Author + information
- Sining Hu, MD‡,§,
- Taishi Yonetsu, MD§,
- Haibo Jia, MD, PhD‡,§,
- Antonios Karanasos, MD‖,
- Aaron D. Aguirre, MD, PhD¶,
- Jinwei Tian, MD, PhD‡,§,
- Farhad Abtahian, MD, PhD§,
- Rocco Vergallo, MD§,
- Tsunenari Soeda, MD, PhD§,
- Hang Lee, PhD#,
- Iris McNulty, RN§,
- Koji Kato, MD, PhD∗∗,
- Bo Yu, MD, PhD‡∗ (, )
- Kyoichi Mizuno, MD, PhD∗∗,
- Konstantinos Toutouzas, MD‖,
- Christodoulos Stefanadis, MD‖ and
- Ik-Kyung Jang, MD, PhD§,† ()
- ‡Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
- §Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- ‖First Department of Cardiology, Athens Medical School, Hippokration Hospital, Athens, Greece
- ¶Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- #Biostatistics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- ∗∗Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan
- ↵∗The Second Affiliated Hospital of Harbin Medical University, Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, 246 Xuefu Road, Nangang District, Harbin 150086, China
- ↵†Cardiology Division, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, GRB 800, Boston, Massachusetts 02114
To the Editor:
Previous studies have shown that plaque rupture and plaque erosion are the 2 most common underlying mechanisms for sudden cardiac death and acute coronary syndrome (1,2). In a rupture, the exposure of the necrotic core to the circulation is the primary thrombogenic substrate, whereas in erosion, proteoglycan and smooth muscle cells are believed to be the primary stimuli for thrombosis (1,3). Because it is known that the necrotic core is 6 times more thrombogenic than all other plaque components (4), it is possible that thrombus caused by erosion may respond better to fibrinolytic therapy compared with those caused by rupture.
In this study, we compared the residual thrombus burden, distribution, and characteristics of patients with ST-segment elevation myocardial infarction (STEMI) caused by erosion versus rupture after successful reperfusion with fibrinolysis using optical coherence tomography (OCT).
Twenty-nine patients with STEMI who were treated with tenecteplase were enrolled in this study. Between 24 and 48 h after successful fibrinolysis, patients underwent nonocclusive time-domain OCT imaging of culprit lesions before any intervention. All patients provided written informed consent before the start of the study. The study protocol was approved by the Institutional Ethics Committee of Athens Medical School.
OCT images were analyzed at 0.5-mm intervals for a 10-mm segment, including 5-mm distal and 5-mm proximal to the site of minimal lumen area (MLA). Thrombus was defined as a floating or protruding mass into the lumen with a dimension ≥250 μm and was categorized as either erythrocyte-rich (red) thrombus, defined by high backscattering and high attenuation, or platelet-rich (white) thrombus, defined by homogeneous backscattering with low attenuation. Residual thrombus burden was evaluated by calculating the thrombus score based on a semiquantitative assessment of thrombus by summing the number of involved quadrants containing thrombus on cross-sectional OCT images (5). Plaque rupture was identified by the presence of fibrous cap discontinuity with a clear cavity formed inside the plaque. Plaque erosion was defined as the presence of intracoronary thrombus attached to the luminal surface with no detectable signs of fibrous cap rupture (Fig. 1A) (2). The relationship between the location of rupture site and MLA site was also evaluated.
All statistical analyses were performed by an independent statistician. Categorical variables are presented as counts and proportions, and comparisons of thrombus incidence rates among locations were performed based on multiple segments per patient by using GEE. Continuous variables are presented as mean ± SD and were examined using the Student t test between the 2 groups. All statistical analyses were performed with IBM SPSS software version 19.0 (SPSS Inc., Chicago, Illinois).
Of the 29 patients, 6 were excluded due to poor image quality. The mean age was 60.5 ± 10.9 years in the rupture group and 58.0 ± 11.9 years in the erosion group (p = 0.65). The time delay from symptom onset to fibrinolysis (3.5 ± 1.2 h [rupture] vs. 3.3 ± 0.9 h [erosion]; p = 0.78) and from fibrinolysis to catheterization (31.2 ± 8 h [rupture] vs. 33.1 ± 7.6 h [erosion]; p = 0.60) was similar between the 2 groups.
Of 23 culprit lesions, 11 (47.8%) were diagnosed as plaque rupture and 8 (34.8%) as plaque erosion. Four cases (17.4%) did not meet the criteria for either category. Rupture sites were located proximal to the MLA in 72.7%, at the MLA site in 18.2%, and distal to the MLA in 9.1% of patients. Thrombus burden was significantly greater for rupture than for erosion (14.2 ± 9.4 vs. 6.5 ± 4.5; p = 0.049) (Fig. 1B).
In a rupture, white thrombus was primarily located at the MLA sites (22.5%) compared to proximal (1.6%, p = 0.007) and distal (5.5%, p = 0.002) segment whereas red thrombus did not show such a marked difference (17.3% [proximal], 25.5% [MLA], and 31.9% [distal], NS) (Fig. 1C). In erosion, only white thrombus was detected, which was primarily located at the MLA sites except in 1 patient with minimal red thrombus in the proximal segment (Fig. 1D).
Our study demonstrates that residual thrombus burden 1 day after fibrinolysis was greater in a rupture compared with erosion in patients with successful fibrinolysis for STEMI. In a rupture, the core of the thrombus primarily consisted of platelets, and red thrombus was evenly distributed over the entire culprit lesion length. In erosion, white thrombus was the predominant type at the culprit site, and red thrombus was sparse. These findings suggest that underlying plaque morphology in STEMI plays an important role in thrombosis and subsequent response to thrombolytic therapy.
Some limitations exist in our study. First, the findings of the present study were based on a small cohort of patients who had successful fibrinolysis. Second, OCT was performed 1 day after fibrinolysis. It is possible that thrombus might have been reduced or resolved with continuous antithrombotic therapy, and residual thrombus could have been organized. However, it is unlikely that plaque morphology would have changed significantly during that period. Third, it is possible that small ruptures shadowed by overlying red thrombus were not detected, and therefore the diagnosis of erosion might have been overestimated.
The authors thank James Chan and Russell Joye for their editorial assistance with the manuscript.
Please note: Dr. Jang has received research grants and consulting fees from LightLab Imaging/St. Jude Medical. Dr. Jia has received a grant from the National Natural Science Foundation of China (81200076). Dr. Tian has received a grant from the National Natural Science Foundation of China (81300201). Dr. Vergallo has received a grant from the Enrico ed Enrica Sovena Foundation, Italy. Dr. Yu received a grant from the National Natural Science Foundation of China (30871064/C140401). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Hu, Yonetsu, and Jia contributed equally to this study.
- 2014 American College of Cardiology Foundation
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