Kenei Shimada

Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation.

OBJECTIVES The purpose of this document is to make the output of the International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT) Standardization and Validation available to medical and scientific communities, through a peer-reviewed publication, in the interest of improving the diagnosis and treatment of patients with atherosclerosis, including coronary artery disease. BACKGROUND Intravascular optical coherence tomography (IVOCT) is a catheter-based modality that acquires images at a resolution of ~10 μm, enabling visualization of blood vessel wall microstructure in vivo at an unprecedented level of detail. IVOCT devices are now commercially available worldwide, there is an active user base, and the interest in using this technology is growing. Incorporation of IVOCT in research and daily clinical practice can be facilitated by the development of uniform terminology and consensus-based standards on use of the technology, interpretation of the images, and reporting of IVOCT results. METHODS The IWG-IVOCT, comprising more than 260 academic and industry members from Asia, Europe, and the United States, formed in 2008 and convened on the topic of IVOCT standardization through a series of 9 national and international meetings. RESULTS Knowledge and recommendations from this group on key areas within the IVOCT field were assembled to generate this consensus document, authored by the Writing Committee, composed of academicians who have participated in meetings and/or writing of the text. CONCLUSIONS This document may be broadly used as a standard reference regarding the current state of the IVOCT imaging modality, intended for researchers and clinicians who use IVOCT and analyze IVOCT data.

Spotty Calcification Typifies the Culprit Plaque in Patients With Acute Myocardial Infarction An Intravascular Ultrasound Study

Background—Calcification is a common finding in human coronary arteries; however, the relationship between calcification patterns, plaque morphology, and patterns of remodeling of culprit lesions in a comparison of patients with acute coronary syndromes (ACS) and those with stable conditions has not been documented. Methods and Results—Preinterventional intravascular ultrasound (IVUS) images of 178 patients were studied, 61 with acute myocardial infarction (AMI), 70 with unstable angina pectoris (UAP), and 47 with stable angina pectoris (SAP). The frequency of calcium deposits within an arc of less than 90° for all calcium deposits was significantly different in culprit lesions of patients with AMI, UAP, and SAP (P<0.0001). Moreover, the average number of calcium deposits within an arc of <90° per patient was significantly higher in AMI than in SAP (P<0.0005; mean±SD, AMI 1.4±1.3, SAP 0.5±0.8). Conversely, calcium deposits were significantly longer in SAP patients (P<0.0001; mean±SD, AMI 2.2±1.6, UAP 1.9±1.8, and SAP 4.3±3.2 mm). In AMI patients, the typical pattern was spotty calcification, associated with a fibrofatty plaque and positive remodeling. In ACS patients showing negative remodeling, no calcification was the most frequent observation. Conversely, SAP patients had the highest frequency of extensive calcification. Conclusions—Our observations show that IVUS allows the identification of vulnerable plaques in coronary arteries, not only by identifying a fibrofatty plaque and positive remodeling, but also by identifying a spotty pattern of calcification.

Implications of plasma concentrations of adiponectin in patients with coronary artery disease

Objective: To investigate whether concentrations of plasma adiponectin constitute a significant coronary risk factor, with particular focus on the relation between plasma concentrations of adiponectin and the development of acute coronary syndrome (ACS). Subjects and methods: Plasma concentrations of adiponectin were measured in 123 patients with coronary artery disease (CAD) and in 17 control participants. Patients were divided into three groups according to condition type: acute myocardial infarction (AMI) group (n  =  59), unstable angina pectoris (UAP) group (n  =  28), and stable angina pectoris (SAP) group (n  =  36). Results: Plasma concentrations of adiponectin correlated negatively with body mass index (r  =  −0.18, p < 0.05), serum triglyceride (r  =  −0.25, p < 0.01), and fasting glucose concentrations (r  =  −0.21, p < 0.05), but correlated positively with age (r  =  0.26, p < 0.01), high density lipoprotein cholesterol concentrations (r  =  0.35, p < 0.01), and low density lipoprotein particle size (r  =  0.37, p < 0.01). Plasma concentrations of adiponectin in patients with ACS, in both the AMI and UAP groups, were significantly lower than those in patients with SAP and in the control group (ACS, 6.5 (3.0) μg/ml; SAP, 11.3 (5.9) μg/ml; control 12.8 (4.3) μg/ml; p < 0.01). Additionally, plasma concentrations of adiponectin in patients with CAD (7.9 (4.6) μg/ml, p < 0.01) were significantly lower than in the control group. There were, however, no significant differences between patients with SAP and the control group (p  =  0.36). Multiple logistic regression analysis showed that smoking, fasting glucose concentration, and low log adiponectin concentration correlated independently with the development of an ACS. Conclusions: The findings suggest that measurement of plasma concentrations of adiponectin may be of use for assessing the risk of CAD and may be related to the development of ACS.

No-reflow phenomenon and lesion morphology in patients with acute myocardial infarction.

Background—The no-reflow phenomenon is associated with poor functional and clinical outcomes for patients with acute myocardial infarction (AMI). In the era of primary intervention, accurately identifying lesions at high risk of no reflow is of crucial importance. At present, no study into the relationship between lesion morphology and no reflow has been performed. The aim of this study was to investigate the relationship between preintervention intravascular ultrasound (IVUS) lesion morphology and the no-reflow phenomenon. Methods and Results—This study comprised 100 consecutive patients with AMI who underwent preintervention IVUS and were successfully recanalized with primary balloon angioplasty or stenting. IVUS was again performed to identify and exclude any mechanical vessel obstruction in cases of thrombolysis in myocardial infarction flow grade 0, 1, or 2 after intervention in the absence of angiographic stenosis. Angiographic no reflow was seen in 13 patients (13%). Univariate analysis indicated that hypercholesterolemia, fissure and dissection, lipid pool–like image, lesion, and reference external elastic membrane cross-sectional area correlate with the no-reflow phenomenon. Multivariate logistic regression analysis showed that lipid pool–like image (P <0.05; odds ratio 118; 95% CI, 1.28 to 11 008) and lesion elastic membrane cross-sectional area (P <0.05; odds ratio 1.55; 95% CI 1.01 to 2.38) are independent predictive factors of no-reflow phenomenon after reperfusion for AMI. Conclusions—Large vessels with lipid pool–like image are at high risk for no reflow after primary intervention for AMI. Also, plaque content may play a role in damage to the microcirculation after primary intervention for AMI.

Napkin-Ring Sign on Coronary CT Angiography for the Prediction of Acute Coronary Syndrome

OBJECTIVES The aim of this study was to determine the predictive value of the napkin-ring sign on coronary computed tomography angiography (CTA) for future acute coronary syndrome (ACS) events in patients with coronary artery disease. BACKGROUND Recent studies have reported a close association between the napkin-ring sign on coronary CTA and thin-cap fibroatheroma. METHODS The subjects of this prospective study were 895 consecutive patients who underwent coronary CTA examination and were followed for >1 year. The primary endpoint was an ACS event (cardiac death, nonfatal myocardial infarction, or unstable angina pectoris). The coronary CTA analysis included the presence of obstructive plaque, positive remodeling (PR), low-attenuation plaque (LAP), and the napkin-ring sign. The napkin-ring sign was defined by the following criteria: 1) the presence of a ring of high attenuation around certain coronary artery plaques; and 2) attenuation of the ring presenting higher than those of the adjacent plaque and no >130 Hounsfield units. RESULTS Of the 12,727 segments, 1,174 plaques were observed, including plaques with PR in 130 segments (1.0%), LAP in 107 segments (0.8%), and napkin-ring signs in 45 segments (0.4%). Thirty-six of the 45 plaques with napkin-ring signs (80%) overlapped with those showing either PR or LAP. During the follow-up period (2.3 ± 0.8 years), 24 patients (2.6%) experienced ACS events, and plaques developed in 41% with a napkin-ring sign. Segment-based Cox proportional hazards models analysis showed that PR (p < 0.001), LAP (p = 0.007), and the napkin-ring sign (p < 0.0001) were independent predictive factors for future ACS events. Kaplan-Meier analysis demonstrated that plaques with napkin-ring signs showed a higher risk of ACS events compared with those without a napkin-ring sign. CONCLUSIONS The present study demonstrated for the first time that the napkin-ring sign demonstrated on coronary CTA was strongly associated with future ACS events, independent of other high-risk coronary CTA features. Detection of the napkin-ring sign could help identify coronary artery disease patients at high risk of future ACS events.

C-Reactive Protein and Lesion Morphology in Patients With Acute Myocardial Infarction

Background Elevated serum C‐reactive protein (CRP) is of clinical significance in the management of acute coronary syndromes, but there have been few in vivo studies detailing the relation between lesion morphology and elevated CRP in the setting of acute myocardial infarction (AMI). In this study, we investigated the relation between lesion morphology as seen under preintervention intravascular ultrasound (IVUS) and CRP in the acute phase of AMI. Methods and Results Our patient population comprised 90 consecutive patients with AMI who underwent preintervention IVUS within 6 hours of the onset of symptoms. Patients were divided into an elevated CRP group (≥3 mg/L) or a normal CRP group on the basis of serum CRP levels. There were no differences in patient characteristics or angiographic findings. We observed significantly more plaque rupture in the elevated CRP group than in the normal CRP group (70% versus 43%, P=0.01). A multivariate logistic regression model revealed that the presence of ruptured plaque alone correlated with elevation of serum CRP (P=0.02; odds ratio, 3.35; 95% CI, 1.22 to 9.18). Conclusions Elevated CRP may be related to the presence of ruptured plaque. Our results suggest that in the setting of AMI, elevated CRP levels may reflect the inflammatory activity of a ruptured plaque. (Circulation. 2003;108:282‐285.)

Flow-mediated vasodilation as a diagnostic modality for vascular failure.

Vascular endothelial dysfunction represents an initial step of “vascular failure,” which we have recently proposed as a comprehensive syndrome of failed vascular functions that extends from risk factors to established atherosclerotic disease. The early detection of vascular failure is essential in order to appropriately intervene and prevent its progression. Many efforts have been made to assess vascular endothelial function, and one of the most promising methods is the measurement of endothelium-dependent flow-mediated vasodilation (FMD) using high-frequency ultrasonographic imaging and transient occlusion of the brachial artery. The reactive hyperemia caused by the transient brachial arterial occlusion induces the release of local nitric oxide, resulting in vasodilation that can be quantified as an index of vasomotor function. The noninvasive nature of this technique allows repeated measurements over time to study the effectiveness of various interventions that may affect vascular health. Although there are technical and interpretive limitations of this technique, FMD-guided therapeutic approaches for vascular failure should contribute to the improvement of cardiovascular mortality and morbidity.

Effect of red wine on coronary flow-velocity reserve

An increase in coronary flow-velocity reserve may be one of the important cardioprotective effects of red wine. Some polyphenols may have potent vasorelaxing effects on coronary microvessels during hyperaemia.

Repeated remote ischemic conditioning attenuates left ventricular remodeling via exosome-mediated intercellular communication on chronic heart failure after myocardial infarction.

BACKGROUND Remote ischemic conditioning (RIC) by repeated treatment of transient limb ischemia is a clinically applicable method for protecting the heart against injury at the time of reperfusion. In this study, we investigated the effects of repeated RIC on cardiac dysfunction after myocardial infarction (MI). METHODS AND RESULTS At 4weeks after MI, rats were separated into the untreated (UT) group or the RIC-treated group. RIC treatment was performed by 5cycles of 5min of bilateral hindlimb ischemia and 5min of reperfusion once a day for 4weeks. Despite comparable MI size, left ventricular (LV) ejection fraction (LVEF) was significantly improved in the RIC group compared with the UT group. Furthermore, the LVEF in the RIC group was improved, although not significantly, after treatment. RIC treatment also prevented the deterioration of LV diastolic function. MI-induced LV interstitial fibrosis in the boundary region and oxidant stress were significantly attenuated by RIC treatment. MicroRNA-29a (miR-29a), a key regulator of tissue fibrosis, was highly expressed in the exosomes and the marginal area of the RIC group. Even in the differentiated C2C12-derived exosomes, miR-29a expression was significantly increased under hypoxic condition. As well as miR-29a, insulin-like growth factor 1 receptor (IGF-1R) was highly expressed both in the exosomes and remote non-infarcted myocardium of the RIC group. IGF-1R expression was also increased in the C2C12-derived exosomes under hypoxic conditions. CONCLUSIONS Repeated RIC reduces adverse LV remodeling and oxidative stress by MI. Exosome-mediated intercellular communication may contribute to the beneficial effect of RIC treatment.

Abnormal Regional Left Ventricular Systolic and Diastolic Function in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention: Clinical Significance of Post-Ischemic Diastolic Stunning

OBJECTIVES This study was designed to characterize both regional left ventricular (LV) systolic and diastolic function after percutaneous coronary intervention by using strain imaging (SI) derived from 2-dimensional speckle-tracking echocardiography. BACKGROUND Ischemic insult after coronary occlusion affects not only regional LV systolic but also diastolic function. METHODS Regional LV transverse peak strain and strain changes during the first one-third of diastole duration (strain imaging diastolic index [SI-DI]) were monitored in at-risk segments after percutaneous coronary intervention in 30 patients with coronary artery disease. The segments were divided into proximal and distal. Strain data in the at-risk segments were compared with values derived from remote nonischemic segments. RESULTS Coronary occlusion induced a marked reduction in the systolic strain in both proximal and distal at-risk segments (from 36.9 +/- 6.0% to 12.0 +/- 3.9% and from 31.9 +/- 5.6% to 6.2 +/- 3.3%, respectively, p < 0.0001). Concomitantly, SI-DI values decreased (from 76.6 +/- 5.3% to -21.2 +/- 9.1% and from 72.5 +/- 5.9% to -48.7 +/- 20.8%, respectively, p < 0.0001). Upon reperfusion, systolic deformation parameters returned to near-normal pre-occlusion values. However, SI-DI values in the both proximal and distal at-risk segments decreased (43.2 +/- 9.5%, p < 0.01, and -17.3 +/- 11.1%, p < 0.0001, respectively) 30 min after reperfusion and were still lower (51.5 +/- 9.9%, p < 0.01) in the distal at-risk segment 24 h after reperfusion. CONCLUSIONS SI analysis provides detailed mechanical characterization of regions with myocardial ischemic insult and can demonstrate post-ischemic diastolic stunning despite complete systolic functional recovery after reperfusion.