Kohei Ishibashi

Impact of Heterogeneity of Human Peripheral Blood Monocyte Subsets on Myocardial Salvage in Patients With Primary Acute Myocardial Infarction

OBJECTIVES We examined whether distinct monocyte subsets contribute in specific ways to myocardial salvage in patients with acute myocardial infarction (AMI). BACKGROUND Recent studies have shown that monocytes in human peripheral blood are heterogeneous. METHODS We studied 36 patients with primary AMI. Peripheral blood sampling was performed 1, 2, 3, 4, 5, 8, and 12 days after AMI onset. Two monocyte subsets (CD14(+)CD16(-) and CD14(+)CD16(+)) were measured by flow cytometry. The extent of myocardial salvage 7 days after AMI was evaluated by cardiovascular magnetic resonance imaging as the difference between myocardium at risk (T2-weighted hyperintense lesion) and myocardial necrosis (delayed gadolinium enhancement). Cardiovascular magnetic resonance imaging was also performed 6 months after AMI. RESULTS Circulating CD14(+)CD16(-) and CD14(+)CD16(+) monocytes increased in AMI patients, peaking on days 3 and 5 after onset, respectively. Importantly, the peak levels of CD14(+)CD16(-) monocytes, but not those of CD14(+)CD16(+) monocytes, were significantly negatively associated with the extent of myocardial salvage. We also found that the peak levels of CD14(+)CD16(-) monocytes, but not those of CD14(+)CD16(+) monocytes, were negatively correlated with recovery of left ventricular ejection fraction 6 months after infarction. CONCLUSIONS The peak levels of CD14(+)CD16(-) monocytes affect both the extent of myocardial salvage and the recovery of left ventricular function after AMI, indicating that the manipulation of monocyte heterogeneity could be a novel therapeutic target for salvaging ischemic damage.

Advantage of next-generation frequency-domain optical coherence tomography compared with conventional time-domain system in the assessment of coronary lesion.

Background: Intracoronary optical coherence tomography (OCT) is a high‐resolution imaging modality used for evaluation of coronary lesion morphology. However, current time‐domain OCT (TD‐OCT) have a number of limitations with regard to both procedural usage and safety in the clinical setting. The next‐generation frequency‐domain OCT (FD‐OCT), which has a much faster frame rate and pullback speed than TD‐OCT, is expected to overcome these limitations. The aim of this study was to evaluate the feasibility and usability of next generation FD‐OCT in the assessment of coronary lesions. Methods: A comparison study was performed between FD‐OCT and TD‐OCT from the aspect of usability (set‐up time), qualitatively (rate of clear image segment), and safety (adverse event) in 14 ischemic heart disease patients with 20 previously implanted coronary stents. Results: The mean time of the OCT procedure in this study from setup to completion of image acquisition was 3.2 ± 0.8 min for FD‐OCT and 11.2 ± 2.5 min for TD‐OCT (P < 0.01). In qualitative image assessment, FD‐OCT has the potential to yield a higher rate of clear image segments (CIS) than TD‐OCT (99.4% vs. 80.8%, respectively; P < 0.01). In addition to these improved characteristics, there were no ischemic ECG changes or arrhythmia associated with FD‐OCT. Conclusions: The next‐generation intracoronary FD‐OCT has better performance in the clinical setting and the potential to overcome several limitations of conventional TD‐OCT systems.

Difference of Culprit Lesion Morphologies Between ST-Segment Elevation Myocardial Infarction and Non–ST-Segment Elevation Acute Coronary Syndrome : An Optical Coherence Tomography Study

OBJECTIVES The aim of this study was to investigate the difference of culprit lesion morphologies assessed by optical coherence tomography (OCT) between ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndrome (NSTEACS). BACKGROUND Autopsy studies have reported that rupture of a thin-cap fibroatheroma and subsequent thrombus formation is the most important mechanism leading to acute coronary syndrome (ACS). Optical coherence tomography is a high-resolution imaging modality that is capable of investigating detailed coronary plaque morphology in vivo. METHODS We examined the culprit lesion morphologies by OCT in 89 consecutive patients with acute coronary syndrome (STEMI = 40; NSTEACS = 49). RESULTS The incidence of plaque rupture, thin-cap fibroatheroma, and red thrombus was significantly higher in STEMI compared with NSTEACS (70% vs. 47%, p = 0.033, 78% vs. 49%, p = 0.008, and 78% vs. 27%, p < 0.001, respectively). Although the lumen area at the site of plaque rupture was similar in the both groups (2.44 ± 1.34 mm(2) vs. 2.96 ± 1.91 mm(2), p = 0.250), the area of ruptured cavity was significantly larger in STEMI compared with NSTEACS (2.52 ± 1.36 mm(2) vs. 1.67 ± 1.37 mm(2), p = 0.034). Furthermore, the ruptured plaque of which aperture was open-wide against the direction of coronary flow was more often seen in STEMI compared with NSTEACS (46% vs. 17%, p = 0.036). CONCLUSIONS The present OCT study demonstrated the differences of the culprit lesion morphologies between STEMI and NSTEACS. The morphological feature of plaque rupture and the intracoronary thrombus could relate to the clinical presentation in patients with acute coronary disease.

Lipid-rich plaque and myocardial perfusion after successful stenting in patients with non-ST-segment elevation acute coronary syndrome: an optical coherence tomography study

AIMS Although some recent guidelines recommend an early invasive strategy for non-ST-segment elevation acute coronary syndrome (NSTEACS), several studies have failed to identify any benefit for very early intervention for NSTEACS. The no-reflow phenomenon may inhibit the expected benefit from very early recanalization for NSTEACS subjects. The aim of this study was to investigate whether optical coherence tomography (OCT) could predict no-reflow in patients with NSTEACS. METHODS AND RESULTS This study comprised 83 consecutive patients with NSTEACS who underwent OCT and successful emergent primary stenting. On the basis of post-stent TIMI flow, patients were divided into two groups: no-reflow group (n = 14) and reflow group (n = 69). Thin-cap fibroatheroma (TCFA) was defined as a plaque presenting lipid content for >90 degrees , and with thinnest part of the fibrous cap measuring <70 microm. Thin-cap fibroatheroma were more frequently observed in the no-reflow group than in the reflow group (50% vs. 16%, P = 0.005). The frequency of the no-reflow phenomenon increases according to the size of the lipid arc in the culprit plaque. Final TIMI blush grade also deteriorated according to the increase in the lipid arc. A multivariable logistic regression model revealed that lipid arc alone was an independent predictor of no-reflow (odds ratio 1.018; CI 1.004-1.033; P = 0.01). CONCLUSION Optical coherence tomography can predict no-reflow after percutaneous coronary intervention (PCI) in NSTEACS. The lipid contents of a culprit plaque may play a key role in damage to the microcirculation after PCI for NSTEACS. From our results, it is found that OCT is useful tool for stratifying risk for PCI for NSTEACS.

Multiple Coronary Lesion Instability in Patients With Acute Myocardial Infarction as Determined by Optical Coherence Tomography

Autopsy studies have suggested that acute myocardial infarction (AMI) represents a pan-coronary process of vulnerable plaque development. We performed multifocal optical coherence tomographic (OCT) examination to compare coronary lesion instability between AMI and stable angina pectoris (SAP). A total of 42 patients with AMI (n = 26) or SAP (n = 16) who had multivessel disease and underwent multivessel coronary intervention were enrolled in the present study. The OCT examination was performed not only in the infarct-related/target lesions, but also in the noninfarct-related/nontarget lesions. OCT-derived thin-cap fibroatheroma (TCFA) was defined as a lesion with a fibrous cap thickness of <65 microm. In the infarct-related/target lesions, plaque rupture (77% vs 7%, p <0.001) and intracoronary thrombus (100% vs 0%, p <0.001) were observed more frequently in AMI than in SAP. The fibrous cap thickness (57 + or - 12 vs 180 + or - 65 microm, p <0.001) was significantly thinner in AMI and the frequency of OCT-derived TCFA (85% vs 13%, p <0.001) was significantly greater in AMI than in SAP. In the noninfarct-related/nontarget lesions, the frequency of plaque rupture was not different between the 2 groups. Intracoronary thrombus was observed in 8% of AMI, but it was not found in SAP. The fibrous cap thickness (111 + or - 65 vs 181 + or - 70 microm, p = 0.002) was significantly thinner in AMI and the frequency of OCT-derived TCFA (38% vs 6%, p = 0.030) was significantly greater in AMI than in SAP. Multiple OCT-derived TCFAs in both the infarct-related/target and the noninfarct-related/nontarget lesions were observed in 38% of patients with AMI but not in patients with SAP (p = 0.007). In conclusion, the present OCT examination demonstrated multiple lesion instability in the presence of AMI.

Association of monocyte subsets with vulnerability characteristics of coronary plaques as assessed by 64-slice multidetector computed tomography in patients with stable angina pectoris.

OBJECTIVE The aim of the present study was to examine the relation between monocyte subsets and the presence, extent, and vulnerability characteristics of non-calcified coronary plaques (NCPs) as assessed by multidetector computed tomography (MDCT). METHODS We studied 73 patients with stable angina pectoris who underwent MDCT. Two monocyte subsets (CD14(+)CD16(-) and CD14(+)CD16(+)) were measured by flow cytometry. Coronary artery plaques were assessed by 64-slice MDCT. We defined NCP vulnerability according to the presence of positive remodeling (remodeling index>1.05) and/or low CT attenuation plaques (<35 HU). RESULTS A total of 40 (55%) patients had identifiable vulnerable plaques. The relative proportion of CD14(+)CD16(+) monocytes was significantly greater in patients with 1 or multiple vulnerable plaques than in patients with no vulnerable plaques or control (healthy) subjects. In addition, the relative proportion of CD14(+)CD16(+) monocytes was positively correlated with remodeling index (r=0.40, P<0.01) and negatively correlated with CT attenuation value (r=-0.34, P<0.01). CONCLUSION The present results suggest that an increased subset of CD14(+)CD16(+) monocytes is related to coronary plaque vulnerability in patients with stable angina pectoris.

Association of monocyte subset counts with coronary fibrous cap thickness in patients with unstable angina pectoris

OBJECTIVES We examined whether distinct monocyte subsets relate in specific ways to coronary fibrous cap thickness (FCT) in patients with unstable angina pectoris (UAP). METHODS Forty patients with UAP who underwent percutaneous coronary intervention were enrolled in this study. The changes in the non-culprit FCT were assessed by optical coherence tomography (OCT) at baseline and after 9 months. The distinct monocyte subsets (CD14+CD16-CCR2+ and CD14+CD16+CX3CR1+) were measured by flow cytometry. RESULTS The percent change in FCT showed significantly negative correlation with the percent changes in CD14+CD16+CX3CR1+ monocytes, but not CD14+CD16-CCR2+ monocytes. In addition, the percent change in CD14+CD16+CX3CR1+ monocytes was significantly decreased in the group of patients who received statin treatment compared with the group of patients who did not. Of interest, there was a close relationship between CD14+CD16+CX3CR1+ monocytes and levels of C-reactive protein, but not lipid profiles, including low-density lipoprotein cholesterol and low-/high-density lipoprotein cholesterol ratio. CONCLUSIONS CD14+CD16+CX3CR1+ monocytes may have a role in coronary plaque vulnerability.

The effect of lipid and inflammatory profiles on the morphological changes of lipid-rich plaques in patients with non-ST-segment elevated acute coronary syndrome: follow-up study by optical coherence tomography and intravascular ultrasound.

OBJECTIVES The aim of this study was to determine the relationship between the morphological changes of nonculprit lipid-rich plaques and several clinical profiles in patients with non-ST-segment elevated acute coronary syndrome (NSTEACS). BACKGROUND Identification of coronary lesion with morphological characteristics of rupture-prone plaques is still difficult. METHODS Eighty-two consecutive patients with NSTEACS who underwent percutaneous coronary intervention were enrolled. The changes in total atheroma volume (TAV) of residual nonculprit lipid-rich plaques and the changes in the corresponding fibrous cap thickness (FCT) were assessed by intravascular ultrasound and optical coherence tomography, respectively, at baseline and after 9 months. RESULTS The percentage changes in TAV (mm(3)) of lipid-rich plaques and in the corresponding FCT (microm) over the 9-month follow-up period were 3.1 +/- 11% and 15 +/- 17%, respectively. There was no significant correlation between the changes in TAV and those in FCT. The change in TAV showed a significant correlation with reduction of the low-density lipoprotein/high-density lipoprotein (LDL/HDL) ratio (r = 0.42, p < 0.01). In contrast, the change in FCT showed no correlation with LDL/HDL ratio but had a significant positive correlation with changes in high-sensitivity C-reactive protein (r = 0.44, p < 0.01). Furthermore, in multivariate logistic analysis, statin use was an independent predictor of changes in well-stabilized plaques that showed both TAV reduction and FCT increase. CONCLUSIONS The changes in TAV and FCT of coronary plaques over a 9-month observation period were related to 2 different independent factors (i.e., reduction of LDL-cholesterol and high-sensitivity C-reactive protein, respectively). Furthermore, lipid-lowering therapy with statin has the potential to stabilize these parameters by both plaque reduction and FCT.

Prevalence and Clinical Significance of Papillary Muscle Infarction Detected by Late Gadolinium-Enhanced Magnetic Resonance Imaging in Patients With ST-Segment Elevation Myocardial Infarction

Background— The frequency of papillary muscle infarction (PapMI) without rupture has not been fully investigated in vivo. Furthermore, the relationship between papillary muscle dysfunction and mitral regurgitation (MR) has been controversial in patients with ST-segment elevation myocardial infarction. Therefore, the aim of this study was to assess the frequency and clinical characteristics of PapMI without rupture using late gadolinium-enhanced magnetic resonance imaging (MRI) in patients with ST-segment elevation myocardial infarction. Methods and Results— One hundred eighteen ST-segment elevation myocardial infarction patients with primary percutaneous coronary intervention underwent cardiac MRI twice 9±4 days and 8±1 months (n=104) after myocardial infarction. MR was categorized by echocardiography. Of these patients, 40% were found to have late gadolinium enhancement of papillary muscle, in which the posterior papillary muscle was involved more frequently than the anterior papillary muscle (77% versus 26%; P<0.001). PapMI was encountered more frequently in patients with left circumflex and right coronary artery lesions compared with left anterior descending artery lesion (78%, 48%, and 13%; P<0.001). By multiple logistic regression analysis, only coaptation height was identified as an independent predictor of the presence of MR. The second cardiac magnetic resonance imaging showed that the infarct size had a positive correlation with left ventricular end-diastolic volume (r=0.41, P<0.001) and that PapMI was not associated with left ventricular remodeling (P=0.31). Deterioration of MR was not observed in patients with PapMI. Conclusions— PapMI is more frequent than previously thought yet appears to have significant clinical latency. The size of the myocardial infarction, but not the presence of PapMI, seems to affect left ventricular remodeling, and PapMI is not obligatorily associated with MR.

Differential expression of Toll-like receptor 4 and human monocyte subsets in acute myocardial infarction

OBJECTIVE To investigate the involvement of Toll-like receptor 4 (TLR4) expression on two monocyte subsets in the pathologic processes related to acute coronary syndrome. How monocytes, which have recently been shown to comprise two distinct subsets, mediate the process of coronary plaque rupture remains to be fully elucidated. Recent studies have shown that TLR4 is involved in monocyte activation of patients with accelerated forms of atherosclerosis. METHODS We enrolled 65 patients with acute myocardial infarction (AMI, n=22), unstable angina pectoris (UAP, n=16), and stable angina pectoris (SAP, n=27) who underwent coronary angiography and 15 healthy controls. The expression of TLR4 on two monocyte subsets (CD14(+)CD16(-) and CD14(+)CD16(+)) was measured by flow cytometry. RESULTS In patients with AMI, TLR4 was more expressed on circulating CD14(+)CD16(+) monocytes than on CD14(+)CD16(-) monocytes (p<0.001). The expression levels of TLR4 on CD14(+)CD16(+) monocytes were significantly elevated in patients with AMI compared with other 3 groups. TLR4 expression levels on CD14(+)CD16(+) monocytes were significantly elevated at the culprit site compared with the systemic level (p=0.044). The up-regulation of TLR4 on admission was remarkably decreased 12 days after AMI (p<0.001). In addition, plasma levels of tumor necrosis factor-α were positively correlated with TLR4 expression levels on monocytes in patients with AMI (r=0.47, p=0.027). CONCLUSION TLR overexpression on CD14(+)CD16(+) monocytes in AMI, as demonstrated both in the circulation and at the coronary culprit site, might be associated with the pathogenesis of AMI.