Editorials
No Epicardial Fat, No Plaque Rupture
2020 Volume 84 Issue 5 Pages 702-703
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2020 Volume 84 Issue 5 Pages 702-703
Plaque rupture is the primary mechanism of coronary thrombosis causing myocardial infarction and sudden cardiac death. The pathology of a ruptured plaque consists of a necrotic core with an overlying disrupted thin fibrous cap.1 Previous pathologic and clinical studies have consistently shown that plaque rupture occurs mainly in the proximal site of a coronary artery, especially in the left anterior descending artery (LAD).2 Structural stress of plaque in the proximal site of the coronary artery was believed to be one of the reasons for the nonuniform distribution of plaque rupture, because higher levels of structural stress could disrupt the fibrous cap.3 However, there may be other mechanisms because the “plaque structural stress” hypothesis cannot fully explain why plaque rupture in the right coronary artery (RCA) is most common in not only the proximal but also the mid segment.2,4
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In this issue of the Journal, Ito et al5 shed light on the mechanism of nonuniform distribution of plaque rupture, showing an association of local inflammation in epicardial adipose tissue (EAT) and coronary plaque progression via the vasa vasorum (VV). In this ex vivo study, LADs from 10 fresh cadavers of patients who had died of noncardiovascular causes were evaluated. The levels of inflammatory molecules from the adjacent EAT trimmed from the coronary artery were measured and the density of VV in the coronary artery was pathologically evaluated. The degree of inflammation in adjacent EAT was significantly higher in lipid-rich lesions than in lipid-poor lesions. In addition, adventitial VV was more prominent in the lipid-rich lesions compared with lipid-poor lesions, suggesting that EAT, together with inflammatory cells via VV, may play an important role in coronary plaque progression. Previous pathologic studies have demonstrated that the greatest amount of EAT is seen over the lateral right ventricular wall, followed by the anterior wall.6 Although EAT in the LCA is abundant in the proximal segment relative to the distal part, the RCA is deeply embedded in EAT from the ostium to the mid/distal segment (Figure). Thus the distribution of plaque rupture is consistent with the location of EAT-rich segments, suggesting that epicardial fat may promote atherosclerotic progression of coronary arteries via VV as shown in the current study.5
Images of a cadaver heart showing the abundant epicardial adipose tissue (EAT) of the proximal left anterior descending (LAD) and left circumflex (LCX) arteries (A-1,A-2), and less EAT in the lateral or apex of the left ventricle (LV). (B) The right coronary artery (RCA) is located in the atrioventricular groove of the right atrium (RA) and right ventricle (RV), where EAT is also abundant. LAA, left atrial appendage.
The role of chronic inflammation in EAT has been evaluated in a clinical study from the same group. Hirata et al7 collected EAT and subcutaneous adipose tissue (SCAT) from patients undergoing coronary artery bypass graft (CABG) and those with non-coronary arterial disease (non-CAD). They found the degree of inflammation was significantly higher in the EAT of the CABG patients compared with the non-CAD patients, but the degree of inflammation in SCAT was similar in both patient groups. They suggested an association between chronic inflammation in EAT and plaque progression in the human coronary artery. Ito et al demonstrate an association between adventitial VV and plaque progression. However, one of the limitations of the study was that they evaluated LADs from the cadavers of patients who had died from “non-CAD”. Further studies are needed to prove the association of VV with inflammation and more advanced atherosclerotic plaque progression. Kolodgie et al reported that the VV is more frequently seen at the site of plaque rupture followed by unstable plaque and least in stable lesions.8 Furthermore, the VV is not only the source of infiltrating inflammatory cells but also causes intraplaque hemorrhage due to the VV in advanced coronary plaque being leaky.
EAT volume can be quantified by several imaging modalities, such as coronary CT, echocardiography, and MRI, and the amount of EAT is associated with coronary events in the general population independent of traditional cardiovascular risk factors.9 However, detection of VV, with a diameter of 50–300 μm, remains difficult. Using intravascular ultrasound (IVUS), as in the current study, is theoretically able to visualize VV with its resolution (100 μm) and penetration depth (8–10 mm). Kume et al showed an IVUS image of VV that was confirmed by histology;10 however, the resolution of IVUS is not high enough to visualize VV in beating coronary arteries. Optical coherence tomography (OCT) has higher resolution (10 μm) than IVUS, and Vorpahl et al11 reported the possibility of visualizing VV that was less than 250 μm in diameter in ruptured plaque. However, OCT may have limitations to visualizing adventitial VV: limited penetration depth (a few millimeters) and attenuation of light by lipid-rich coronary plaques.12 Nishiyama et al previously demonstrated that OCT can visualize VV following stent implantation in pig coronary arteries, which was confirmed by histologic correlation, but detection of VV was limited to the stent edge segment in the real-world setting with human coronary arteries.13 These findings suggest that recognition of VV by OCT is highly dependent on lesion morphology and visualization of VV adjacent to lipid-rich plaque with a large necrotic core is most likely impossible because of attenuation. We have reported ring-enhancement of coronary plaques by MDCT as a risk factor of transient slow-flow during coronary intervention, which may indicate abundant VV is enhanced together with formation of vulnerable plaques.14 As is shown in the current study,5 visualization of VV could be the key to predicting future plaque progression, suggesting a need for the better imaging modalities in daily clinical practice.
