Imaging of the vulnerable plaque: noninvasive and invasive techniques

In a large proportion of previously asymptomatic individuals, sudden coronary death or acute myocardial infarction occurs as the first manifestation of coronary atherosclerosis. Imaging of coronary atheromatous plaques has traditionally centered on assessing the degree of luminal stenosis. The angiographic techniques that are routinely used to identify stenotic atherosclerotic lesions are unable to identify high-risk plaques; plaques prone to rupture and cause a cardiovascular event. This is partly due to the fact that the majority of culprit lesions that produce acute cardiovascular syndromes are not severely stenotic, possibly due to significant positive remodeling and reduced protective collateral circulation as well as because the risk of plaque rupture is more closely related to plaque content than plaque size. Recently, the focus of new imaging techniques is to identify the high risk plaques; the "vulnerable plaques." In this review, we will refer to the noninvasive and invasive techniques that can detect the vulnerable plaque.     

内皮祖细胞在动脉粥样硬化易损斑块中的作用

目的 动脉粥样硬化易损斑块是急性冠状动脉综合征和心脏缺血性猝死的重要病理基础.研究证实易损斑块表面大面积内皮细胞受损和血栓形成,内皮受损后可引起炎症因子瀑布样反应、单核细胞浸润和血管平滑肌细胞增生,进而促发动脉粥样硬化易损班块形成,故修复受损血管内皮、促使血管重新内皮化已经成为防止动脉粥样硬化的重要课题.近年研究认为,...     

Techniques characterizing the coronary atherosclerotic plaque: influence on clinical decision making?

The composition of the atherosclerotic lesion rather than the degree of stenosis is currently considered to be the most important determinant for acute clinical events. Modalities capable of characterizing the atherosclerotic lesion may be helpful in understanding its natural history and detecting lesions with high risk for acute events. Speaking grossly, three histologic features of the vulnerable plaque have been reported: size of the atheroma, thickness of the fibrous cap, and inflammation. Imaging techniques are currently being deployed and are under development to aid visualization of the vulnerable coronary plaque. Most of these diagnostic modalities have the potential to detect locally one or more of the three histologically defined features of vulnerable plaque. This review will focus on imaging techniques that have been developed to characterize the atherosclerotic lesion. Most catheter-based visualization techniques will provide insight into components of the local atherosclerotic plaque which may limit their predictive value for the occurrence of a clinical event. Therefore, the clinical relevance of these imaging tools will be discussed.     

The vulnerable plaque: Current concepts and future perspectives on coronary morphology,composition and wall stress imaging

Cardiovascular imaging plays an important role in the identification and characterization of the vulnerable plaque. A major goal is the ability to identify individuals at risk of plaque rupture and developing an acute coronary syndrome. Early recognition of rupture‐prone atherosclerotic plaques may lead to the development of pharmacologic and interventional strategies to reduce acute coronary events.We review state‐of‐the‐art cardiovascular imaging for identification of the vulnerable plaque. There is ample evidence of a close relationship between plaque morphology and patient outcome, but molecular imaging can add significant information on tissue characterization, inflammation and subclinical thrombosis. Additionally, identifying arterial wall exposed to high shear stress may further identify rupture‐prone arterial segments. These new modalities may help reduce the individual, social and economic burden of cardiovascular disease.     

Imaging of atherosclerosis. Intravascular imaging of the vulnerable atherosclerotic plaque: spotlight on temperature measurement

The vulnerable atherosclerotic plaque is associated with an increased number of acute coronary syndromes. Current techniques such as coronary angiography are unable to detect and prospectively evaluate these lesions. Recently, other techniques, both invasive and noninvasive, are being developed trying to detect the plaque that is at increased risk for rupture eventually resulting in increased thrombosis. This review describes briefly evolving techniques for imaging of vulnerable plaques and describes in detail intravascular thermography.     

动脉粥样斑块破裂的研究进展

急性冠状动脉综合征发生的主要病理生理机制系粥样斑块破裂。因此 ,研究斑块破裂的机制及探索稳定斑块的方法具有重要临床意义。本文综合现有文献 ,就粥样斑块的形成、分类及其新的认识 ,斑块破裂的方式 ,斑块破裂的影响因素 ,斑块破裂的模型复制及其预测方法 ,斑块破裂的防治现状作一概述 ,并提出急性冠状动脉综合征以稳定易破斑块为重点。     

稳定斑块——治疗急性冠状动脉综合征的新策略

急性冠状动脉综合征主要由于不稳定的冠状动脉粥样硬化斑块受侵蚀或破裂继发血栓引起。不稳定斑块的特征包括巨大的脂核、炎症细胞和炎症介质的增多以及较薄的纤维帽。对此进行干预可望达到稳定斑块的目的,从而给急性冠状动脉综合征的防治带来新的前景。     

光学相干断层成像在检测易损斑块中的应用价值

冠状动脉粥样硬化斑块易发斑块破裂,导致急性冠状动脉综合征,引起急性心肌梗死。有效的评价斑块的结构及成份特点,监测其演变过程,对选择治疗时机和治疗方案有重要意义。光学相干断层成像是一种新型的生物医学成像技术,它可以对易损斑块准确识别。现就光学相干断层成像在检测易损斑块中的应用价值作一综述。     

Vulnerable plaque: the challenge to identify and treat it

In order to understand, treat, and prevent acute coronary syndromes we need to improve our ability to identify the rupture-prone, vulnerable atherosclerotic coronary plaque. The diagnostic modalities that are currently available to clinical practice have not fulfilled this expectation, and newer diagnostic techniques based on the recently identified features of the vulnerable plaque are quite promising. Coronary angiography, intravascular ultrasound, and angioscopy have been used in the clinical arena of interventional cardiology with several limitations regarding the identification of the vulnerable plaque. Thermography, optical coherence tomography, elastography, Raman spectroscopy, and infrared spectroscopy are used in clinical trials and the results are encouraging. Ultrafast computed tomography and magnetic resonance imaging have the advantage of being noninvasive. With our progress in the identification of the rupture-prone vulnerable coronary plaque, we will be able to identify patients that are at high risk and will benefit from a more aggressive therapeutic approach.     

Pathogenesis of Acute Ischemic Coronary Syndromes

Understanding of the pathogenesis of acute ischemic coronary syndromes has lead to the development of novel diagnostic and therapeutic modalities offering the possibility of improved clinical outcomes. This article details the importance of the vulnerable atherosclerotic plaque, invlammaiton and plaque rupture and thronbosis in the development of the clinical manifestations of an acute ischemic coronary syndrome.     

Photodynamic therapy for the treatment of atherosclerotic plaque: Lost in translation?

Acute coronary syndrome is a life‐threatening condition of utmost clinical importance, which, despite recent progress in the field, is still associated with high morbidity and mortality. Acute coronary syndrome results from a rupture or erosion of vulnerable atherosclerotic plaque with secondary platelet activation and thrombus formation, which leads to partial or complete luminal obstruction of a coronary artery. During the last decade, scientific evidence demonstrated that when an acute coronary event occurs, several nonculprit plaques are in a “vulnerable” state. Among the promising approaches, several investigations provided evidence of photodynamic therapy (PDT)‐induced stabilization and regression of atherosclerotic plaque. Significant development of PDT strategies improved its therapeutic outcome. This review addresses PDT's pertinence and major problems/challenges toward its translation to a clinical reality.     

Pathophysiological bases of unstable coronary syndrome

BACKGROUND: The acute coronary syndrome is the manifestation of a plaque rupture in a coronary artery, which can lead to intermittent or prolonged regional myocardial ischemia. In such a situation, the underlying atherosclerotic lesion is a complex one. Moreover, the mechanisms leading to the instability of an atherosclerotic plaque are complex themselves. This makes it problematic to systematically analyze the nature of the acute coronary syndrome. Moreover, no animal model is available to study this process. PATHOMORPHOLOGICAL AND CLINICAL STUDIES: Substantial insights into the basis of the acute coronary syndrome have been gathered by pathomorphological analyses, which have helped to identify a number of criteria describing a vulnerable plaque. Clinical studies have helped to identify the thrombotic component as an important aspect of the clinical manifestation of the acute coronary syndrome. Based on such data, well-defined antithrombotic strategies play an important role in today's therapy of the acute coronary syndrome. TRIGGERING MECHANISMS: Concerning the triggering mechanisms for an acute coronary syndrome, there is a number of suspected processes, the most important of which is local inflammation of the coronary plaque. Inflammatory processes have recently been recognized as important stimulators of vascular modeling during atherogenesis. These inflammatory mechanisms involve a number of different cytokines, cells of the immune system and other components of the immune systems such as the complement cascade. C-reactive protein may even be a link between systemic and local inflammatory processes, because it has been shown to be systemically elevated in patients with unstable angina, and--most recently--has been shown to be involved in the initiation and progression of early atherosclerotic lesions. Local inflammation of the atherosclerotic plaques induces the expression of a number of growth factors and other potent molecules that contribute to vascular remodeling. These substances are acting on smooth muscle cells, fibroblasts as well as on the extracellular matrix and include growth factors, matrixmetalloproteinases and tissue inhibitors of metalloproteinase. Another component of potential significance within the unstable plaque is the process called plaque-angiogenesis. Plaque-angiogenesis occurs within complicated atherosclerotic plaques, the process of angiogenesis leads to destabilization of the extracellular matrix and, moreover, newly formed capillaries are more likely to rupture and may therefore be an important trigger of plaque rupture and of the acute coronary syndrome. THERAPEUTIC APPROACHES: A number of molecular strategies including inhibition of matrix metalloproteinasis or inhibitors of angiogenesis may turn out to stabilize the vulnerable plaque. Until these therapeutic concepts may be used in the clinic, our therapeutic repertoire will mostly consist of antithrombotic and entire antiinflammatory approaches.     

微观结构在易损斑块进展中的作用

急性冠状动脉综合征常常导致严重的心血管事件,而冠状动脉粥样硬化斑块破裂是绝大多数急性冠状动脉综合征发生的原因,因此检测高破裂风险的易损斑块,对筛选和干预急性冠状动脉综合征具有重要意义。随着研究的不断进展,易损斑块内的一些微观结构如斑块内新生血管、微小钙化、胆固醇结晶,在易损斑块的进展中起到重要的作用。因此,本文以易损斑块内最常见的3种微观结构为重点,综述斑块内微观结构在易损斑块进展中的作用。     

Intracoronary Imaging in the Detection of Vulnerable Plaques

Coronary artery disease is the result of atherosclerotic changes to the coronary arterial wall, comprising endothelial dysfunction, vascular inflammation and deposition of lipid-rich macrophage foam cells. Certain high-risk atherosclerotic plaques are vulnerable to disruption, leading to rupture, thrombosis and the clinical sequelae of acute coronary syndrome. Though recognised as the gold standard for evaluating the presence, distribution and severity of atherosclerotic lesions, invasive coronary angiography is incapable of identifying non-stenotic, vulnerable plaques that are responsible for adverse cardiovascular events. The recognition of such limitations has impelled the development of intracoronary imaging technologies, including intravascular ultrasound, optical coherence tomography and near-infrared spectroscopy, which enable the detailed evaluation of the coronary wall and atherosclerotic plaques in clinical practice. This review discusses the present status of invasive imaging technologies; summarises up-to-date, evidence-based clinical guidelines; and addresses questions that remain unanswered with regard to the future of intracoronary plaque imaging.     

Plaque instability in peripheral vessels

Vulnerable atherosclerotic plaques, those that are prone to rupture, are soft and lipid rich. Other factors that contribute to destabilizing these plaques are inflammation and vasoconstriction. Although less information is available regarding noncoronary vulnerable plaques than the more frequently studied coronary plaques, it appears that the amount of soft lipid “gruel” as well as in situ inflammation plays a crucial role in destabilizing peripheral vascular atherosclerotic plaque, eventually causing its rupture. As in the coronary circulation, it is likely that the majority of acute plaque rupture events are clinically silent. Nevertheless, preventing plaque rupture in the noncoronary circulation is of the utmost importance because this is the presumed mechanism of progression of peripheral vascular atherosclerotic lesions. Copyright 2002, Elsevier Science (USA). All rights reserved.     

红细胞膜脂质与急性冠脉综合征斑块易损性的相关性研究

斑块的易损性是急性冠脉综合征主要病理生理机制。而斑块内出血和新生血管的形成在易损斑块的形成中起着重要的作用,这其中红细胞膜脂质可能发挥着巨大的作用,它们通过不同的机制使斑块从稳定发展为不稳定。     

Coronary artery imaging in the new millennium

Atherosclerotic disease and its thrombotic complications remain the leading causes of mortality and morbidity in Western society. In Australia, cardiovascular disease is responsible for one in every 2.4 (41%) deaths and is the leading single cause of mortality. The crucial final common process for the conversion of a non-occlusive, often clinically silent, atherosclerotic lesion to a potentially fatal condition is plaque disruption. The mortality associated with atherosclerotic disease relates to the acute coronary syndromes, including acute myocardial infarction, unstable angina pectoris and sudden cardiac death. There is substantial clinical, experimental and postmortem evidence demonstrating the role acute thrombosis upon a disrupted atherosclerotic plaque plays in the onset of acute coronary syndromes. Atherosclerotic plaque composition, rather than the stenotic severity, appears to be central in determining risk of both plaque rupture and subsequent thrombogenicity. In particular, a large lipid core and a thin fibrous cap render an atherosclerotic lesion susceptible or vulnerable to these complications. We are currently limited in our ability to accurately identify patients at risk for an acute coronary event. The armamentarium of diagnostic investigations, both non-invasive and invasive, currently clinically available is only able to provide us with data related to the stenotic severity of a coronary artery. The non-invasive testing includes stress-induced (exercise or pharmacological) ischaemic changes in electrical repolarisation, wall motion or myocardial radioactive-tracer uptake. The invasive test of coronary angiography, although the current 'gold standard' for the detection of coronary atherosclerotic disease, provides us with no data about the composition of the atherosclerotic lesion. However, the vast majority of acute coronary events involve a non-critically stenosed atherosclerotic lesion, and thus with currently available means of identification, these lesions would be undetected by stress testing/imaging techniques. Given the critical role that atherosclerotic lesion composition has been shown to play in the risk of both plaque rupture and subsequent thrombogenicity and, consequently, an acute coronary event, new detection techniques need to be investigated for the task of documenting atherosclerotic lesion composition. In the present review we will focus on the status of imaging modalities available for coronary artery imaging and how they may advance our understanding and management of patients with and at risk of coronary artery disease in the new millennium.     

Technology Insight: optical coherence tomography--current status and future development

The understanding of concepts in coronary artery disease, such as the vulnerable or high-risk plaque, which accounts for many acute coronary events arising from non-flow-limiting coronary lesions, has advanced remarkably. Although coronary angiography is an established imaging technique for visualizing atherosclerotic disease, it is limited by its two-dimensional imaging aspect and a low sensitivity for identifying lesions in the presence of positive remodeling and diffuse disease. Moreover, coronary atherosclerotic plaques cannot be characterized. Although intravascular ultrasound is currently the most commonly employed adjunctive method to better define lesions, it is limited by low resolution. The development of new technologies for improved coronary plaque characterization has, thus, been desired. Optical coherence tomography is a developing technique that uses near-infrared light for the cross-sectional visualization of the vessel wall at the microscopic level. It enables excellent resolution of coronary architecture and precise characterization of plaque architecture. Quantification of macrophages within the plaque is also possible. These capabilities allow precise identification of the most common type of vulnerable plaque, the thin-cap fibroatheroma. Here, we discuss results from clinical studies which indicate that optical coherence tomography is a promising imaging technique for improved characterization of the coronary atherosclerotic plaque.     

Strategies to achieve coronary arterial plaque stabilization.

Acute coronary syndromes result from fissure, erosion or rupture of a vulnerable atherosclerotic plaque. The characteristics of a vulnerable plaque include a large lipid pool, an abundance of inflammatory cells and mediators, a reduced smooth muscle cell and collagen content and a thin overlying fibrous cap. Potential therapeutic strategies at achieving plaque stabilization have targeted these features. Lipid lowering agents, beta-adrenergic blockers, angiotensin converting enzyme inhibitors and antioxidants have been shown to reduce the incidence of acute coronary syndromes, presumably through plaque stabilization. Matrix metalloproteinase inhibitors as well as macrolide antibiotics and gene therapy approaches show promise in achieving plaque stabilization. The evidence supporting plaque stabilization by these agents and the mechanisms by which these agents stabilize plaques are discussed in detail in this review.