Pathophysiology of acute coronary syndrome

This article reviews the current understanding of the pathophysiology of acute coronary syndrome and how these concepts have altered our clinical approach to the acute phase of coronary heart disease. Thrombosis due to erosion or, in most cases, rupture of a vulnerable atherosclerotic plaque underlies most acute coronary syndromes. The protective fibrous cap undergoes degradative processes controlled by inflammatory mediators that break down the interstitial collagen within the fibrous cap. Thrombus formation depends on factors in the solid-phase of the ruptured plaque as well as on fluid-phase determinants in blood. Depending on the degree of thrombus formation the subsequent obstruction of the coronary artery is followed clinically by unstable angina, non-ST- and ST-segment elevation myocardial infarction.     

Atherosclerosis]

Atherosclerosis is vascular disease characterized by thickening, hardening, and remodelling of the arterial wall. Occlusive vascular disease most often results from thrombosis superimposed on atherosclerotic plaque. Lipoproteins enter the vessel wall, promoting the recruitment of monocytes, which imbibe lipids and become foam cells. Smooth muscle cells invade these early plaques, producing connective tissue fibrils that form a fibrous cap over the lipid center; rupture of this cap is an important cause of thrombosis. The specific topography of early atherosclerotic lesions is primarily attributed to wall shear stress, one of hemodynamic forces. Inflammatory mediators regulate processes that determine the composition of the plaque's fibrous cap, a structure that separates blood from the thrombogenic lipid core. Factors involved in coagulation, such as thrombin, can regulate non-thrombotic functions of vascular wall cells such as smooth muscle proliferation or cytokine release. Tissue factor is a major regulator of coagulation and hemostasis. When the plaques are ruptured or eroded, exposure of cellular and extracellular tissue factor to circulating blood play a pivotal role in mediating fibrin-rich thrombus formation leading to acute coronary syndromes. Several serial angiographic studies have demonstrated that over 70% of acute coronary syndromes evolve from mildly to moderately obstructive atherosclerotic plaques.     

Measurement of oxidized LDL and its soluble receptors

Oxidized LDL and its receptors play important roles in atherosclerotic progression and atherosclerotic plaque rupture, by enlarging the lipid core and weakening the fibrous cap. Oxidized LDL, in fact, induces foam cell transformation of macrophages, production of matrix metalloproteinases(MMPs), and apoptosis of smooth muscle cells. Oxidized LDL concentrations in circulating blood in humans have been shown to be elevated in diabetes and atherosclerotic vascular diseases, especially acute coronary syndrome. Lectin-like oxidized LDL receptor-1(LOX-1) is a cell surface receptor for oxidized LDL, which is abundantly expressed in atherosclerotic plaques and is involved in oxidized LDL-induced MMP production and apoptosis. Soluble LOX-1 concentration in human blood also have been shown to be elevated in coronary heart diseases especially in acute coronary syndrome.     

Acute coronary syndrome diagnosed by the intravascular imaging

Coronary plaque rupture and the following formed thrombus have been revealed the cause of acute coronary syndrome. This evidence had been proposed by the pathologists 100 years ago; however, the intravascular imaging such as intravascular ultrasound (IVUS) or coronary angioscopy has revealed the clinical evidences in live human being. Thrombus and yellow plaque detected by coronary angioscopy as well as the ruptured fibrous cap detected by IVUS are the characteristics for the lesion of ACS, which does not show the significant stenosis. Thus, ACS lesion should be diagnosed by IVUS or coronary angioscopy.     

Optical Coherence Tomography and Fibrous Cap Characterization

The pathophysiology of acute coronary syndromes has long been associated with atherosclerotic plaque rupture. Inflammation, thinning, and disruption of the fibrous cap have been implicated with the final processes leading to plaque rupture, but confirmation of these mechanisms of coronary thrombosis in humans has been hampered by the lack of imaging methods with sufficient resolution to resolve fibrous cap characterization and thickness in vivo. Intravascular optical coherence tomography (OCT) provides images with micron-level axial and lateral resolution, enabling detailed visualization of micro-structural changes of the arterial wall. The present article provides an overview of the potential role of OCT in identifying and characterizing fibrous cap morphology, thickness, and inflammation in human coronary plaques.     

What pathological components indicate carotid atheroma activity and can these be identified reliably using ultrasound?

OBJECTIVE: The aim of this project was to determine whether histological features of 'active' plaque as described in the coronary circulation following acute myocardial infarction were similar in the carotid circulation, and whether these factors could be detected ultrasonically. METHOD: Endarterectomy specimens were prospectively collected, and examined histologically and assessed by two observers for ulceration, inflammation, size of necrotic core, thickness of fibrous cap, haemorrhage and luminal thrombosis. Ultrasound of the plaque obtained preoperatively was similarly coded (blind to pathology) and compared with the pathology. RESULTS: In 42 endarterectomy specimens, there was a highly significant relationship between a thin fibrous cap and a large necrotic core (P<0.002), irregular plaque contour (P<0.05) and ulceration (P<0.01) and between a large necrotic core (P<0.002) and ulceration and inflammation (P<0.05). Increasing amounts of necrosis were associated with more surface thrombosis (P<0.02). Ultrasound detected the thickness of the fibrous cap and 'any necrosis or haemorrhage' with some reliability (kappas are 0.53 and 0.5, respectively), but not ulceration, necrosis or haemorrhage on their own. CONCLUSION: Features corresponding to active atheromatous plaque are similar in the carotid and coronary arteries, and some of these, namely lucent areas in the plaque (corresponding to necrosis or haemorrhage) and the thickness of the fibrous cap, can be determined reliably with ultrasound.     

血清脂蛋白相关磷脂酶A2与冠状动脉粥样硬化斑块稳定性的相关研究——附107例报告

目的：探讨血清脂蛋白相关磷脂酶A2（lipoprotein—associated phospholipase A2,Lp-PLA2）水平与冠状动脉粥样硬化斑块稳定性的关系。方法：对107例冠状动脉粥样硬化性心脏病（冠心病）患者行冠状动脉造影（coronary angiography,CAG）和血管内超声（intravascular ultrasound,IVUS）检查,根据CAG和IVUS检查有无冠状动脉改变及斑块性质将患者分为稳定斑块组（38例）、不稳定斑块组（33例）和无疯块组（36例）,检测所有患者血清的Lp—PLA2水平,分析血清Lp-PLA2水平与IVUS检查指标包括纤维帽厚度、偏心指数、重构指数的相关性。结果：稳定斑块组和不稳定斑块组的血清Lp-PLA2水平明显高于无斑块组（P〈0．05）;不稳定斑块组的血清Lp-PLA2高于稳定斑块组（P〈0．05）。血清Lp-PLA2与斑块纤维帽厚度无明显相关性（r=-0．31,P〉0．05）,但与偏心指数和重构指数呈正相关（r=0．79,P〈0．01;r=0．62,P〈0．05）。结论：冠心病患者血清Lp-PLA2水平与冠状动脉粥样硬化斑块稳定性有关,可作为临床预测不稳定斑块的血清学指标。     

颈动脉内中膜厚度结合血清MMP-9及APN预测冠状动脉斑块稳定性

目的 探讨颈动脉内-中膜厚度(CIMT)、血清脂联素(APN)、血清基质金属蛋白酶-9(MMP-9)诊断冠状动脉不稳定斑块的价值。方法 选取接受OCT检查的急性冠状动脉综合征(ACS)患者27例(ACS组),并选取同期来诊的急性胸闷、胸痛而冠状动脉造影阴性者30例为对照组。检测血清APN及MMP-9,并行颈动脉超声检查,并记录CIMT、APN、MMP-9和冠状动脉斑块纤维帽厚度;分析两组指标的差异及各指标之间的相关性,绘制ROC曲线评价各指标对薄纤维帽斑块的诊断价值。结果 ACS患者CIMT、MMP-9水平显著高于正常组(P<0.01),而APN水平显著低于正常组(P<0.01);冠状动脉斑块纤维帽厚度与CIMT及MMP-9呈负相关(r=-0.357,P<0.05;r=-0.477,P<0.01),与APN呈正相关(r=0.468,P<0.05);CIMT、MMP-9、APN联合检测诊断冠状动脉薄纤维帽斑块的ROC曲线下面积大于单个指标的曲线下面积(分别为:0.815、0.688、0.772、0.739)。结论 CIMT值及MMP-9水平升高、APN水平降低与冠状动脉斑块的稳定性密切相关,且三者联合对ACS更具诊断价值。     

冠状动脉不稳定斑块的血管内超声影像分析

目的　探讨血管内超声 (intravascularultrasound ,IVUS)判定不稳定斑块的敏感性及特异性。方法　 43例确诊冠心病患者在冠状动脉造影 (coronaryangiography ,CAG)后行IVUS检查 ,根据斑块回声强弱分为软斑块组和硬斑块组 ,两组分别进行定量测定。结果　急性冠状动脉综合征者IVUS检出软斑块 2 2例 (2 2 /2 7) ,占 81.4% ,IVUS检测不稳定斑块的敏感性 81.4% ,特异性 75.0 % ,准确性 79.1% ,阳性预测值 84.6%。软斑块组脂核面积比硬斑块组的无回声区面积明显增大 (P <0 .0 1) ;脂核与斑块比软斑块组明显大于硬斑块组 (2 6.4%± 11.5%对 12 .0 %± 7.0 % ,P <0 .0 1) ;软斑块组纤维帽厚度明显小于硬斑块组 [(0 .3 8± 0 .14 )mm对 (1.17± 0 .3 6)mm ,P <0 .0 1] ;在面积狭窄率上 ,软斑块组明显小于硬斑块组 (62 .6%± 6.9%对 70 .9%± 7.5% ,P <0 .0 1) ;偏心程度软斑块组明显大于硬斑块组 (92 .9%对82 .4% )。两组间斑块大小差异无显著性意义 [(10 .70± 2 .96)mm2 对 (10 .84± 3 .48)mm2 ,P >0 .0 5]。结论　IVUS对冠状动脉不稳定斑块的判定具有较高的敏感性和特异性     

Current status and perspectives of coronary imaging for patients with diabetes mellitus

Diabetes mellitus (DM) is an independent and distinct risk factor of ischemic heart disease. Therefore, early identification and management of coronary atherosclerosis for patients with DM is being desired. For the purpose of visualizing coronary atherosclerosis, various imaging modalities have been proposed especially to identify an unstable plaque that has a thin fibrous cap and a large lipid core. These modalities include intravascular ultrasound, coronary angioscopy, intracoronary thermography, optical coherence tomography, multi-slice CT, MRI, and so on. The development of these modalities are now pushing all cardiologists to get interested in a new field called as "plaque imaging".     

Fusion of fibrous cap thickness and wall shear stress to assess plaque vulnerability in coronary arteries: a pilot study

Purpose

Identification of rupture-prone plaques in coronary arteries is a major clinical challenge. Fibrous cap thickness and wall shear stress are two relevant image-based risk factors, but these two parameters are generally computed and analyzed separately. Accordingly, combining these two parameters can potentially improve the identification of at-risk regions. Therefore, the purpose of this study is to investigate the feasibility of the fusion of wall shear stress and fibrous cap thickness of coronary arteries in patient data.

Methods

Fourteen patients were included in this pilot study. Imaging of the coronary arteries was performed with optical coherence tomography and with angiography. Fibrous cap thickness was automatically quantified from optical coherence tomography pullbacks using a contour segmentation approach based on fast marching. Wall shear stress was computed by applying computational fluid dynamics on the 3D volume reconstructed from two angiograms. The two parameters then were co-registered using anatomical landmarks such as side branches.

Results

The two image modalities were successfully co-registered, with a mean (±SD) error corresponding to \(8.6\,\pm \,6.7\,\%\) of the length of the analyzed region. For all the analyzed participants, the average thinnest portion of each fibrous cap was \(129\,\pm \,69\,\upmu \text {m}\), and the average WSS value at the location of the fibrous cap was \(1.46\,\pm \,1.16\,\text {Pa}\). A unique index was finally generated for each patient via the fusion of fibrous cap thickness and wall shear stress measurements, to translate all the measured parameters into a single risk map.

Conclusion

The introduced risk map integrates two complementary parameters and has potential to provide valuable information about plaque vulnerability.

     

A review in enormity of OCT and its enduring understanding of vulnerable plaque in coronary bifurcation lesion

Optical coherence tomography (OCT) has emerged as one of the most promising tools to assist the optimization of percutaneous coronary intervention (PCI). Its ability to provide unique information on the plaque at high risk for rupture, plaque composition, the thickness of the fibrous cap, the presence of macrophage and thrombi has not only assisted simple PCI but also in many complex bifurcation lesions PCI. OCT has helped to provide valuable anatomic information to optimize stent implantation and adapt PCI strategy in individual patients. This review article summarizes the current role of OCT as an imaging technology and prediction of vulnerable plaque, its site and composition at the coronary bifurcation lesions for supporting the clinical decision.     

Vulnerable plaque: detection and management

Because most myocardial infarctions result from the rupture of a plaque that did not significantly compromise the coronary lumen before the event, experts widely accept that the morphology, composition, and degree of inflammation of a coronary atherosclerotic plaque is more important than the degree of luminal stenosis. Two depicting examples are the concentric, calcified lesion that shows significant luminal stenosis but is stable because of the stabilizing clasp of calcification. In contrast, a smaller but inflamed thin fibrous cap atheroma with a big lipid/necrotic core may rupture and cause an immediate fatal coronary occlusion.     

Use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in patients with acute coronary syndrome

Renin-angiotensin system is well known that it plays an important role in the initiation and amplification of atherosclerosis that lead to cardiovascular disease. Angiotensin II is deeply involved in vasoconstriction, oxidative stress, inflammation, thrombosis, vascular remodeling, and sympathetic nerve activity. Many studies have documented the favorable effects of angiotensin converting enzyme inhibitor(ACE-I) and angiotensin receptor blocker(ARB) on cardiovascular disease in basic and clinical trials. Now accumulated evidences suggest ACE-I and ARB potentially prevent coronary plaque rapture, thrombosis and myocardial remodeling with acute coronary syndrome (ACS). ACS is occurred from plaque rupture on mild to moderate coronary atherosclerosis. Therefore, on treatment of ACS, it is important to prevent the plaque rupture and thrombosis by pharmacological intervention with ACE-I and ARB than coronary artery intervention which is down stream therapy for coronary artery stenosis.     

三维薄块多层重叠技术识别颈动脉粥样硬化斑块稳定性的临床研究

目的　探讨采用三维 (3D)薄块多层重叠技术 (multipleoverlappingthinslabangiography,MOTSA)检查颈动脉粥样硬化斑块稳定性的影像学特征及不稳定性斑块与缺血性卒中的关系。方法　对 4 0例明确为颈内动脉系统缺血性卒中急性期病例 (A组 )和 2 5例明确在 3个月内无颈内动脉系统缺血性卒中病例 (B组 )的颈动脉进行 3DMOTSA检查 ,将发现的粥样斑块按纤维帽特征分型。结果　 3DMOTSA检查发现 4 1例患者存在粥样斑块 ,纤维帽厚型、薄型及破裂型分别为 19、14、8例 ,A组4 5 %为不稳定斑块 (薄型和破裂型纤维帽 ) ,B组 16 %为不稳定斑块 ,两组比较差别有显著性 (P <0 0 1)。结论　 3DMOTSA检查可识别颈动脉内覆盖在脂质核上的纤维帽 ,不稳定斑块脱落可能与近期缺血性卒中有关。     

Vessel wall apoptosis and atherosclerotic plaque instability

Atherosclerotic cardiovascular disease remains the leading cause of death in the industrialized world. Most cardiovascular deaths result from acute coronary syndromes, including unstable angina pectoris and acute myocardial infarction. Coronary syndromes often arise from acute coronary thrombosis, itself commonly a result of disruption or rupture of the fibrous cap of a lipid-laden atherosclerotic plaque. Despite this huge clinical burden of atherosclerotic plaque instability, our understanding of the molecular mechanisms mediating atherosclerotic plaque disruption and rupture, at a cellular level, remains limited. Placed in a clinical context, this review discusses our current understanding of the molecular basis for atherosclerotic plaque instability, with particular emphasis on the process of apoptosis-or programmed cell death-seen increasingly as playing a key role in a number of cell types within the vessel wall.     

Present-day investigations cannot adequately determine the risk of acute coronary syndromes

It is an important irony that present-day clinical stress testing methods including exercise electrocardiogram, stress echocardiography and even coronary angiography are not able to demonstrate vulnerable coronary plaques at risk of rupture. A vulnerable plaque may in fact be invisible on clinical stress test and perhaps only visualized directly through less available techniques such as coronary angioscopy. Landmark pathological studies have deepened our understanding of the mechanisms behind acute coronary syndromes over the last decade. Thrombosis plays a key role and is a unifying feature in the pathogenesis. Platelet-rich thrombus superimposed over the disrupted atherosclerotic plaque or eroded plaque endothelium, with or without fibrin-thrombus extension, is evident in post-mortem necropsy and angioscopic studies. However features which contribute to the risk of acute events lie in the atherosclerotic plaque itself. Plaque content and not plaque size is the important factor. Clinical stress testing demonstrates plaque size but not plaque content. A plaque will be prone to rupture if it has only a thin cap and a proportionally larger lipid core. In such a plaque there is preponderance of activated macrophages and T-lymphocytes, and high activity of matrix metalloproteinases. Smooth muscle cell proliferation and collagen synthesis are downregulated. These features may serve as possible targets for devising clinical methods to detect plaques at risk or for reversing the risk in vulnerable plaques.     

Development of a 3 French Dual-Frequency Intravascular Ultrasound Catheter

Coronary plaque morphology, including plaque size and fibrous cap thickness, is thought to contribute to the risk of plaque rupture and future cardiac events. Dual-frequency intravascular ultrasound has been proposed as a possible technique to visualize both large-scale features and superficial detail of coronary plaque; however, it has not been found to be feasible within the constraints of a clinically functional intravascular ultrasound catheter. In this study, we describe the design and fabrication of a dual-frequency catheter using a bidirectional transducer stack with center frequencies of approximately 30 and 80?MHz. We describe how the high-frequency transducer achieves significantly improved axial and lateral resolution (16 and 120?µm, respectively, vs. 50 and 220?µm) at the expense of penetration depth. Finally, imaging of ex vivo human coronary artery segments reveals that the catheter can provide complementary images of the deeper arterial wall and superficial plaque features.     

Intravascular Photoacoustic Imaging: A New Tool for Vulnerable Plaque Identification

The vulnerable atherosclerotic plaque is believed to be at the root of the majority of acute coronary events. Even though the exact origins of plaque vulnerability remain elusive, the thin-cap fibroatheroma, characterized by a lipid-rich necrotic core covered by a thin fibrous cap, is considered to be the most prominent type of vulnerable plaque. No clinically available imaging technique can characterize atherosclerotic lesions to the extent needed to determine plaque vulnerability prognostically. Intravascular photoacoustic imaging (IVPA) has the potential to take a significant step in that direction by imaging both plaque structure and composition. IVPA is a natural extension of intravascular ultrasound that adds tissue type specificity to the images. IVPA utilizes the optical contrast provided by the differences in the absorption spectra of plaque components to image composition. Its capability to image lipids in human coronary atherosclerosis has been shown extensively ex vivo and has recently been translated to an in vivo animal model. Other disease markers that have been successfully targeted are calcium and inflammatory markers, such as macrophages and matrix metalloproteinase; the latter two through application of exogenous contrast agents. By simultaneously displaying plaque morphology and composition, IVPA can provide a powerful prognostic marker for disease progression, and as such has the potential to transform the current practice in percutaneous coronary intervention.     

Identification of vulnerable atherosclerotic plaques

There has been great interest in the possibility of identifying plaques that might be the site of future acute coronary events. These plaques are termed vulnerable and the majority are lipid-rich with an abundance of inflammatory cells and a thin fibrous cap. Several techniques developed to identify these plaques are in various stages of development and in the near future, one might employ a strategy to potentially identify and therapeutically modify such lesions during percutaneous intervention to avoid future acute events. Although this approach of identifying the vulnerable plaque seems promising, there are significant potential limitations. The natural history of a vulnerable plaque is unknown and clinical trials utilizing this strategy of identification and therapeutic intervention are lacking. Moreover, in any given patient, multiple vulnerable plaques are likely to be present. This article reviews some of the techniques for identifying a vulnerable plaque and discusses the potential advantages and limitations of this strategy.