this study is to investigate the association of the ratio of inner- to outer-half layer of the LV myocardial deformation and coronary microvascular function with ECG strain in hypertensive patients. METHODS: We studied 98 hypertensive patients and 13 controls. Hypertensive patients were divided into 2 groups, with (S+) and without (S-) ECG strain. Coronary flow velocity reserve (CFVR) of the left anterior descending artery was evaluated using transthoracic echocardiography. Circumferential and radial strains of the LV wall were analyzed by two-dimensional echocardiographic speckle tracking method, and the inner- to outer-half layer ratio (in/out ratio) was assessed. RESULTS: Coronary flow velocity reserve of S+ (2.06 ± 0.65) was significantly smaller than those in S- and controls (3.03 ± 0.65 and 3.38 ± 0.51, respectively). In/out ratio in both circumferential and radial strains were decreased as well as in S+ patients. Furthermore, in/out ratio was directly proportional to CFVR. CONCLUSIONS: Hypertensive patients with ECG strain possessed severely impaired CFVR and inner-half myocardial deformation. Moreover, the more severe the LV hypertrophy progresses, the greater is the impairment of coronary microvascular and LV inner-half myocardial deformation. Thus, CFVR and in/out ratio are useful quantitative markers that can render sensitive assessment of physiological changes in hypertensive heart disease.

Is visceral fat really a coronary risk factor? A multi-detector computed tomography study.

Metabolic syndrome (MS) is currently considered to be a risk factor for arteriosclerotic disease. The accumulation of visceral fat leads to arteriosclerotic disease after other risk factors have developed and either direct or mutual effects occur. The aim of this study was to verify whether visceral fat serves as an independent coronary risk factor. A total of 3157 patients who had undergone multi-detector computed tomography (MDCT) were analyzed via computed tomographic angiography and the measurement of their visceral fat area. Coronary arteries with > 70% stenosis were considered to be significant. The visceral fat area was measured at the umbilical level, and an area of 100 cm2 or more was defined as visceral obesity. Coronary risk factors (ie, hypertension, dyslipidemia, diabetes mellitus, family history, and smoking) were obtained from the patient medical records. The patients were divided into two groups: a visceral obesity group, 1130 patients (137.0 ± 31.1 cm2) and a nonvisceral obesity group, 2027 patients (57.3 ± 25.8 cm2). A significant difference in the incidence of coronary stenosis between the two groups was observed. According to multivariable analysis, the factors affecting coronary stenosis were age, gender, dyslipidemia, diabetes mellitus, and the ratio of visceral to subcutaneous fat. Visceral obesity was not found to be an independent coronary risk factor. Visceral obesity demonstrated the predominant presence of coronary risk factors.

Clinical significance of low signal intensity area surrounding stent struts identified by optical coherence tomography.

Previous intravascular ultrasound studies have shown that echolucent neointimal hyperplasia occasionally appears after bare-metal stent (BMS) or sirolimus-eluting stent (SES) implantation. Optical coherence tomography (OCT) studies have also demonstrated that paclitaxel-eluting stent (PES) restenosis exhibited similar images showing low signal intensity areas (LSIA) surrounding stent struts and three-layer appearance (TLA). The aim of the present study was to investigate the clinical significance of LSIA on OCT images in various types of stents. Fifty nine consecutive patients who underwent scheduled follow-up coronary angiography and OCT were enrolled. There was no significant difference in the prevalence of LSIA among the 3 stent groups (BMS 30%, SES 19%, PES 28%, P = 0.70). LSIA thickness was larger in the PES group than in the other stent groups (BMS 0.51 ± 0.21 mm, SES 0.35 ± 0.06 mm, PES 0.87 ± 0.19 mm, P < 0.01). The ratio of LSIA thickness to the neointimal thickness was also larger in PES compared with other stents (BMS 53 ± 9 %, SES 57 ± 8 %, PES 77 ± 5 %, P < 0.01). Also, LSIA thickness in patients with in-stent restenosis (ISR) was significantly larger than in those without ISR (0.37 ± 0.37 mm versus 0.12 ± 0.26 mm, P = 0.048). Our results suggest that LSIA might be involved in excessive neointimal formation, and that the healing response after PES implantation might be different from BMS or SES.

Inter-scan reproducibility of geometric coronary artery measurements using frequency-domain optical coherence tomography.

Frequency-domain optical coherence tomography (FD-OCT) is a novel technology which provides high-resolution cross-sectional images of coronary arteries. The aim of this study was to evaluate the inter-scan reproducibility of geometric FD-OCT measurements in the clinical setting. We examined 20 coronary lesions using FD-OCT. Following the FD-OCT image acquisition (1st pullback), and after the disengagement and re-engagement of the guiding catheter, an additional acquisition (2nd pullback) was performed using a new FD-OCT catheter. There was excellent correlation for minimum lumen area (r = 0.99, P < 0.001), lesion length (r = 0.99, P < 0.001) and lumen volume (r = 0.99, P < 0.001) between the 1st pullback and the 2nd pullback. The Bland-Altman test demonstrated good agreement between the 1st pullback and the 2nd pullback: the mean difference for minimum lumen area, lesion length, and lumen volume was 0.05 mm(2), 0.03 mm, and 0.70 mm(3), respectively; and the lower and upper limit of agreement for minimum lumen area, lesion length, and lumen volume was -0.58 and 0.48, -0.36 and 0.42, and -13.4 and 12.1, respectively. FD-OCT showed an excellent inter-scan reproducibility for the geometric coronary artery measurements. Our findings emphasize the value of FD-OCT as a tool for clinical longitudinal studies of coronary artery disease.

Prognostic value of Toll-like receptor 4 on human monocyte subsets combined with computed tomography-adapted Leaman score assessing coronary artery disease.

BACKGROUND: Upregulation of Toll-like receptor 4 (TLR-4) is associated with coronary plaque vulnerability assessed by coronary computed tomography angiography (CCTA). Computed tomography-adapted Leaman score (CT-LeSc) is an independent long-term predictor of cardiac events. The relationship between the TLR-4 expression of CD14 ++ CD16 + monocytes and future cardiac events is unknown. We investigated this relationship using CT-LeSc in patients with coronary artery disease (CAD). METHODS: We analyzed 61 patients with CAD who underwent CCTA. Three monocyte subsets (CD14 ++ CD16 - , CD14 ++ CD16 + , and CD14 + CD16 + ) and the expression of TLR-4 were measured by flow cytometry. We divided the patients into two groups according to the best cutoff value of the TLR-4 expression on CD14 + CD16 + which could predict future cardiac events. RESULTS: CT-LeSc was significantly greater in the high TLR-4 group than the low TLR-4 group [9.61 (6.70-13.67) vs. 6.34 (4.27-9.09), P  < 0.01]. The expression of TLR-4 on CD14 ++ CD16 + monocytes was significantly correlated with CT-LeSc ( R2  = 0.13, P  < 0.01). The expression of TLR-4 on CD14 ++ CD16 + monocytes was significantly higher in patients who had future cardiac events than in those who did not [6.8 (4.5-9.1) % vs. 4.2 (2.4-7.6) %, P  = 0.04]. High TLR-4 expression on CD14 ++ CD16 + monocytes was an independent predictor for future cardiac events ( P  = 0.01). CONCLUSION: An increase in the TLR-4 expression on CD14 ++ CD16 + monocytes is related to the development of future cardiac events.

Effect of strut thickness on neointimal atherosclerotic change over an extended follow-up period (≥ 4 years) after bare-metal stent implantation: intracoronary optical coherence tomography examination.

BACKGROUND: Neointima inside the bare-metal stents (BMSs) can transform into atherosclerotic tissue during an extended follow-up because of a persistent inflammatory reaction to the metal. We sought to investigate whether strut thickness may impact on the atherosclerotic change in neointima 4 years or more after BMS implantation using optical coherence tomography. METHODS: Forty-six stented lesions of 41 patients with BMS ≥ 4 years after implantation who underwent optical coherence tomography were enrolled in the study. The strut was defined as thin when less than 100 µm and thick when ≥ 100 µm. According to these criteria, stents were divided into 2 groups (thin strut n = 19, thick strut n = 27). Neointimal tissue was categorized into normal neointima, characterized by a signal-rich band without signal attenuation, or lipid-laden intima, with marked signal attenuation and a diffuse border. Intimal disruption, thrombus, and neovascularization were also evaluated. RESULTS: The mean period after implantation was 98.2 ± 25.8 months in the thin-strut group and 91.1 ± 22.8 months in the thick-strut group (P = .330). Lipid-laden intima (70% vs 32%, P = .016), thin-cap fibroatheroma-like intima (59% vs 16%, P = .0056), and intimal disruption (48% vs 16%, P = .031) were observed more frequently in the thick-strut group than in the thin-strut group, but no significant difference was observed in the frequency of thrombus. Although peristrut neovascularization was a common finding in both groups (thick vs thin 81% vs 79%, P = 1.000), the frequency of intraintima neovascularization tended to be higher in the thick-strut group (67% vs 42%, P = .135). CONCLUSIONS: A thinner strut thickness may have favorable effects on neointimal atherosclerotic changes after BMS implantation.

Impact of stress hyperglycemia on myocardial salvage following successfully recanalized primary acute myocardial infarction.

BACKGROUND: Elevated blood glucose on admission may worsen outcome after acute myocardial infarction (AMI). No relationship has been identified between admission blood glucose level and myocardial salvage in patients with AMI. METHODS AND RESULTS: This study assessed 150 consecutive patients with a first AMI who underwent percutaneous coronary intervention within 24 h from onset of symptoms. Plasma blood glucose was measured on admission. Stress hyperglycemia was defined as blood glucose ≥10 mmol/L (180 mg/dl). The extent of myocardial salvage 7 days after AMI was evaluated on cardiovascular magnetic resonance imaging (CMRI) as the difference between areas of myocardium at risk (T2-weighted hyperintense lesion) and areas of late gadolinium enhancement. The association between stress hyperglycemia and myocardial salvage index (MSI) was investigated in patients with and without diabetes. Among non-diabetic patients, MSI was lower in those with stress hyperglycemia than in those without. No significant difference in MSI was noted between diabetes patients with or without stress hyperglycemia. On multivariate analysis, stress hyperglycemia in patients without diabetes was an independent predictor of MSI. CONCLUSIONS: Stress hyperglycemia affects MSI, indicating that the manipulation of glucose levels could be a potential therapeutic target for salvaging ischemic damage.

Circulating CD14+CD16+ monocyte subsets as biomarkers of the severity of coronary artery disease in patients with stable angina pectoris.

BACKGROUND: Circulating monocytes can be divided into 2 subsets typically identified by the expression of CD14 and CD16. Although previous studies have shown that circulating monocytes contribute to the progression of coronary atherosclerotic lesions, the relationship between the severity of coronary artery disease (CAD) and the 2 distinct monocyte subsets has not previously been evaluated. We investigated the relationship between the monocyte subsets and the severity of CAD assessed by coronary angiography (CAG) in patients with stable angina pectoris (SAP). METHODS AND RESULTS: We enrolled 125 patients who underwent diagnostic CAG. Patients were divided into 3 groups: those without CAD, those with single-vessel disease (SVD), and those with multiple-vessel disease (MVD). In addition, the severity of CAD was evaluated by Gensini score. The 2 monocyte subsets (CD14(+)CD16(-) and CD14(+)CD16(+)) were measured by flow cytometry. Circulating CD14(+)CD16(+) monocytes were more frequently observed in patients with MVD than in those with SVD or without CAD. The proportion of CD14(+)CD16(+) monocytes positively correlated with Gensini score (r=0.618, P<0.001). Multivariate logistic regression analysis revealed that the proportion of CD14(+)CD16(+) monocytes was an independent contributor to MVD (odds ratio: 1.475; 95% confidence interval: 1.273-1.708, P<0.001). CONCLUSIONS: A preferential increase in peripheral CD14(+)CD16(+) monocytes may be closely related to the severity of CAD in patients with SAP.