2020 Volume 84 Issue 12 Pages 2235-2243
Background: The relationship between the characteristics of tissue protrusion detected by using optical coherence tomography (OCT) and the findings of coronary angioscopy (CAS) immediately after stent implantation were evaluated.
Methods and Results: A total of 186 patients (192 stents) underwent OCT before and after stenting and were observed by using CAS immediately after stenting and at the chronic phase. Patients were assigned to irregular protrusion, smooth protrusion, and disrupted fibrous tissue protrusion groups according to OCT findings. Serum high-sensitivity C-reactive protein (hs-CRP) levels were measured before and after stent implantation. The grade of yellow color (YC) and neointimal coverage (NC), and incidence of thrombus in the stented segment were evaluated by using CAS. After stent implantation, maximum YC grade (smooth, 0.64±0.80; disrupted fibrous tissue, 0.50±0.77; irregular, 1.50±1.09; P<0.0001), a prevalence of Max-YC grade of 2 or 3 (smooth, 17%; disrupted fibrous tissue, 17%; irregular, 50%; P<0.0001) and thrombus (smooth, 15%; disrupted fibrous tissue, 10%; irregular, 69%; P=0.0005), and elevated hs-CRP levels (smooth, 0.22±0.89; disrupted fibrous tissue, −0.05±0.29; irregular, 0.75±1.41; P=0.023) were significantly higher in irregular protrusion than in the other 2 groups. In the chronic phase, maximum- and minimum-NC grade and heterogeneity index, and thrombus did not differ significantly among the 3 groups.
Conclusions: Irregular protrusion was associated with atherosclerotic yellow plaque, incidence of thrombus, and vascular inflammation. The angioscopic findings in the chronic phase may endorse the clinical efficacy of second- and third-drug eluting stents, regardless of the tissue protrusion type.
Tissue protrusion is generally defined by using intravascular ultrasound (IVUS) as a tissue prolapse into the lumen through stent struts after stent implantation. Although previous studies have reported that tissue protrusion detected by using IVUS was attributable to early stent thrombosis, the clinical prognosis for tissue protrusion is controversial.1–3 The use of optical coherence tomography (OCT), which has a 10-fold higher resolution than IVUS, has enabled clinicians to evaluate tissue protrusion in more detail. A recent report documented that irregular protrusions identified by OCT were independent predictors of 1-year device-oriented clinical endpoints, in particular, target lesion revascularization (TLR).4 Other studies reported that the presence of irregular protrusions identified by OCT after second-generation drug eluting stent (DES) implantation was associated with subsequent neoatherosclerosis formation at 8 months.5 It is conceivable that the fibrous cap overlying the lipid plaque with a large necrotic core would be easily disrupted and can protrude between stent struts, resulting in an irregular protrusion.6 However, irregular protrusion has not yet been validated by macroscopic pathology and histology.
Coronary angioscopy (CAS) has allowed for the direct visualization of the intracoronary structure and provided substantial information pertaining to macroscopic pathology in living patients.7 Therefore, the aim of the present study was to assess the relationship between the characteristics of tissue protrusion detected by using OCT and the findings of CAS immediately after stent implantation and in the chronic phase.
This study was retrospectively conducted in our institution from January 2012 to February 2018. We performed OCT before and immediately after stent implantation in coronary artery disease (CAD) patients who underwent percutaneous coronary intervention (PCI). CAS was also performed immediately after stent implantation and at 1 year after PCI (chronic phase). A total of 186 patients with 192 lesions were enrolled (Figure 1). Laboratory data were obtained on admission and at 1 year after PCI. Stent implantation was performed by using current conventional techniques. There were 99 lesions with second DES implantation (39 lesions with an everolimus-eluting stent, 55 with a zotarolimus-eluting stent, and 5 with a biolimus-eluting stent) and 86 lesions with third DES implantation (44 with bioabsorbable polymer everolimus-eluting stent and 42 with bioabsorbable polymer sirolimus-eluting stent). The interventional strategy was at the discretion of the operators. All patients received dual antiplatelet therapy with aspirin (100 mg/day) and clopidogrel (75 mg/day) or prasugrel (3.75 mg/day) before PCI, and heparin administration with the goal of an activated coagulation time >300 s. Serial measurements of high-sensitive CRP (hs-CRP) were performed at both baseline and 24 h after PCI, with the aim of assessing PCI-related vascular inflammation. The present study was performed in agreement with the Declaration of Helsinki for investigations in human patients, and all patients provided written informed consent for the PCI procedures. The institutional review board of the University of Tsukuba approved the data collection (reference number. R01-075).
Patient flow chart. CAG, coronary angiography; OCT, optical coherence tomography; PCI, percutaneous coronary intervention.
Coronary angiograms were obtained at baseline, after stent implantation and at 1-year follow up. Quantitative coronary angiography (QCA) analysis for lesion length, lesion minimal luminal diameter (MLD) and reference vessel diameter was performed by using an off-line QCA system (CASS 5.9; Pie Medical Imaging, Maastricht, the Netherlands). We calculated late lumen loss as in-stent MLD after intervention minus in-stent MLD at follow up.
OCT Image Acquisition and AnalysisA frequency-domain OCT system (FD-OCT) (C7-XRTM OCT Intravascular Imaging System and ILUMIENTM OCT Intravascular Imaging Systems, St. Jude Medical, St. Paul, MN, USA) and the DragonflyTM catheter (St. Jude Medical Inc.) were used. OCT analysis was performed before and immediately after stent implantation. The imaging catheter was advanced to the distal end of the culprit lesion, and the stent over a conventional guidewire and was automatically pulled back at 20 mm/s. We continuously filled the coronary artery with a mixture of contrast media and low molecular weight dextran during the pull back. In the current study, qualitative and quantitative evaluation was performed for all cross-section images. Qualitative and quantitative analyses of plaque morphologies were performed using the criteria for plaque characterization, which was validated in a previous study.5,8,9 Lipid was defined as a signal-poor region with a poorly delineated or diffuse border. Before stenting, the degree of lipid arc and the fibrous cap thickness at the thinnest part were measured in lipidic plaques. Plaque calcification was defined as a single poor region with a sharply delineated border. Tissue protrusion was defined when material was detected by OCT into the stent lumen immediately after stenting. When the stent struts were embedded in the intima, we included tissue protrusion with a maximum height ≥100 mm for analysis. According to criteria set in a previous study,3 we classified the tissue protrusion into three groups: smooth protrusion, disrupted fibrous tissue, or irregular protrusion (Figure 2). Smooth protrusion was defined as the bowing of a plaque into the lumen between the stent struts without intimal disruption. Disrupted fibrous tissue was defined as the disruption of the underlying fibrous tissue protrusion into the lumen between the stent struts. Irregular protrusion was defined as protrusion of the material with an irregular surface into the lumen between the stent struts. Because we often recognize several different types of protrusion within the same stented segment, we evaluated the most protruding sites at the narrowest culprit sites as the dominant tissue protrusions. Thrombus was defined as a mass with a diameter ≥250 μm attached to the luminal surface, stent strut, or floating within the lumen. OCT is capable of discriminating between 2 types of thrombus: red thrombus, which has a high attenuation, and white thrombus, which is homogeneous and has low attenuation. When the material on the stent struts could not be distinguished from thrombus and irregular protrusion, we categorized it as an irregular protrusion.
Optical coherence tomography (OCT) and coronary angioscopy images of tissue protrusions. Tissue protrusion (yellow arrows) was classified into three groups according to the OCT: smooth protrusion (A), disrupted fibrous tissue (B), and irregular protrusion (C). Coronary angioscopy showed white tissue (D), disrupted white tissue (E), and glistering yellow plaques with red thrombus (red arrow) (F) prolapsed within the stent struts.
The coronary angioscopic examination was performed by using a non-obstructive coronary angioscope FT-203F (FiberTech Co. Ltd., TokyoRX-3310A & MV-5010A; Machida, Tokyo, Japan) and the VISIBLE (FiberTech Co. Ltd). We observed stented lesions with the angioscopy while blood was removed from the field of view by the injection of low molecular weight dextran, as previously reported.10 Neointimal coverage (NC) grade was classified into 4 grades, as previously described.10,11 In brief, grade 0=stent struts completely exposed (similarly to immediately after implantation); grade 1=stent struts visible with dull light reflection; grade 2=no light reflection from the stent struts with slightly visible struts; grade 3=stent struts completely covered and not visible through the neointima. We assessed the minimum (Min-) and maximum (Max-) NC grade, and the heterogeneity index was calculated as Max-NC grade minus Min-NC grade. Yellow color (YC) under the stent was categorized into 4 grades (0, white; 1, slight yellow; 2, yellow; and 3, intensive yellow), as previously described.10,11 Maximum (Max-) YC grade and presence or absence of thrombus was determined for each stented lesion based on the criteria adopted by the European Working Group on Coronary Angioscopy.12 The difference between thrombus and irregular protrusion was evaluated by referring to the difference in color tone and surrounding lesion characteristics. The red and white thrombus was observed by the red and white color by CAS, respectively. The OCT and angioscopic findings were interpreted by 2 experienced observers blinded to the angiographic and clinical data. Intraclass correlation coefficients were calculated to assess intra- and interobserver agreement for tissue protrusion and color grade. The intra- and interobserver correlation coefficients of tissue protrusion and color grade were 0.91 and 0.85, 0.92 and 0.90, respectively. When there was discordance between the readings, a third reading was obtained for consensus.
Statistical AnalysisCategorical variables were presented as frequencies and percentages and were compared using the chi-squared test or Fisher’s exact test. Continuous variables were shown as mean±standard deviation (SD) or as median and interquartile range for non-normally distributed data. Comparisons among 3 groups with non-parametric population were performed using the Kruskal-Wallis test and Steel’s multiple comparison test. Comparing continuous variables among the 3 groups, analysis of variance (ANOVA) was used and the Tukey-Krammer test was performed for post-hoc analysis when there was a significant difference found by the ANOVA. For between-group comparisons, chi-squared or Fisher’s exact test for categorical outcomes was used to identify overall differences, and then post-hoc tests using Bonferroni’s correction were performed if the overall test was significant. A P value <0.05 was considered to be statistically significant. All analyses were performed using the EZR software (version 2.3-0; Saitama Medical Center, Jichi Medical University, Saitama, Japan).
We analyzed a total of 192 consecutive lesions after stent implantation by both OCT and CAS in 186 patients who underwent PCI (Figure 1). Tissue protrusion was detected by OCT in 96.4% (185/192 lesions) of lesions. Tissue protrusions were divided into 3 groups according to morphological characteristics. The smooth protrusion group included 87 patients with 92 lesions (50%), the disrupted fibrous tissue group included 33 patients with 34 lesions (18%), and the irregular protrusion group had 59 patients with 59 lesions (32%). Baseline patient characteristics are shown in Table 1. Patients with smooth protrusions had a lower prevalence of chronic kidney disease compared to patients in the other groups. Patients with irregular protrusion had a higher prevalence of acute coronary syndrome (ACS). Serum HDL-cholesterol level was lower in the irregular protrusion group than in the other 2 groups. There were no significant differences among 3 groups in terms of coronary risk factors such as diabetes mellitus, hypertension, and hyperlipidemia. At 1 year after PCI, there were no significant differences in each metabolic parameter among the 3 groups.
| Characteristic | Smooth protrusion (n=87) |
Disrupted fibrous tissue (n=33) |
Irregular protrusion (n=59) |
P value |
|---|---|---|---|---|
| Age (years) | 68.5±9.1 | 69.0±8.0 | 67.3±9.7 | 0.615 |
| Male sex (%) | 69 (79) | 21 (63) | 47 (80) | 0.273 |
| Hypertension (%) | 56 (64) | 28 (85) | 42 (71) | 0.089 |
| Dyslipidemia (%) | 68 (78) | 23 (70) | 41 (69) | 0.426 |
| Diabetes (%) | 31 (36) | 11 (33) | 23 (39) | 0.850 |
| CKD (%) | 22 (25) | 13 (40) | 31 (53) | 0.005 |
| Smoking (%) | 34 (40) | 12 (36) | 24 (41) | 0.889 |
| ACS (%) | 10 (12) | 2 (6) | 67 (12) | 0.455 |
| Aspirin (%) | 85 (98) | 33 (100) | 58 (98) | 0.683 |
| DAPT (%) | 80 (92) | 31 (94) | 56 (95) | 0.771 |
| ACE-I/ARB (%) | 39 (49) | 14 (42) | 31 (53) | 0.557 |
| β-blocker (%) | 51 (59) | 18 (55) | 39 (66) | 0.499 |
| Statin (%) | 66 (76) | 26 (79) | 50 (86) | 0.290 |
| Laboratory data, Baseline | ||||
| Cre (mg/dL) | 0.92±0.39 | 0.96±0.50 | 1.06±0.55 | 0.233 |
| HbA1c (%) | 6.3±1.1 | 6.1±0.9 | 6.3±1.2 | 0.731 |
| LDL cholesterol (mg/dL) | 97.7±30.2 | 99.7±37.4 | 97.6±32.7 | 0.156 |
| HDL cholesterol (mg/dL) | 47.4±13.2 | 47.5±9.0 | 42.3±11.1 | 0.034 |
| Triglyceride (mg/dL) | 154±85.9 | 119±38.8 | 155±88.8 | 0.067 |
| C-reactive protein (mg/L) | 0.07 (0.16–0.60) | 0.08 (0.06–0.62) | 0.07 (0.16–0.56) | 0.794 |
| At 1 year after PCI | ||||
| Cre (mg/dL) | 0.93±0.34 | 1.01±0.68 | 1.04±0.60 | 0.524 |
| HbA1c (%) | 6.4±0.9 | 6.0±0.6 | 6.5±1.1 | 0.178 |
| LDL cholesterol (mg/dL) | 83.7±21.3 | 85.1±23.6 | 75.9±20.2 | 0.141 |
| HDL cholesterol (mg/dL) | 47.3±12.3 | 45.9±8.7 | 46.0±10.8 | 0.806 |
| Triglyceride (mg/dL) | 154.8±68.7 | 138.4±60.8 | 150.8±69.9 | 0.620 |
Values are presented as mean±SD or median and interquartile range. ACE-I, angiotensin-converting enzyme inhibitor; ACS, acute coronary syndrome; ARB, angiotensin II receptor blocker; Cre, creatinine; CKD, chronic kidney disease; DAPT, dual antiplatelet therapy; LDL, low-density lipoprotein; HDL, high-density lipoprotein; PCI, percutaneous coronary intervention.
Baseline lesion and procedural characteristics are shown in Table 2. Stent types, stent length and stent diameter had no significant relationship with the morphology of tissue protrusion. Lipid arc and length were significantly greater in the irregular protrusion group than in the other groups (P<0.001), whereas fibrous cap thickness was less in the irregular protrusion group than in the other groups (P<0.001).
| Characteristic | Smooth protrusion (n=92) |
Disrupted fibrous tissue (n=34) |
Irregular protrusion (n=59) |
P value |
|---|---|---|---|---|
| Stent type | 0.491 | |||
| Second-generation DES (%) | 49 (53) | 20 (59) | 30 (51) | |
| Third-generation DES (%) | 43 (47) | 14 (41) | 29 (49) | |
| Target vessel | ||||
| LMT (%) | 1 (1) | 1 (3) | 0 (0) | 0.082 |
| LAD (%) | 49 (53) | 17 (50) | 22 (37) | 0.188 |
| RCA (%) | 25 (28) | 11 (32) | 28 (47) | 0.051 |
| LCX (%) | 18 (20) | 5 (14) | 9 (15) | 0.718 |
| Stent length (mm) | 20.6±7.2 | 20.1±7.7 | 22.7±8.8 | 0.170 |
| Stent diameter (mm) | 2.8±0.4 | 3.0±0.5 | 3.0±0.5 | 0.499 |
| Late loss (mm) | 0.081 (0.09–0.42) | 0.085 (0.03–0.38) | 0.098 (0.09–0.30) | 0.444 |
| OCT findings before intervention | ||||
| Lipid arc (degree) | 134.3 (116.0–152.6) | 118.9 (85.7–152.1) | 224.6 (201.6–247.6) | <0.001 |
| Fibrous cap thickness (μm) | 336.0 (294.6–977.4) | 310.8 (239.1–382.5) | 160.6 (110.8–210.3) | <0.001 |
| Lipid length (mm) | 6.7 (5.53–7.77) | 5.0 (3.00–7.06) | 11.6 (10.2–13.1) | <0.001 |
| Plaque calcification (%) | 67 | 76 | 58 | 0.258 |
| Reference lumen area (mm2) | 5.94±2.92 | 6.12±3.03 | 6.39±3.14 | 0.694 |
| Lesion length (mm) | 19.7±8.0 | 17.4±10.3 | 21.6±8.7 | 0.129 |
Values are presented as mean±SD or median and interquartile range, unless otherwise stated. DES, drug-eluting stent; LAD, left anterior descending; LCX, left circumflex; LMT, left main trunk; OCT, optical coherence tomography; RCA, right coronary artery.
Representative OCT and CAS images of tissue protrusion can be seen in Figure 2 and Supplementary Movies 1–3. The findings detected by CAS regarding YC grade are shown in Figure 3. Max-YC grade (smooth, 0.64±0.80; disrupted fibrous tissue, 0.50±0.77; irregular, 1.50±1.09; P<0.0001) and prevalence of Max-YC grades 2 or 3 (smooth, 17%; disrupted fibrous tissue, 17%; irregular, 50%; P<0.0001) were significantly higher in the irregular protrusion group than in the other protrusion groups (Figure 3). The incidence of thrombus was most frequent in the irregular protrusion group (smooth, 15%; disrupted fibrous tissue, 10%; irregular, 69%; P=0.0005, Figure 4A). The increase in hs-CRP levels after stent implantation was significantly more frequent in the irregular protrusion than in the other protrusion groups (smooth, 0.22±0.89; disrupted fibrous tissue, −0.05±0.29; irregular, 0.75±1.41; P=0.023, Figure 4B).
Max-yellow color grade of coronary angioscopy after stent implantation. Max-yellow color grade (A) and the prevalence of yellow color grade 2 or 3 (B) were significantly higher in irregular protrusions than in other protrusions. Max-YC grade: smooth, 0.64±0.08; disrupted fibrous tissue, 0.50±0.77; irregular, 1.50±1.09; P<0.0001. Prevalence of Max-YC grades 2 or 3: smooth, 17%; disrupted fibrous tissue, 17%; irregular, 50%; P<0.0001.
Incidence of thrombus after stent implantation and serial change of high sensitivity C-reactive protein (hs-CRP) from baseline to 24 h after stent implantation. (A) The incidence of thrombus was higher in irregular protrusions than in other protrusions. (B) Serial increase of hs-CRP from baseline to 24 h after stent implantation was greater in the irregular protrusions than in the other protrusions (smooth, 0.22±0.89; disrupted fibrous tissue, −0.05±0.29; irregular, 0.75±1.41; P=0.023).
In the chronic phase, Max-NC (smooth, 1.97±0.95; disrupted fibrous tissue, 1.88±0.83; irregular, 2.00±0.92; P=0.952) and Min-NC grades (smooth, 1.44±0.85; disrupted fibrous tissue, 1.13±0.35; irregular, 1.20±0.67; P=0.426) and heterogeneity indexes (smooth, 0.53±0.64; disrupted fibrous tissue, 0.75±0.70; irregular, 0.80±0.77; P=0.398) were not found to be significantly different among the 3 groups. There were also no significant differences in the prevalence of Max-NC (smooth, 64%; disrupted fibrous tissue, 62%; irregular, 60%; P=0.871) and Min-NC 2 or 3 grades (smooth, 41%; disrupted fibrous tissue, 13%; irregular, 20%; P=0.424) among the 3 groups (Figure 5). Furthermore, Max-YC grade (smooth, 0.46±0.68; disrupted fibrous tissue, 1.00±0.75; irregular, 0.73±0.79; P=0.118) and prevalence of Max-YC grades 2 or 3 (smooth, 10%; disrupted fibrous tissue, 25%; irregular, 20%; P=0.305) were not significantly different among the 3 groups (Figure 6) and there were no differences in the incidence of thrombus (smooth, 23%; disrupted fibrous tissue 25%; irregular, 27%; P=0.961). In contrast, there were also no significant differences in the late lumen loss among the 3 groups (smooth protrusion, 0.081 [0.09–0.42] mm; disrupted fibrous tissue protrusion, 0.085 [0.03–0.38] mm; irregular protrusion, 0.098 [0.09–0.30] mm, P=0.444). One patient died of myocardial infarction (MI) due to late stent thrombosis in the irregular protrusion group, whereas cardiac death, MI, and stent thrombosis did not occur in the other groups. The TLR tended to be more frequent in the irregular protrusion group (smooth, 4.6%; disrupted fibrous tissue, 3.0%; irregular, 8.5%; P=0.136) during the follow-up period (median, 18.1 [21.9–29.0] months).
Neointimal cover (NC) grade of coronary angioscopy, 1 year after stent implantation. There were no significant differences in maximum (Max)-NC grade (A), minimum (Min)-NC grade (B) and heterogeneity index (C) between the groups. There was no significant difference in the prevalence of Max-NC grade (D) and the Min-NC grade (E) between the groups. Max-NC: smooth, 1.97±0.95; disrupted fibrous tissue, 1.88±0.83; irregular, 2.00±0.92; P=0.952. Min-NC grades: smooth, 1.44±0.85; disrupted fibrous tissue, 1.13±0.35; irregular, 1.20±0.67; P=0.426. Heterogeneity indexes: smooth, 0.53±0.64; disrupted fibrous tissue, 0.75±0.70; irregular, 0.80±0.77; P=0.398.
Max-yellow color (YC) grade of coronary angioscopy, 1 year after stent implantation. There were no significant differences in max-yellow color grade (A) and the prevalence of yellow color grade 2 or 3 (B) between the groups. Max-YC grade: smooth, 0.46±0.68; disrupted fibrous tissue, 1.00±0.75; irregular, 0.73±0.79; P=0.118. Prevalence of Max-YC grades 2 or 3: smooth, 10%; disrupted fibrous tissue, 25%; irregular, 20%; P=0.305.
The major findings of this study were that irregular protrusions detected by using OCT were associated with high-grade yellow plaque observed by using CAS, compared to smooth and disrupted fibrous tissue protrusion, and the increase in hs-CRP levels after stent implantation and the incidence of thrombus detected by CAS were significantly more frequent in the irregular protrusion than other protrusion groups. In the chronic phase, Max- and Min-NC grade and heterogeneity index, YC grade, and thrombus were not significantly different among the groups. Finally, the TLR tended to be more frequent in the irregular protrusion group, although not significant. To our knowledge, this is the first report to analyze the relationship between the characteristics of tissue protrusion and findings of CAS. Furthermore, the incidence of irregular protrusions was associated with vascular inflammation after stent implantation. However, the angioscopic findings in the chronic phase may endorse the clinical efficacy and safety profile of second- and third-DES implantations, regardless of the tissue protrusion type.
Relationship Between Tissue Protrusion Morphology and CAS Findings After Stent ImplantationThe use of OCT enables physicians to provide high-resolution images of the lesion, compared to images obtained by using IVUS.13 Therefore, OCT can feasibly identify tissue protrusion more accurately than IVUS.14 Previous OCT studies have reported that tissue protrusion was observed in over 90% of the lesion after stenting.5,8,15,16 Recently, Soeda et al categorized OCT-detected stent tissue protrusion into 3 groups: smooth protrusion, disrupted fibrous tissue protrusion, and irregular protrusion.4 Bryniarski et al reported that a greater plaque burden, larger lipid content and a higher prevalence of thrombus were predictors of irregular protrusions.6 In the present study, we observed tissue protrusion directly by using both OCT and CAS. We classified tissue protrusion into 3 groups according to previous reports and performed a more detailed angioscopic analysis. We demonstrated that irregular protrusions were associated with a higher grade of yellow plaque and more frequent incidences of thrombus compared to the other protrusion groups. Irregular protrusion by OCT was considered when lipid core prolapse, and red, white or mixed thrombus were observed. It is challenging to differentiate between prolapse, thrombus, intimal, and intra-stent dissection and neointima by using OCT.9 Previous reports have also stated that materials between stent struts were classified as irregular protrusions when they could not be distinguished as thrombus or irregular protrusions.4–6 We revealed that a part of the irregular protrusion was a lipid core prolapse and the other part may be a thrombus. A report showed that tissue protrusion detected by using OCT after stent implantation was associated with high-grade yellow plaque with thrombi detected by using CAS.17 Furthermore, we demonstrated an increase in hs-CRP levels after stent implantation was more frequent in the irregular protrusion group than in the other protrusion groups. Prior pathological reports showed that arterial medial disruption and lipid core penetration by the stent struts were associated with increased arterial inflammation and increased neointimal growth.18–20
Relationship Between Tissue Protrusion Morphology and CAS Findings in the Chronic PhaseSimilar to the previous IVUS studies,1,2 several OCT studies have revealed that tissue protrusion has no relevance to clinical events.8,15,16 However, Soeda et al reported that irregular protrusion is an independent predictor of 1-year device-oriented clinical endpoints.4 Considering that the number of patients included in the study was too low to correlate OCT findings with clinical events, the clinical significance of intraluminal protrusion based on OCT remains unclear. In the present study, 1 patient died of MI due to late stent thrombosis, and TLR tended to be more frequent in the irregular protrusion group, whereas cardiac death, MI, and stent thrombosis did not occur in the other groups. In the chronic phase, Max- and Min-NC grades were not found to be significantly different among the 3 groups, and it was not associated with 1-year device-oriented clinical endpoints. Although the cause of the discrepancy is not clear at this time, in the study, higher use of second and third generation DESs and low prevalence of ACS may have had some contribution. The second- and third-generation DESs were developed to overcome the disadvantages of the first DES, such as over-suppression of neointimal proliferation and hypersensitivity to polymers, which are responsible for late stent failure.21 In clinical implication, we could investigate the characteristics of 3 types of protrusion in detail by using both OCT and angioscopy. In the present study, we demonstrated that the second- and third-DES implantation had adequate and homogeneous NC with white neointima and less occurrence of thrombus. These angioscopic findings endorse the clinical efficacy and safety profile of second- and third-DES implantations, and may explain the favorable clinical outcomes of treated patients, regardless of the tissue protrusion type.
Study LimitationsThis was a single center, retrospective study with a small sample size. It is possible that the incidence of thrombus and YC grade of the plaque at the stented lesions could have been underestimated because observation by using CAS was assessed for the part of the vessel wall within the field of vision where blood was cleared by dextran injection. In this study, we evaluated the sites with dominant tissue protrusion. The site observed by using CAS had both tissue protrusion and no tissue protusion. Both of these are completely different in nature, and their mixture greatly influences the interpretation of the results. Although there were a small number of clinical events that occurred in the current study, more detail and larger scale observation for irregular protrusions observed by using CAS will adjunctively assist in enhancing the validity of the results from this study.
Irregular protrusions detected by using OCT were associated with atherosclerotic yellow plaque, the incidence of thrombus as detected by using CAS, and vascular inflammation after stent implantation. The angioscopic findings in the chronic phase may endorse the clinical efficacy and safety profile of second- and third-DES implantations, regardless of tissue protrusion types.
The authors would like to thank Editage (http://www.editage.jp) for help with English-language editing.
The authors have no conflicts of interest to disclose.
The ethics committee of the University of Tsukuba approved this study (reference number [R01-075]).
Supplementary Movie 1. Smooth protrusion. Coronary angioscopy showing white tissue prolapsed within the stent struts.
Supplementary Movie 2. Disrupted fibrous tissue protrusion. Coronary angioscopy showing white disrupted fibrous tissue prolapsed within the stent struts.
Supplementary Movie 3. Irregular protrusion. Coronary angioscopy showing glistering yellow plaques with red thrombus prolapsed within the stent struts.
Please find supplementary file(s);
http://dx.doi.org/10.1253/circj.CJ-20-0306
