Hiroto Tsujioka

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.

Morphology of Exertion-Triggered Plaque Rupture in Patients With Acute Coronary Syndrome An Optical Coherence Tomography Study

Background— Plaque rupture and secondary thrombus formation play key roles in the onset of acute coronary syndrome (ACS). One pathological study suggested that the morphologies of plaque rupture differed between rest-onset and exertion-triggered rupture in men who experienced sudden death. The aim of the present study was to use optical coherence tomography to investigate the relationship in patients with ACS between the morphology of a ruptured plaque and the patients activity at the onset of ACS. Methods and Results— The study population was drawn from 43 consecutive ACS patients (with or without ST-segment elevation) who underwent optical coherence tomography and presented with a ruptured plaque at the culprit site. Patients were divided into a rest group and an exertion group on the basis of their activities at the onset of ACS. The thickness of the broken fibrous cap correlated positively with activity at the onset of ACS. The culprit plaque ruptured at the shoulder more frequently in the exertion group than in the rest group (rest 57% versus exertion 93%, P=0.014). The thickness of the broken fibrous cap in the exertion group was significantly higher than in the rest-onset group (rest onset: 50 &mgr;m [interquartile median 15 &mgr;m]; exertion: 90 &mgr;m [interquartile median 65 &mgr;m], P<0.01). Conclusions— The morphologies of exertion-triggered and rest-onset ruptured plaques differ in ACS patients. Our data suggest that a thin-cap fibroatheroma is a lesion predisposed to rupture both at rest and during the patients day-to day activity, and some plaque rupture may occur in thick fibrous caps depending on exertion levels.

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.

Renin Inhibitor Aliskiren Improves Impaired Nitric Oxide Bioavailability and Protects Against Atherosclerotic Changes

We investigated whether aliskiren, a direct renin inhibitor, improves NO bioavailability and protects against spontaneous atherosclerotic changes. We also examined the effects of cotreatment with aliskiren and valsartan, an angiotensin II receptor blocker, on the above-mentioned outcomes. Watanabe heritable hyperlipidemic rabbits were treated with vehicle (control), aliskiren, valsartan, or aliskiren plus valsartan for 8 weeks. Then, acetylcholine-induced NO production was measured as a surrogate index of endothelium protective function, and both superoxide and vascular peroxynitrite were measured. Tetrahydrobiopterin in aortic segments was assessed by high-performance liquid chromatography with fluorescence detection. Plaque area was quantified by histology. Increase in plasma NO concentration in response to intra-aortic acetylcholine infusion was significantly greater in all of the test groups than in controls. Aliskiren+valsartan cotreatment increased acetylcholine-induced NO by 6.2 nmol/L, which was significantly higher than that with either aliskiren or valsartan alone. Vascular superoxide and peroxynitrite levels were both significantly higher in controls and significantly lower in the aliskiren+valsartan group than in the aliskiren or valsartan group. The highest tetrahydrobiopterin levels were observed after aliskiren+valsartan cotreatment. Histology of the thoracic aorta revealed that the plaque area was significantly decreased with combination therapy compared with monotherapy. Treatment with a direct renin inhibitor has protective effects on endothelial function and atherosclerotic changes. Furthermore, cotreatment with a direct renin inhibitor and an angiotensin II receptor blocker has additive protective effects on both.

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.

Distribution and frequency of thin-capped fibroatheromas and ruptured plaques in the entire culprit coronary artery in patients with acute coronary syndrome as determined by optical coherence tomography.

The aim of this study was to investigate the distribution and frequency of thin-capped fibroatheromas (TCFAs) within the entire length of culprit coronary arteries in patients with acute coronary syndrome. Our population was drawn from 43 consecutive patients with acute coronary syndrome (with or without ST-segment elevation) who underwent optical coherence tomography to visualize the entire culprit coronary artery using a nonocclusive optical coherence tomographic technique. Patients were categorized divided into a TCFA group or a no-TCFA group on the basis of the optical coherence tomographic findings. There were no differences in baseline characteristics or angiographic findings between the 2 groups. High-sensitive C-reactive protein in the TCFA group was significantly higher than in the no-TCFA group (median 3.3 mg/L, interquartile 3.1, vs 1.7 mg/L, interquartile 2.2, p = 0.03). Plaque rupture was found in 28 patients (65%) and multiple plaque ruptures in 5 patients (12%). Optical coherence tomogram revealed 21 TCFAs in 18 patients (42%). Multiple TCFAs were found in the same vessel in 3 patients (7%). The distribution of TCFAs in the right coronary arteries of our subject population was relatively even (proximal 2 [12%], mid 5 [29%], distal 3 [18%], p = 0.42), whereas TCFAs in the left anterior descending artery were common in proximal sites (proximal 6 [27%], mid 2 [9%], distal 0, p = 0.018). In conclusion, the use of optical coherence tomography to look for TCFAs and identify their distribution when combined with C-reactive protein may contribute to forming a strategy for preventing impending coronary events.

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.