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Original Articles

Relationship of Microchannels and Plaque Erosion in Patients with ST-Segment Elevation Myocardial Infarction: An Optical Coherence Tomography Study

Jiang, Senqing; Guo, Junchen; Yin, Yanwei; Fang, Chao; Wang, Jifei; Wang, Yidan; Lei, Fangmeng; Sun, Sibo; Pei, Xueying; Jia, Ruyi; Zhang, Shaotao; Li, Lulu; Wang, Yini; Xing, Lei; Yu, Huai; Liu, Huimin; Xu, Maoen; Ren, Xuefeng; Ma, Lijia; Wei, Guo; Hou, Jingbo; Dai, Jiannan; Yu, Bo

Editor(s): Xu, Tianyu; Fu, Xiaoxia

Author Information
doi: 10.1097/CD9.0000000000000054
  • Open

Abstract

CLINICAL PERSPECTIVE

WHAT IS NEW?

  • The plaque with microchannels had higher low-density lipoprotein cholesterol level and higher incidence of multi-vessel disease than those without in patients with ST-segment elevated myocardial infarction caused by plaque erosion.
  • The microchannel group had more vulnerable plaque characteristics such as macrophages, cholesterol crystals, and spotty calcification and presented as more severe lumen stenosis than the no-microchannel group.

WHAT ARE THE CLINICAL IMPLICATIONS?

  • Even in patients with plaque erosion, the microchannels might play a key role in identifying lesions more prone to destabilization.
  • Microchannels may be a good therapeutic target for plaque stability.

Introduction

Acute coronary syndrome including ST-segment elevation myocardial infarction (STEMI) remains a significant global public health problem.[1] Plaque erosion is responsible for 22% to 44% of STEMI patients.[2] Pathology studies have shown that plaque erosion occurs over lesions that are rich in smooth muscle cells and proteoglycans, with superficial endothelial denudation.[3] Microchannels are associated with the progression of atherosclerotic vulnerable plaques.[4,5] However, in patients with plaque erosion, the knowledge of microchannels and culprit lesion vulnerability is still limited. Optical coherence tomography (OCT) is an intracoronary imaging modality with a high resolution,[6,7] having the potential to identify plaque erosion and microchannels.[8] The purpose of this study was to determine the characteristics of eroded plaques with and without micro-channels in patients with STEMI.

Materials and method

Study population

This is a retrospective observational cohort of STEMI patients admitted to the 2nd Affiliated Hospital of Harbin Medical University (Harbin, China) who underwent preintervention OCT imaging of culprit lesions during emergency percutaneous coronary intervention (PCI). The main exclusion criteria were cardiogenic shock, end-stage renal disease, serious liver dysfunction, allergy to contrast media, and contraindication to aspirin or ticagrelor. Patients with left main disease, chronic total occlusion, and extremely tortuous or heavily calcified vessels were not included because of the potential difficulty in performing OCT in such situations. Thus, from August 2014 to December 2017, 1660 STEMI patients who underwent OCT examinations before PCI in the 2nd Affiliated Hospital of Harbin Medical University were included. Of these patients, 218 were excluded because of the following reasons: pre-dilation before OCT examination (n= 31), poor OCT image quality or massive thrombosis (n = 129), and in-stent thrombosis or neoatherosclerosis (n = 58). In all, 1442 STEMI patients with suitable OCT images of culprit lesions were analyzed. Among them, 1094 patients were excluded because of the following reasons: (1) plaque rupture (n = 972); (2) calcified nodules (n = 23); (3) dissection, coronary spasm, or tight stenosis (n = 99). Finally, 348 patients who presented with plaque erosion were included in the present study. The study flowchart is shown in Figure 1.

F1
Figure 1:
Study flowchart of the study. OCT: Optical coherence tomography; STEMI: ST-segment elevated myocardial infarction.

The study was approved by the ethics committee of the 2nd Affiliated Hospital of Harbin Medical University (No. KY2017-249), and all enrolled patients provided written informed consent.

Coronary angiogram analysis

Quantitative coronary angiography (QCA) analysis was performed using the Cardiovascular Angiography Analysis System 5.10 (Pie Medical Imaging B.V., Maastricht, The Netherlands). QCA parameters including minimal lumen diameter (MLD), reference vessel diameter (RVD), diameter stenosis (DS), and lesion length were measured according to the established criteria.[9]

OCT image acquisition and analysis

OCT was performed using a C7-XR/ILUMIEN OCT system (Abbott Vascular, Santa Clara, California, USA). All measurements were performed according to previously established consensus and guidelines.[10,11] Plaque erosion included both definite (the presence of an attached thrombus overlying an intact and visualized plaque) and probable erosions, defined as luminal irregularity without thrombus or with thrombus but without a superficial lipid or calcified plaque in the proximity of the thrombus.[12] Quantitative analysis was performed at 1-mm intervals on cross-sectional OCT images. Fibrous cap thickness (FCT) and thin-cap fibroatheroma (TCFA) were measured according to the established criteria.[8] Microchannel was defined as a no-signal luminal structure with a diameter of 50 to 300 μm recognized on 3 consecutive cross-sectional OCT images. Macro-phages, cholesterol crystals, calcification, and spotty calcium deposition were recorded according to the established criteria.[8]

Statistical analysis

Data distribution was assessed according to the Kolmogorov-Smirnov test. For normally distributed data, continuous variables were presented as mean ± standard deviation (SD). For data that is not normally distributed, continuous variables were expressed as median (Q1, Q3). Independent sample t test and Mann-Whitney U test were conducted to detect between group differences. Categorical data were presented as counts (proportions) and were compared using the χ2 test or Fisher exact test. A multivariable logistic regression model (stepwise) was used to perform an assessment on the correlation between OCT, angiographical, clinical, and microchannel characteristics. Under the support of kappa statistics, the evaluation of inter- and intra-observer reliability was realized. Statistical significance was identified by a two-tailed P< 0.05. Statistical analyses were performed using SPSS version 20.0 (IBM Corporation, Armonk, New York, USA).

Results

Baseline clinical characteristics and laboratory data

A total of 348 STEMI patients with culprit plaque erosion were included in the present study. Among them, 116 (33.3%) patients with microchannel and 232 (66.7%) patients without microchannel were analyzed. The baseline characteristics of patients with and without microchannel are presented in Table 1. Low-density lipoprotein cholesterol (LDL-C) levels were higher in the microchannel group than the no-microchannel group (115.8 mg/ dL (93.6–137.3mg/dL) vs. 107.1 mg/dL (87.1–125.6 mg/dL), P = 0.034). There was no significant difference between the 2 groups in terms of demographic characteristics, risk factors, and history of myocardial infraction and PCI. The estimated intra-observer and inter-observer kappa coefficients for microchannel were 0.92 and 0.95, respectively.

Table 1 - Baseline clinical characteristics of 348 STEMI patients with culprit plaque erosion.
Microchannels

Variable All (n = 348) Yes (n = 116) No (n = 232) P
Age (years), mean ± SD 54.46 ± 11.01 54.32 ± 10.78 54.53 ± 11.15 0.866
Male, n (%) 276 (79.3) 95 (81.9) 181 (78.0) 0.400
Risk factors, n (%)
 Diabetes mellitus 52 (14.9) 21 (18.1) 31 (13.4) 0.266
 Hypertension 124 (35.6) 42 (36.2) 82 (35.3) 0.906
 Dyslipidemia 166 (47.7) 59 (50.9) 107 (46.1) 0.427
 CKD 20 (5.7) 10 (8.6) 10 (4.3) 0.141
Smoking status, n (%) 0.438
 Non-smoker 101 (29.0) 34 (29.3) 67 (28.9)
 Former smoker 27 (7.8) 6 (5.2) 21 (9.1)
 Current smoker 220 (63.2) 76 (65.5) 144 (62.1)
Laboratory data
 TC (mg/dL), median (Q1, Q3) 177.0 (151.2, 196.0) 179.8 (152.8, 200.8) 174.5 (150.3, 191.7) 0.080
 TG (mg/dL), median (Q1, Q3) 126.3 (86.8, 159.4) 119.5 (86.8, 166.6) 130.2 (87.0, 157.7) 0.765
 LDL-C (mg/dL), median (Q1, Q3) 111.2 (87.8, 129.3) 115.8 (93.6, 137.3) 107.1 (87.1, 125.6) 0.034
 HDL-C (mg/dL), median (Q1, Q3) 50.6 (42.8, 57.1) 47.8 (41.3, 56.8) 50.6 (43.7, 57.3) 0.114
 HbA1c (%), mean ± SD 6.09 ± 1.30 6.21 ± 1.54 6.02 ± 1.15 0.255
 eGFR (mL/(min·m2)), mean ± SD 92.10 ± 18.32 89.96 ± 20.16 93.18 ± 17.28 0.122
 LVEF (%), mean ± SD 57.32 ± 7.04 56.86 ± 7.33 57.56 ± 6.90 0.393
Previous history, n (%)
 Previous MI 7 (2.0) 3 (2.6) 4 (1.7) 0.690
 Previous PC 4 (1.1) 2 (1.7) 2 (0.9) 0.603
CKD: Chronic kidney disease; eGFR: Estimated glomerular filtration rate; HbA1c: Hemoglobin A1c; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; LVEF: Left ventricular ejection fraction; MI: Myocardial infarction; PCI: Percutaneous coronary intervention; STEMI: ST-segment elevated myocardial infarction; TC: Total cholesterol; TG: Triglyceride.

Angiographic findings

The angiographic findings are listed in Table 2. The frequency of multi-vessel disease was significantly higher in the microchannel group than the no-microchannel group (43.1% vs. 28.4%, P = 0.008). Distance to the ostium, severe calcification, DS, lesion length, RVD, and MLD were comparable between the 2 groups.

Table 2 - Angiographic findings of 348 STEMI patients with culprit plaque erosion.
Microchannels

Variable All (n = 348) Yes (n = 116) No (n = 232) P
Location, n (%) 0.147
 LAD 216 (62.2) 68 (58.6) 148 (64.1)
 LCX 28 (8.1) 14 (12.1) 14 (6.1)
 RCA 103 (29.7) 34 (29.3) 69 (29.9)
Type B2/C lesion, n (%) 268 (77.0) 94 (81.0) 174 (75.0) 0.226
Multi-vessel disease, n (%) 116 (33.3) 50 (43.1) 66 (28.4) 0.008
Bifurcation, n (%) 100 (28.8) 32 (27.6) 68 (29.4) 0.802
Severe calcification, n (%) 31 (8.9) 12 (10.3%) 19 (8.2) 0.551
QCA data, mean ± SD
 RLD (mm) 3.1 ± 0.5 3.1 ± 0.6 3.1 ± 0.5 0.746
 MLD (mm) 1.1 ± 0.5 1.1 ± 0.5 1.2 ± 0.5 0.219
 DS (%) 63.3 ± 14.2 65.0 ± 12.5 62.5 ± 15.0 0.101
 Lesion length (mm) 18.2 ± 9.0 18.1 ± 10.2 18.2 ± 8.4 0.944
DS: Diameter stenosis; LAD: Left anterior descending artery; LCX: Left circumflex artery; MLD: Minimal umen diameter; RCA: Right coronary artery; RLD: Reference umen diameter; STEMI: ST-segment elevated myocardial infarction.

OCT findings

The OCT findings are presented in Table 3. Representative OCT images are shown in Figure 2. The microchannel group had higher incidence of lipid plaque (59.5% vs. 45.3%, P= 0.012), calcification (41.4% vs. 24.6%, P = 0.002), spotty calcification (30.2% vs. 18.1%, P = 0.014), macrophages accumulation (72.4% vs. 45.7%, P < 0.001), and cholesterol crystals (32.8% vs. 14.2%, P < 0.001) than the no-microchannel group. The incidence of lipid-rich plaque tended to be higher in the microchannel group (55.2% vs. 44.4%, P = 0.058) than the no-microchannel group. Furthermore, minimal lumen area was smaller ((1.5 ± 0.7) mm2vs. (2.0 ± 0.7) mm2, P < 0.001) and lumen area stenosis was greater ((71.3% ± 13.4%) mm2vs. (65.3% ± 19.3%), P = 0.001) in the microchannel than the no-microchannel group.

Table 3 - OCT findings of 348 STEMI patients with culprit plaque erosion.
Microchannels

Variable All (n = 348) Yes (n = 116) No (n = 232) P
Distance to ostium (mm), median (Q1, Q3) 24.4 (15.8, 38.7) 25.5 (17.0, 36.5) 23.6 (15.7, 40.8) 0.970
Mean RLA (mm2), mean ± SD 7.8 ± 2.9 7.3 ± 2.6 8.0 ± 3.0 0.036
MLA (mm2), mean ± SD 2.5 ± 2.0 1.9 ± 0.9 2.8 ± 2.3 <0.001
AS (%), mean ± SD 67.31 ± 17.75 71.30 ± 13.38 65.30 ± 19.30 0.001
Plaque type, n (%) 0.012
 Fibrous plaque 174 (50.0) 127 (54.7) 47 (40.5)
 Lipid plaque 174 (50.0) 69 (59.5) 105 (45.3)
LRP, n (%) 167 (48.0) 64 (55.2) 103 (44.4) 0.058
TCFA, n (%) 47 (13.5) 12 (10.3) 35 (15.1) 0.248
Minimal FCT (μm), median (Q1, Q3) 91.9 (68.0, 115.0) 91.7 (68.3, 106.7) 95.0 (68.0, 125.0) 0.201
Lipid length (mm), mean ± SD 10.5 ± 5.3 10.3 ± 4.9 10.7 ± 5.5 0.669
Mean lipid arc (°), mean ± SD 220.2 ± 48.6 216.5 ± 51.0 222.6 ± 47.0 0.413
Maximal lipid arc (°), mean ± SD 301.4 ± 63.6 301.8 ± 66.3 301.1 ± 62.1 0.946
Calcification, n (%) 105 (30.2) 48 (41.4) 57 (24.6) 0.002
Spotty calcification, n (%) 77 (22.1) 35 (30.2) 42 (18.1) 0.014
Macrophage, n (%) 190 (54.6) 84 (72.4) 106 (45.7) <0.001
Cholesterol crystal, n (%) 71 (20.4) 38 (32.8) 33 (14.2) <0.001
AS: Area stenosis; FCT: Fibrous cap thickness; LRP: Lipid rich plaque; MLA: Minimal lumen area; RLA: Reference lumen area; STEMI: ST-segment elevated myocardial infarction; TCFA: Thin cap fibroatheroma.

F2
Figure 2:
Representative optical coherence tomography images of STEMI patients with culprit plaque erosion. (A) Plaque rupture (white arrow); (B) Plaque erosion (white arrow); (C) Fibrous plaque (white arrow); (D) Lipid plaque (red arc dotted line); (E) TCFA (red arrows); (F) Macrophage (white arrow); (G) Microchannel (white arrow); (H) Calcification (white arc dotted line); (I) Cholesterol crystals (white arrow). STEMI: ST-segment elevated myocardial infarction; TCFA: Thin-cap fibroatheroma.

Discussion

The present study provides novel observation regarding micro-channels in patients with plaque erosion. Our main findings were as follows: (1) The microchannel group had higher baseline LDL-C level and higher incidence of multi-vessel disease than the no-microchannel group. (2) The microchannel group had more vulnerable plaque characteristics such as macrophages, cholesterol crystals, and spotty calcification and presented as more severe lumen stenosis than the no-microchannel group.

The incidence of microchannels

OCT imaging is construed as a high-definition image formation method that can recognize microstructures within atheromatous plaques.[7,13,14] Vorpahl et al[15] reported that the small black holes discovered by OCT in atherosclerotic plaques that reflect microchannels were consistent with the histopathological proof of intraplaque microchannel generation in a necropsy example. Our team observed microchannels from plaque erosion at a rate of 33.3% by OCT method. This finding was consistent with that of Tenaglia et al,[16] who discovered new blood vessel formation from atherectomy samples at a rate of 36%.

Microchannel and plaque vulnerability

Depending on the stage of the disease, presence of microchannels within atherosclerotic plaques has a dual role.[17] In the early stage of disease progression, as the supply channel of myocardial tissue nutrition and oxygen, microchannels can protect myocar-dial tissue from ischemia; however, with disease progression, the balance between anti-angiogenic and pro-angiogenic factors is lost, and microchannels becomes increasingly immature and prone to rupture, promoting the transformation of stable plaque to unstable plaque.[18–20] With the progression of atherosclerosis, the lumen area will gradually decrease, which might explain why patients with microchannels have more severe luminal stenosis. Also, hemorrhages within atherosclerotic lesions would lead autologous erythrocytes to deliver into experimental plaques, which promote the formation of large necrotic core and macrophage infiltration. Moreover, intraplaque microchannel permits cholesterol-enriched erythrocyte cells into the plaque,[17,19–21] producing abundant cholesterol material for crystallization of cholesterol. This might explain why macro-phage and cholesterol crystals were more prevalent in the microchannel group than the no-microchannel group.

More recently, Moreno et al[21] discovered that there were more microchannels within TCFAs, indicating the vital role of intra-plaque microchannels as a biomarker for vulnerable plaques. Tian et al[22] used OCT technology to detect culprit and non-culprit lesions in patients with unstable angina pectoris (UAP) and stable angina pectoris, and then analyzed the influence of microchannel on plaque stability. The results showed that there were more vulnerable plaques in the culprit lesions of UAP patients than those without microchannel plaques: higher incidence of vulnerable plaques, thinner fiber cap, larger lipid angle, and longer length of lipid core. Intravascular ultrasound results also confirmed that there were microchannel plaques in the culprit lesions and the burden was greater than those without microchannels. The research results were consistent with those reported by Kitabata et al.[4] Because the sample size of this study was relatively small, and we only researched STEMI patients with plaque erosion, the results of the present study were not consistent with those of the previous study. Nonetheless, we still found that lipid plaques, macrophage infiltration, cholesterol crystal, and spotty calcification were more prevalent, which suggest that patients with intraplaque microchannels have vulnerable plaque structures.

In our study, patients with plaque erosion in the microchannel group had more vulnerable plaque characteristics such as macrophage, cholesterol crystals, and spotty calcification and showed more severe luminal stenosis than those in the no-microchannel group. The presence of microchannels in patients with plaque erosion may have more vulnerable plaque characteristics leading to plaque progression; therefore, more attention should be paid to disease progression in these patients, and the treatment plan should be adjusted in a timely manner to avoid recurrence of adverse cardiovascular events.

Clinical significance

The identification and stability of a vulnerable plaque are prime targets for accurate prediction and avoidance of coronary artery disease. Recently, experimental studies have shown that anti-atherosclerotic therapy can reduce plaque neovasculariza-tion[23,24] and that the inhibition of plaque neovascularization reduces plaque progression.[23] With the development of new technologies, we believe that OCT evaluation will allow us to better monitor the response to anti-atherosclerotic therapies, and that microchannels in plaques identified on OCT imaging can be as important a therapeutic target for plaque stabilization as FCT.

Limitations

The present study has some limitations. First, this is a retrospective observational study from a single center, and patients with highly unstable coronary plaques were not included in this study, which might have introduced a degree of selection bias. Second, in this in vivo study, OCT was used as the diagnostic criteria for plaque erosion, rather than other pathological diagnostic criteria. Current OCT cannot visualize individual endothelial, but the detachment of endothelial cells is one of the important pathological features for defining erosion. So, it is widely used and accepted that the OCT definition of plaque erosion requires the absence of fibrous cap rupture. The macrophage cannot be identified from the OCT images. It should preferably be identified by dedicated algorithm or software. However, the quantitative analysis of macrophages requires special algorithms or software, and its accuracy is still controversial. Our research is only a qualitative analysis of the presence of macrophages. Third, this study mainly aims at analyzing and comparing the clinical, angiographic, and OCT characteristics of plaque erosion in patients with or without microchannels. However, whether microchannel within the plaque erosion will have an impact on the prognosis of patients remains to be studied. Finally, the study population was relatively small. Further investigations in future large-scale cohort studies are needed.

Conclusion

In patients with STEMI caused by plaque erosion, approximately one-third of patients have typical microchannel characteristics, and patients with microchannels are associated with more severe luminal stenosis and more vulnerable plaque features than those without microchannels.

Acknowledgments

The authors sincerely thank all colleagues and patients who participated in this study.

Funding

This work was supported by the National Key R&D Program of China (grant No. 2016YFC1301100 to BY), National Natural Science Foundation of China (grant No. 81827806 to BY and No. 82072091 to JD), and Natural Science Foundation of Heilongjiang Province (grant No. YQ2020H017 to JD).

Author Contributions

Senqing Jiang, Junchen Guo, Yanwei Yin: substantial contribution to the conception and design of research, data acquisition, and manuscript drafting.

Chao Fang, Jifei Wang, Yidan Wang, Fangmeng Lei, Sibo Sun, Xueying Pei, Ruyi Jia, Shaotao Zhang, Yini Wang: substantial contribution to data acquisition.

Lulu Li: substantial contribution to statistical analysis.

Lei Xing, Huai Yu, Guo Wei, Huimin Liu, Maoen Xu, Xuefeng Ren, Lijia Ma: substantial contribution to patient enrollment and performance of cardiac intervention.

Jingbo Hou, Jiannan Dai, Bo Yu: substantial contribution to the design of research and critical manuscript revision.

Conflicts of Interest

None.

Editor Note: Bo Yu is an Editorial Board Member of Cardiology Discovery. The article was subject to the journal's standard procedures, with peer review handled independently of this editor and his research group.

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Keywords:

Optical coherence tomography; Microchannel; Plaque erosion

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