Abstract View largeDownload slide View largeDownload slide This editorial refers to ‘In vivo predictors of plaque erosion in patients with ST-segment elevation myocardial in farction: a clinical, angiographic, and intravascular optical coherence tomography study’†, by J. Dai et al., on page 2077. Plaque erosion occurs without cap disruption where flowing blood comes into direct contact with intimal surface lacking endothelial cells.1 In both clinical studies using intravascular imaging and autopsy data from subjects dying suddenly, plaque erosion is the second most common cause of coronary thrombus. In our recent pathological analysis of autopsies from subjects dying suddenly, plaque rupture was the most frequent causes of coronary thrombus (60%), the second most frequent was erosion (30%), and the third was calcified nodule (5%).2 The mechanisms leading to plaque erosion remain somewhat elusive, in part because of a lack of representative animal models as well as scarcity of in vivo data. Old imaging techniques such as coronary angiography or intravascular ultrasound lack the resolution needed to differentiate plaque rupture from erosion. The relatively recent introduction of optical coherence tomography (OCT), which measures backscattered light, or optical echoes, derived from an infrared light source directed at the arterial wall to generate higher resolution images of the order of 10–15 µM, has been instrumental in furthering our knowledge of in vivo assessment of coronary artery disease. Previous OCT studies of patients with acute coronary syndromes (ACS) showed a 27–31% prevalence of plaque erosion.3,4 Although consistent with the aforementioned pathological work, previous OCT studies consisted of a relatively small number of patients. Overall only eight studies have been performed to examine the prevalence of OCT-defined erosion, a total of 790 ACS patients (range 64–139 in each study), with the total number of cases with erosion 267 (range 25–37 in each study).3–11 With such a limited number of subjects with plaque erosion, one wonders about their applicability to the real world. In pathological series, patients with plaque erosion (a total of 148 patients) were younger, more likely to be female, have a history of smoking, and have lower cholesterol levels.11–13 Whether this is truly representative of patients coming to the clinic with ACS remains unknown, as does more detailed information about other risk factors. The study by Dai et al. in this issue of the journal represents the largest OCT study to date in patients presenting with ST-elevation myocardial infarction, all of whom had OCT imaging at the time of intervention.14 A total of 822 patients were suitable for culprit lesion evaluation by OCT, with plaque rupture accounting for 564 (69%) and plaque erosion for 209 (25%). The authors report similar findings to those which have been previously shown in autopsy studies. Overall Dai et al. also demonstrate that plaque erosion is more frequent in younger individuals, is more likely to occur in younger women (i.e. <50 years of age), and is more likely in current smokers. Subjects with plaque erosion had lower total cholesterol and LDL levels as compared with ruptures. Other coronary risk factors such as diabetes, hypertension, dyslipidaemia, and chronic kidney disease (CKD) were less common in erosion vs. rupture. The latter findings are novel, and help to expand our understanding of plaque erosion. Previous pathology analyses by Burke, Farb, Arbustini, and Yahagi were limited by the small number of subjects in each study, lacked detailed clinical data, and lacked statistical power to detect differences.2,11–13,15 Further. Dai et al. also found differences when examining specifically the culprit lesion. Plaque erosion lesions had a lower percentage of stenosis (64.4 ± 13.3%) and a larger minimal lumen area [(MLA) 1.8 mm2 (1.4–2.8 mm2)] as compared with plaque ruptures [68.6 ± 13.8%, MLA 1.6 mm2 (1.3–2.2 mm2)].14 Plaque erosion lesions had a lower prevalence of lipid-rich plaque, less lipid content, and less calcification, and more were frequently located near bifurcations as compared with plaque ruptures.14 Also, thin-cap fibroatheromas (TCFAs) were less frequently observed in erosion cases than in ruptures (14% vs. 90%; P < 0.001). Positive remodelling is considered the hallmark of rupture, while erosion cases more often demonstrate negative remodelling in pathological studies. Positive remodelling has been linked to higher inflammation in ruptures vs. erosion and this observation was confirmed in the study of Dai et al. Vessel size, however, was not reported. Although pathological studies have previously shown similar findings to those shown by Dai et al. in terms of plaque characteristics, the authors report on the importance of bifurcations as independent predictors of plaque erosion which may reveal important clues about its pathogenesis. In 2000, Tricot et al. reported that endothelial cell apoptosis was more frequently observed in the downstream parts of plaque where low flow and low shear stress prevail as compared with the upstream parts.16 Plaque erosion may localize preferentially in regions of low shear stress, and thus exhibit impaired endothelial antithrombotic properties, and occur in atheroprone locations. Recently, Franck et al. reported that flow disturbance, neutrophils, and Toll-like receptor 2 signalling play an important role in the mechanism of plaque erosion.17 Flow perturbation promotes neutrophil recruitment and thrombus formation, eventually leading to endothelial injury. Nakazawa et al. reported that plaque formation in native coronary bifurcations was significantly higher in low shear stress regions located in the lateral wall vs. high shear stress regions located at the carina.18 To understand fully the relationship between plaque erosion and shear, we would need to have more information about the percentage stenosis or lumen area in other locations besides the culprit site. These data were not provided. More erosion lesions occurred in the left anterior descending (LAD) artery as compared with ruptures (61% vs. 47%), while the opposite was true for the right coronary artery (RCA) (31% vs. 43%), and lesions in the left cicumflex (LCX) artery were equivalent (8% vs. 10%); P = 0.002. Both erosions and ruptures occur more frequently in the proximal and mid segments of the coronary arteries. Multivessel disease is more common in ruptures than in erosions (50% vs. 30%; P < 0.001). These are all characteristics that were also reported in pathological studies. However, the authors report that initial TIMI flow <1 was more frequent and mural thrombus was greater in ruptures vs. erosions (79% vs. 67%, P = 0.001 and 91 vs. 85%, P = 0.006, respectively). These differences do not reflect what is reported in pathology studies for distal emboli (71% vs. 42%; erosions vs. rupture), which are more frequent, with greater healing of the thrombus seen in erosions than in ruptures (88% vs. 54%; P < 0.0001).19,20 We also need to discuss briefly the limitations of this study. The concept of OCT-defined erosion is relatively new. OCT-defined erosion is defined and categorized according to the absence of fibrous cap disruption and the presence of thrombus, and divided into definite OCT-defined erosion and probable OCT-defined erosion.4 First, definite OCT-defined erosion is defined as the presence of a luminal thrombus overlying an intact and visualized plaque. Secondly, probable OCT-defined erosion is defined as (i) luminal surface irregularity at the culprit lesion in the absence of thrombus; or (ii) attenuation of underlying plaque by thrombus without superficial lipid or calcification immediately proximal or distal to the site of the thrombus.4 The limitations of OCT in this regard must be discussed. OCT cannot distinguish the presence or absence of endothelial cells on the plaque surface, and the presence of luminal thrombus hampers the penetration of light into the underlying plaque, making reliable measurements and diagnosis of the various causes of coronary thrombus difficult.21 In many of these cases, it is likely that thrombus still remained regardless of the use of an aspiration catheter, and this may have led to a misdiagnosis of erosion. Regarding probable OCT erosion, plaque erosion pathologically is not defined as the absence of lipid or calcification at the culprit site. The reason for this is that the underlying plaque is fibroatheroma, which may include lipid and is not necessarily lacking calcification (Take home figure). Thus, the accuracy of OCT to identify erosions remains uncertain and must be taken as an important caveat when interpreting this study. Take home figure View largeDownload slide Plaque erosion. (A and B) Plaque erosion with thrombus. There is a lack of disruption of fibrous cap and the thrombus is not in contact with the underlying lipid pool or necrotic core (A and B). Note that both the thrombi are in direct contact with the underlying smooth muscle cell within a proteoglycan-rich matrix (C and E). The underlying plaque shows the presence of a lipid pool (A and D) and a necrotic core with haemorrhage and fragment calcification (B and F). The PIT lesion shows the presence of superficial macrophages while the FA shows the focal presence of macrophages in areas around the necrotic core. Early organization is observed at the thrombus intimal interface, especially in (B). CA, calcium; FA, fibroatheroma; LP, lipid pool; NC, necrotic core; OT, organizing thrombus; PIT, pathological intimal thickening. Take home figure View largeDownload slide Plaque erosion. (A and B) Plaque erosion with thrombus. There is a lack of disruption of fibrous cap and the thrombus is not in contact with the underlying lipid pool or necrotic core (A and B). Note that both the thrombi are in direct contact with the underlying smooth muscle cell within a proteoglycan-rich matrix (C and E). The underlying plaque shows the presence of a lipid pool (A and D) and a necrotic core with haemorrhage and fragment calcification (B and F). The PIT lesion shows the presence of superficial macrophages while the FA shows the focal presence of macrophages in areas around the necrotic core. Early organization is observed at the thrombus intimal interface, especially in (B). CA, calcium; FA, fibroatheroma; LP, lipid pool; NC, necrotic core; OT, organizing thrombus; PIT, pathological intimal thickening. Despite these limitations, the data of Dai et al. generally lend credence to the idea that plaque erosion as a disease entity is wholly different from plaque rupture. Fundamental differences in the pathogenesis of thrombosis probably exist, and this raises important questions about the overall topic of therapeutic strategies to prevent coronary artery disease. A substantial number of coronary events result from plaque erosions, yet little is known of how to prevent such events from occurring. While statins are commonly used for primary and secondary prevention of coronary artery disease, does lipid lowering do anything to prevent plaque erosion events? Also, a small study of effective antithrombotic therapy without stenting has shown promise to stabilize plaques and therefore prevent future neoatherosclerosis within stents, thus raising our confidence that innovative therapies are possible in patients with plaque erosion.22 However, we need to determine in large prospective studies what are the proper preventative treatments for this entity. This and many other questions remain unanswered, but the work of Dai et al. shows that we are making progress in answering some of these questions. Conflict of interest: The CVPath Institute has received institutional research support from 480 Biomedical, Abbott Vascular, ART, BioSensors International, Biotronik, Boston Scientific, Celonova, Claret Medical, Cook Medical, Cordis, Edwards Lifescience, Medtronic, MicroPort, MicroVention, Celonova, OrbusNeich, ReCore, SINO Medical Technology, Spectranetics, Surmodics, Terumo Corporation, W.L. Gore, and Xeltis. R.V. has received honoraria from 480 Biomedical, Abbott Vascular, Boston Scientific, Cook Medical, Lutonix, Medtronic, Terumo Corporation, and W.L. Gore; and is a consultant for 480 Biomedical, Abbott Vascular, Medtronic, and W.L. Gore. A.V.F. has sponsored research agreements with Boston Scientific and Medtronic CardioVascular, and is an advisory board member to Medtronic CardioVascular. H.J. reports no conflicts of interest. References 1 Falk E , Nakano M , Bentzon JF , Finn AV , Virmani R. Update on acute coronary syndromes: the pathologists’ view . Eur Heart J 2013 ; 34 : 719 – 728 . Google Scholar CrossRef Search ADS PubMed 2 Yahagi K , Davis HR , Arbustini E , Virmani R. Sex differences in coronary artery disease: pathological observations . Atherosclerosis 2015 ; 239 : 260 – 267 . Google Scholar CrossRef Search ADS PubMed 3 Higuma T , Soeda T , Abe N , Yamada M , Yokoyama H , Shibutani S , Vergallo R , Minami Y , Ong DS , Lee H , Okumura K , Jang IK. 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European Heart Journal – Oxford University Press
Published: Mar 13, 2018
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