Author + information
- Published online February 4, 2019.
- Erika Yamamoto, MD, PhD,
- Vikas Thondapu, MD, PhD,
- Eric Poon, PhD,
- Tomoyo Sugiyama, MD, PhD,
- Francesco Fracassi, MD,
- Jouke Dijkstra, PhD,
- Hang Lee, PhD,
- Andrew Ooi, PhD,
- Peter Barlis, MD, PhD and
- Ik-Kyung Jang, MD, PhD∗ ()
- ↵∗Cardiology Division, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, GRB 800, Boston, Massachusetts 02114
Acute coronary thrombosis with plaque erosion is responsible for about one-third of patients with acute coronary syndromes. The relationship between endothelial shear stress (ESS) and plaque erosion has not been systematically studied in patients so far.
A total of 18 acute coronary syndrome patients with plaque erosion were selected. Patients with side branches (>2 mm) were excluded. After optical coherence tomography (OCT)-based arterial reconstruction, ESS, endothelial shear stress gradient (ESSG), and oscillatory shear index (OSI) were calculated in every 0.25-mm segment.
The main findings are as follow: 1) thrombus involved the throat and area of peak ESS/ESSG in 17 of 18 lesions; and 2) in 14 cases (77.8%), thrombus began close to the throat and extended distally to the area of high OSI (Figure 1A). Of these 14 cases, 8 had a steeper proximal, 6 had a steeper distal shoulder; 3) in the remaining 4 cases (22.2%), thrombus was located proximal to the throat. These cases demonstrated more than 1 peak ESS/ESSG and proximal flow recirculation was observed in 3 of 4 lesions. All 4 cases had a plaque with steeper distal shoulder with a trend toward more severe stenosis. (Figure 1B).
The proatherogenic effect of low ESS is well known. Chronic exposure to low ESS can result in endothelial inflammation, apoptosis, and denudation as well as thrombin activation and platelet adhesion. Moreover, acute flow perturbation can promote toll-like receptor 2–mediated endothelial cell activation, endothelial cell apoptosis, and subsequent formation of neutrophil extracellular traps. The activation of neutrophil elastase also alters functions of endothelial cells, resulting in endothelial death. Finally, neutrophil extracellular traps can cause thrombosis through protease, tissue factors, and pro-oxidant enzymes (1). Whereas high ESS is generally thought to be atheroprotective, some studies have shown supraphysiological ESS/ESSG might be related to endothelial cell injury, denudation, and erosion (2). However, in both postmortem and in vivo studies, it is difficult to evaluate the endothelium in situ. In autopsy specimens, the endothelium is often detached from the subendothelial tissue and/or missing due to autolysis. The endothelium may also “desquamate” due to manipulation, surgical or interventional retrieval of fresh tissue, and during processing for microscopic examination. Loss of endothelial cells under a thrombus may also be a result of thrombosis rather than the cause of thrombosis. In vivo, the endothelium is below the resolution of OCT and therefore cannot be directly studied with the current OCT systems. Studies have reported that a high shear rate activates both platelets and coagulation factors (3). We hypothesize that high ESS and ESSG at the minimal lumen area may activate both platelet and coagulation cascades, which may then extend to the distal segment, resulting in thrombus propagation along the direction of blood flow. OSI is a measure of the change in ESS vectors over the cardiac cycle. In effect, it is an index of blood flow recirculation. Red blood cells and platelets have been shown to deposit preferentially in areas of high OSI and blood recirculation (4).
This study has limitations. First, because the presence of side branches affects local ESS, patients with large side branches were excluded. Second, as thrombus obscures underlying lumen border on OCT images, there was some measure of estimation when segmenting contours for the arterial reconstructions. Third, the exact location of thrombus attachment to the underlying vessel wall could not be identified. Fourth, an OCT diagnosis of erosion is a diagnosis of exclusion.
In conclusion, in the majority of plaque erosion cases, thrombus localizes in the region between high ESS/ESSG at the throat and high OSI/low ESS at the distal shoulder. High shear stress may play a key role in initiating thrombotic processes, and both high OSI/low ESS and plaque geometry may determine the location and extension of thrombus (Figure 1C).
Please note: Dr. Jang has received grants from Abbott Vascular and Medicure; and consulting fees from Lycotec. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Yamamoto and Thondapu contributed equally to this work and are joint first authors.
- 2019 American College of Cardiology Foundation