Morphological Characteristics of In-stent Restenosis with Different Degrees of Area Stenosis: An Optical Coherence Tomography Study

doi:10.21203/rs.3.rs-3087848/v1

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Research Article

Morphological Characteristics of In-stent Restenosis with Different Degrees of Area Stenosis: An Optical Coherence Tomography Study

https://doi.org/10.21203/rs.3.rs-3087848/v1

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Journal Publication

published 28 Feb, 2024

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Purpose

The morphological characteristics of in-stent restenosis (ISR) in relation to varying degrees of area stenosis have not been comprehensively examined. This study aimed to explore the tissue characteristics of patients experiencing ISR with different degrees of area stenosis through the utilization of optical coherence tomography (OCT).

Methods

In total, 230 patients with ISR who underwent OCT were divided into the following three groups: area stenosis (AS) < 70% (n = 26); 70%-80% (n = 119) and AS ≥ 80% (n = 85).

Results

Among the 230 patients, the clinical presentation as stable angina was 61.5% in AS < 70%, followed by 47.2% in 70% < AS ≤ 80%, and 31.8% in AS ≥ 80% (P = 0.010). The OCT findings showed that heterogeneous neointima, ISNA, LRP, neointima rupture, TCFA-like pattern, macrophage infiltration, red and white thrombus was more common with AS increased. Ordinal logistic regression analysis showed that higher AS was associated with previous dyslipidaemia (odds ratio [OR], 6.706, 95% confidence interval ([CI], 1.764–25.483; P = 0.005) and neointima rupture (odds ratio [OR], 4.472, 95% confidence interval ([CI], 1.228–16.281; P = 0.023).

Conclusions

Patients with higher degrees of area stenosis in the context of ISR exhibited a greater number of discernible morphological characteristics as identified through OCT analysis. Furthermore, previous dyslipidemia and neointima rupture was highly associated with and the progression of ISR lesions.

In-stent restenosis

Optical coherence tomography

Area stenosis

With the notable advancements in drug-eluting stents (DES) and their associated technologies, percutaneous coronary interventions (PCI) have experienced significant enhancements in terms of both efficacy and safety. However, despite the considerable progress made in stent technologies, the incidence of in-stent restenosis (ISR) remains substantial, necessitating target lesion with revascularization in approximately 1%-2% of ISR patients [1]. In the United States, PCI for ISR has accounted for 10% of all PCIs conducted in recent decades and has been link to a heightened risk of major adverse cardiac events when compared to PCI for de novo lesions [2, 3].

Presently, the prevailing definition of in-stent restenosis (ISR) entails a minimum narrowing of 50% of the vessel diameter [4]. Optical coherence tomography (OCT), owing to its superior tissue resolution, offers a fresh perspective for ISR research. Previous investigations have explored the association between OCT-identified tissue characteristics and various stent types [5–7]. However, there remains a lack of systematic research on the morphological features of ISR, specifically those pertaining to different areas of stenosis. Thus, the primary objective of this study was to investigate the tissue characteristics in patients with ISR across varying degrees of area stenosis (AS) using OCT.

Herein, we conducted a retrospective analysis of OCT images obtained from 230 patients with in-stent restenosis, encompassing diverse degrees of AS. Our findings revealed a progressive enhancement in the discernible morphological characteristics as the degree of AS increased. Furthermore, subsequent analysis identified previous dyslipidemia and neointima rupture as independent risk factors for a higher degree of AS. To the best of our knowledge, this study represents the first attempt to examine the relationship between OCT-identified morphological characteristics and different degrees of AS in patients with ISR, thus introducing a novel avenue for ISR investigation.

Study population

A retrospective analysis was conducted on a cohort of 252 consecutive patients with in-stent restenosis (ISR) who underwent optical coherence tomography (OCT) at the Affiliated Hospital of Zunyi Medical University between October 2018 and October 2022. ISR was defined as a diameter stenosis > 50% within the stent or in the 5-mm proximal or distal segments adjacent to the stent as determined by angiography. The exclusion criteria were applied, including: poor OCT image quality (n = 5), balloon pre-dilatation before OCT examination (n = 8) and absence of patients demographic data (n = 9). Ultimately, a total of 230 patients were included in the analysis. Based on OCT measurements, the patients were categorized into three groups according to AS measured by OCT: AS < 70%, 70% ≤ AS < 80% and AS ≥ 80%. The present study received approval from the Institutional Ethics Committee of the Affiliated Hospital of Zunyi Medical University.

Angiographic procedure

Coronary angiography (CAG) was performed using either the transradial or transfemoral approach, employing a 6F or 7F sheath. The culprit vessel was determined based on the coronary angiography results, supplemented by findings from electrocardiogram or echocardiogramas indicating possible myocardial ischemia. Coronary angiography (QCA) analysis was conducted using the software (Artis VC21C, Siemens AG, Berlin, and Munich) by an skilled physicians (L.Z.J) who remained blinded to the clinical characteristics of the patients. Essential measurements such as minimum lumen diameter, reference lumen diameter, and percentage of diameter stenosis were obtained. For patients who recieved DES, a dual antiplatelet therapy regimen comparising aspirin (100 mg/day) and clopidogrel (75 mg/day) was recommended for a minimum duration of 12 months. Subsequently, aspirin (100 mg/day) was continued indefinitely thereafter.

OCT imaging and analysis

OCT image acquisition was conducted using commercially available frequency-domain OCT imaging systems (C7XR, Illumien or Illumien Optis), as previously described [8]. The procedure was performed by an intervention cardiologist. To ensure optimal image quality, we employed a technique where the coronary blood flow was displaced by continuous flushing with contrast media manually injected directly from the guiding catheter. This created a blood-free environment conducive to clear imaging. The OCT images were acquired with an automated pullback at a speed of 36 mm/s, with cross-sectional images generated at a rotational speed of 180 frames/s. The total length of OCT pullback was 75 mm. Subsequently, the OCT images were digitally stored for offline analysis.

Qualitative and quantitative assessments of neointima were conducted using OCT at the minimal lumen area (MLA) site as well as at 5 mm proximal and 5 mm distal locations. The reference site for analysis was determined as the area with the largest lumen area either proximal or distal to the stenosis [8]. Semiautomatic measurements were performed to determine the reference lumen diameter, area of the proximal or distal site, and AS. The profiles of the stent and lumen were manually traced. Neointimal tissue characteristics were categorized as either homogeneous or heterogeneous neointima. Homogeneous neointima was defined as exhibiting high reflection and a relatively uniform signal with no local signal attenuation. On the other hand, heterogeneous neointima was defined as low reflection with an uneven signal and local signal attenuation. Neoatherosclerosis was defined as the presence of one or more of the following: macrophage infiltration, lipid-laden tissue within the stent or neointimal calcifcation [9]. Thin-cap fibroatheroma (TCFA) was defined as a fibrous cap thickness at the thinnest part of < 65µm and an angle of lipidic tissue > 180° [10]. Calcification was defined as a well-delineated, signal-poor region with sharp borders [11]. Neointimal rupture was defined as discontinuity of the neointima with or withoout a cavity formed. A lipid plaque was defined as a low-signal region with a diffuse border. A microvessel was defined as a no-signal tubulo luminal structure without a connection to the vessel lumen recognized on ≥ 3 consecutive cross-sections. Macrophage infltration was defined as signal-rich, distinct, or confluent punctate regions that exceeded the intensity of background speckle noise at in visual estimation [8]. Cholesterol crystals was defined as thin linear regions with a high reflection [8]. The thrombus was categorized as erythrocyte-rich (red) thrombus or platelet-rich (white) thrombus. Red thrombus was defined as highly backscattering with high attenuation whereas white thrombus was defined as less backscattering, and homogeneous with low attenuation [12]. Representative OCT images are provided in Fig. 2. The OCT images were analyzed by an experienced physicians (L.Z.J) who, remained to the clinical information, PCI procedure characteristics and angiographic findings.

Statistical analysis

Patients were categorized into three groups based on area stenosis (AS): AS < 70%, 70% ≤ AS < 80% and AS ≥ 80%. Continuous variables with normal distribution were expressed as mean ± standard deviation or median (interquartile range [IQR]) when abnormally distributed and compared using analysis of variance or the Kruskal Wallis test. Categorical data were presented as counts (proportions) and were compared using the χ2 test or Fisher’s exact test. Moreover, after adjusting confounding characteristics of age, sex, hypertension, diabetes mellitus, dyslipidaemia, smoking, stroke, chronic kidney disease, previous MI, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, estimated glomerular filtration rate, fasting blood-glucose, homocysteine, homogeneous neointima, heterogeneous neointima, in-stent atherosclerotic, lipid-rich plaque, TCFA-like pattern, calcification, peri-strut microvessels, intra-intima microvessels, neointima rupture, red thrombus, white thrombus, cholesterol crystal, ISR clinical presentation and medicines at discharge, data were analyzed by using ordinal logistic regression. Age, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, estimated glomerular filtration rate, fasting blood-glucose and homocysteine was considered as continuous variables rather than categorical variables. The p-value for parallel line test was 0.885. A two-sided p-value of < 0.05 was considered statistically signifificant. Statistical analyses were performed using the SPSS version 26.0 software (IBM, Armonk, New, USA).

Clinical characteristics and angiographic findings

Among the cohort of 230 patients, a total of 262 lesions were diagnosed with ISR through coronary angiography by an experienced cardiologist, 11.3% had < 70% lumen area stenosis, 51.7% had 70%-80% and 37.0% had ≥ 80% lumen AS. The baseline characteristics of patients in each AS group are presented in Table 1. The prevelance of stable angina at initial symptom onset was found to be 61.5% for AS < 70%, 47.2% for 70% ≤ AS < 80% and 31.8% for AS ≥ 80%. Notably, the incidence of stable angina decreased significantly with more advanced AS. No significant differences were observed in AS severity with respect to age, sex, coronary risk factors and laboratory data.

Table 1

Patient characteristics and coronary angiography findings
	AS＜70% (n = 26)	70%≤AS＜80% (n = 119)	AS ≥ 80% (n = 85)	P Value
Age, years, mean ± SD	63.8 ± 8.9	63.2 ± 10.3	63.1 ± 11.0	0.957
Male, n (%)	22(84.6)	94(79.0)	68(80.0)	0.810
LVEF, %	53.4 ± 11.4	53.0 ± 11.1	52.3 ± 10.2	0.871
Heart rate	83.3 ± 17.4	77.2 ± 11.4	76.1 ± 12.9	0.042
SBP(mmHg)	127.2 ± 20.4	131.9 ± 20.5	128.8 ± 21.9	0.428
DBP(mmHg)	76.6 ± 12.8	79.4 ± 11.6	78.7 ± 12.6	0.543
Coronary risk factors, n (%)
Hypertension	16 (61.5)	64 (53.8)	57 (67.1)	0.159
Diabetes mellitus	5(19.2)	29(24.4)	24(28.2)	0.622
Dyslipidaemia	12(46.2)	36(30.3)	16(18.8)	0.017
CKD	7(26.9)	27(22.7)	18(21.4)	0.834
Stroke	1(3.8)	5(4.2)	5(5.9)	0.834
Smoking	18(69.2)	57(47.2)	39(45.9)	0.099
Previous MI	9(34.6)	27(22.7)	20(23.5)	0.428
Laboratory data
TC, mmol/L	4.0 ± 1.2	4.1 ± 1.6	4.2 ± 1.4	0.831
Triglyceride, mmol/L	1.9 ± 1.1	1.9 ± 1.2	1.9 ± 1.2	0.937
LDL-C, mmol/L	2.4 ± 0.8	2.3 ± 1.0	2.4 ± 0.9	0.836
HDL-C, mmol/L	1.1 ± 0.3	1.1 ± 0.3	1.1 ± 0.3	0.702
FBG, mmol/L	7.9 ± 5.5	7.1 ± 3.4	7.4 ± 3.5	0.660
Uric acid, umol/L	394.0 ± 106.5	375.5 ± 118.7	383.7 ± 117.6	0.753
eGFR, mL/min/1.73 m2	77.1 ± 26.6	81.3 ± 22.7	79.1 ± 26.9	0.674
Homocysteine, g/L	136.5 ± 19.7	141.8 ± 17.1	138.6 ± 17.5	0.275
NT-proBNP, pg/ml	166.1 (53.0, 886.6)	197.3 (85.9, 629.5)	207.4 (91.8, 606.5)	0.867
Hs-cTnT, ng/ml	13.0 (9.1, 20.0)	12.8 (7.9, 26.4)	15.7 (9.1, 55.3)	0.200
ISR clinical presentation
Stable angina	16 (61.5)	57(47.2)	27(31.8)	0.010
UA	7(26.9)	47(39.5)	41(48.2)	0.131
NSTEMI	0(0)	6(5.0)	3(3.5)	0.289
STEMI	3(11.5)	9(7.6)	14(16.5)	0.144
Medicines at discharge
Aspirin	22(84.6)	98(82.4)	65(76.5)	0.493
P2Y12 inhibitor	21(80.8)	96(80.7)	67(78.8)	0.943
b-Blocker	19(73.1)	90(75.6)	63(74.1)	0.949
Statin	23(88.5)	90(75.6)	58(68.2)	0.106
Previous stent type
First-generation DES	16 (61.5)	78(65.4)	50(58.8)	0.615
New-generation DES	10(38.5)	41(54.6)	35(41.2)	0.615
Stents time (days)	1095(365, 1825)	1420 (730, 2555)	1605 (365, 2281)	0.259
Angiographic characteristics
ISR angiographic classification, n (%)
Focal	14(53.8)	54(45.4)	46(54.1)	0.421
Diffuse	12(46.2)	41(54.6)	39(45.9)	0.421
Target vessel, n (%)
LAD	13(50)	77(64.7)	60(70.6)	0.153
RCA	11(42.3)	32(26.9)	23(27.1)	0.265
LCX	4(15.4)	22(18.5)	20(23.5)	0.555
RVD(proximal)	3.2 ± 0.4	3.2 ± 0.5	3.2 ± 0.5	0.897
RVD(distal)	2.6 ± 0.5	2.6 ± 0.5	2.4 ± 0.5	0.006
DS,%	51.4 ± 5.2	55.7 ± 4.8	62.4 ± 5.4	＜0.001
MLD(mm )	1.8 ± 0.4	1.5 ± 0.2	1.2 ± 0.2	＜0.001
Values expressed as n (%), mean ± SD. P values are for the ANOVA or the Mann-Whitney U test for continuous variables and χ2 test or Fisher exact test for categorical data.
SBP, systolic blood pressure; DBP, diastolic blood pressure; CKD, chronic kidney disease; LAD, left anterior descending artery; LCX, left circumflex artery; FBG, fasting blood-glucose; TC, total cholesterol; TG, triglyceride; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; pro-BNP, pro-type B natriuretic peptide; Hs-cTnI, Hypersensitive cardiac troponin I; RCA, right coronary artery; DS, diameter stenosis; RVD, reference vessel diameter; MLD, minimal lumen diameter; UA, Unstable angina; NSTEMI, Non-ST-elevation myocardial infarction; STEMI, ST-elevation myocardial infarction.

Angiographic analysis revealed that, in comparison to the other four AS groups, individuals with AS ≥ 80% exhibited a smaller distal reference vessel diameter (RVD) (2.6 ± 0.5 mm vs. 2.6 ± 0.5 mm vs. 2.4 ± 0.5 mm, P = 0.006). Additionallly, the diameter stenosis of percentages for the various AS groups were 51.4% ± 5.2%, 55.7.0% ± 4.8%, 62.4% ± 5.4%, respectively (P < 0.001). Furthermore, the minimal lumen diameter in the different AS groups were recored as 1.8 ± 0.4mm, 1.5 ± 0.2mm and 1.2 ± 0.2mm, respectively (P < 0.001). However, no significant relationship was observed between the degree of AS and lesion distribution.

OCT Findings

The OCT findings have been summarized in in Table 2. It is observed that the prevalence of various indicators such as heterogeneous neointima, ISNA, LRP, neointima rupture, TCFA-like pattern, macrophage infiltration, red and white thrombus all demonstrate an increase with the progressive area narrowing (Fig. 3). The minimal lumen area within the subgroups were measured to be 3.0 ± 0.8mm², 2.0 ± 0.5mm² and 1.3 ± 0.4mm², respectively (P < 0.001). These results suggest a statistically significant association between the degree of area narrowing and the measured parameters.

Table 2

OCT findings in different area stenosis groups
	AS＜70% (n = 26)	70%≤AS＜80% (n = 119)	AS ≥ 80% (n = 85)	P Value
Qualitative, n(%)
homogeneous	6(23.1)	28(23.5)	27(31.8)	0.386
heterogeneous	12(46.2)	93(78.2)	65(76.5)	0.003
ISNA	8(30.8)	70(58.8)	43(50.6)	0.031
LRP	8(30.8)	71(59.7)	51(60)	0.019
Neointima rupture	4(15.4)	50(42.4)	33(38.8)	0.039
TCFA-like pattern	2(7.7)	17(14.4)	23(27.1)	0.022
Calcification	7(26.9)	39(33.1)	31(36.5)	0.654
Peri-strut microvessels	5(19.2)	52(44.1)	28(32.9)	0.036
Intra-intima microvessels	7(26.9)	50(42.4)	35(41.2)	0.338
Macrophage infltration	0(0)	14(11.8)	13(15.3)	0.023
Cholesterol crystal	2(7.7)	23(19.3)	13(15.3)	0.326
Malapposition	5(19.2)	21(17.9)	17(20)	0.896
Thrombus
Red	3(11.5)	20(16.8)	31(36.5)	0.002
White	4(15.4)	38(31.9)	39(45.9)	0.010
Quantitative
RVA(proximal)	7.7 ± 2.1	8.4 ± 2.2	8.2 ± 2.4	0.343
RVA(distal)	5.4 ± 1.9	5.1 ± 2.2	4.4 ± 1.7	0.014
AS,%	62.1 ± 5.5	76.3 ± 2.3	84.5 ± 3.3	＜0.001
MLA(mm2 )	3.0 ± 0.8	2.0 ± 0.5	1.3 ± 0.4	＜0.001
stent diameter (mm )	2.9 ± 0.4	2.9 ± 0.5	2.9 ± 0,5	0.523
stent area (mm2 )	6.7 ± 1.6	6.6 ± 2.2	6.8 ± 2.2	0.525
Values expressed as n (%), mean ± SD.
ISNA, in-stent atherosclerotic; LRP, lipid-rich plaque; MLA, minimal lumen area; OCT, optical coherence tomography; RLA, reference lumen area; TCFA, thin cap fibroatheroma; AS, area stenosis.

Predictors of higher AS

The results of ordinal logistic regression analysis are presented in Table S1. The analysis revealed that previous dyslipidaemia showed a significant association with increased odds of AS (odds ratio [OR], 6.706; 95% confidence interval [CI], 1.764–25.483, P = 0.005). Similarly, neointima rupture demonstrated an independent association with higher AS (OR: 4.472; 95% CI, 1.228–16.281, P = 0.023). These findings are depicted in Fig. 4.

The current study contributes valuable evidence regarding the morphological features of ISR in relation to varing degree of lumen area narrowing, utilizing OCT imaging. The primary findings of this investigation revealed that as the percentage of AS increases, there is a notable escalation in several morphological characteristics. Specifically, there is an observed rise in the prevenlace of heterogeneous neointima, ISNA, LRP, neointima rupture, TCFA-like pattern, macrophage infiltration, red and white thrombus. Furthormore, our study demonstrate a substantial association between previous dyslipidaemia and neointima rupture with the progression of ISR lesion. These findings underscore the significance of considering the extent of lumen area narrowing when evaluating and characterizing ISR. The observed augmentation in various morphological features with higher AS implies a potential correlation between the severity of ISR and these specific characteristics. Importantly, the identified associations between previous dyslipidemia and neointima rupture with the progression of ISR provide further evidence of the involvement of these factors in the development and exacerbation of ISR.

Lumen area stenosis and morphological characteristics

A previous study on ISR after bare-metal stent (BMS) implantation reported that ISR had a higher prevalence of heterogeneous neointima, occurring in the very late phase (≤ 1 year) of ISR, very late (> 5 years, without restenosis within the first year) [7]. Another study conducted by Habara et al. [6] examined 86 patients with ISR after the implantation of first generation DES and explored the morphological characteristics of early-stage (< 1 year; E-ISR), late-stage (1– 3 years; L-ISR), and very late-stage (> 3 years; VL-ISR) ISR. The result suggested a tendency for the appearance of heterogeneous neointima at a later stage of ISR. Similarlly, Hiroyuki Jinnouchi et al. [5] also reported asimilar phenomenon, with a higher prevalence of heterogeneous neointima in the late phase (> 1 year, n = 23) compared to the early phase (within 1 year, n = 30) of ISR follwing second-generation DES implantation. Feng et al. [13] also observed a higher frequency of AS ≥ 75% in the L-ISR group rather than in the E-ISR group.

Consistent with these previous findings,, our study indentified an increase trend in the percentage of AS in ISR cases,. Although the difference was not statistically significant, the incidence of heterogeneous neointima appeared to rise as well (Figure S1). This trend suggests that the longer the stent remains implanted, the higher the likelihood of heterogeneous neointima occurrence. This observation may contribute to the progression of ISR. It is worth noting that the absence of statistical significance in our study may be attributed to the small sample size.

Moreover, numerous studies have investigated the relationship between plaque morphology and severity of coronary lesion with coronary artery disease. For instance, Chao Fang et al. [14] discovered that patients with an ≥ 75% had higher prevalence of lipid-rich plaques, macrophage infiltration, microvessels, cholesterol crystals, and calcification compared to those with AS < 50% and 50% ≤ AS < 75%. In the CLIMA study [15], it was found that patients with non-culprit LAD lesion and high-risk plaque identified by OCT (including MLA < 3.5 mm2, fibrous cap thickness < 75 mm, lipid arc circumferential extension > 180°and macrophage infiltration) had a greater prevalence of major adeverse coronary events. Another study [16] investigated the characteristics of nonculprit plaque in patients with acute coronary symdrom and revealed that nonculprit plaque with culprit plaque rupture displayed a higher incidence of macrophage accumulation, microvessels and greater maximal lipid arc and higher AS compared to the culprit plaque erosion. These previous studies align with our findings.

In our present study, we included patients with ISR who underwent OCT imaging, and we categorized them into three groups based on the degree of AS. Our investigating aim to explore the impact of AS on morphological characteristics by using OCT. Our results indicate that as the percentage of AS increases in ISR, there is an accompanying rise in the incidence of heterogeneous neointima, ISNA, LRP, neointima rupture, TCFA-like pattern, macrophage infiltration.

Furthermore, our study suggested that the occurrence of both red and white thrombi increases with higher percentage of AS. This observation can be attributed to the local eddy currents and shear stresses that develop as blood flows through the stenotic site. These hemodynamic forces can displace platelets and adhesion proteins near the vessel wall. Adhesion proteins, such as the von Willebrand factor (vWF) and fibrinogen, can further trigger a cascade of clot formation, eventually leading to thrombus formation and stent occlusion [17]. Therefore, as the extent of stenosis increases, thrombus formation becomes more pronounced.

Previous dyslipidaemia and neointima rupture was associated with higher area stenosis

Previous studies have explored the association between plaque rupture and lesion progression in patients with ACS. For instance, Keisuke Satogami et al. [18] observed that STEMI patients with plaque rupture had a higher prevalence of transmural extent of infarction compared to those with plaque erosion. Another study utilized a combining OCT and intravascular ultrasound to evaluate the morphological characteristics in patients with STEMI. The findings indicated a higher ratio of microvascular damage in patients with plaque rupture than those with plaque erosion or calcifified nodule [19]. Our study also revealedthat neointima rupture was associated with higher AS, which was consistent with the previous research. Ruptured plaques trigger more severe inflammatory reactions compared to non-ruptured plaques [20, 21]. Inflflammatory cytokine can induce coronary artery constriction, which may contributed to lesion progression.

The role of blood lipid metabolism in ISR has also been invetigated. Sylvia Otto et al. [22] found a negative association between lathosterol-to-cholesterol ratio, a marker of cholesterol synthesis, and the AS in ISR (r = -0.271, P = 0.043). However, there was no significant association between ISR and total cholesterol, LDL, HDL or triglycerides. Another study [23] demostared that a low LDL-C/Apo B ratio (≤ 1.2) was strongly linked to neointimal proliferation and neointimal instability after everolimus-eluting stent implantation, as assessed by OCT and coronary angioscopy, suggesting the involvement of dyslipidaemia in the progression of ISR. In our present study, we observed a declining prevalence of previous dyslipidaemia with an increase in AS. However, there was no difference in total cholesterol, triglycerides, LDL or HDL among AS groups. Interestingly, in ordinal logistic regression analysis, we found a positive correlation between previous dyslipidaemia and the progression of ISR lesion. Additionally, we also observed an increase in the proportion of patients taking medication for dyslipidemia. However, the use of statin for dyslipidaemia at discharge was not associated with AS, which may be due to the limited sample size. Therefore, further investigations with larger sample size is needed to illustrated the association between medication for dyslipidaemia and the progression of ISR lesions.

Study limitations

This study exhibits several limitations. Firstly, it shoud be noted that this investigation was a retrospective single-center study, which introduces the possibility of selection bias that cannot be entirely disregared. Secondly, the sample size employed was relatively limited, warranting the need for a more expansive, large-scale investigation to corrobarate. Thirdly, the acquistion of data pertaing to the correlation between OCT images of ISR tissue and histological findings was insufficient. Consequently, caution should be exercised when interpreting OCT findings in relation to intimal tissue. Additional studies that provide a more extensive collection of data in this area are essential for a more definitive understanding.

In conclusion, our study advances our understanding of ISR by providing evidence regarding the morphological characteristics associated with varying degrees of lumen area narrowing. The findings emphasize the importance of considering previous dyslipidemia and neointima rupture as significant factors in the progression of ISR lesions. Future investigations can build upon these findings to enhance our knowledge of the pathophysiology and potential therapeutic interventions for ISR.

Funding

This research was supported by grants from the National Natural Science Foundation of China (82200290), the Science and Technology Program of the Guizhou Province (LC[2021] 026), the Basic Research Program of the Department of Science and Technology of Guizhou Province (Qiankehe Foundation-ZK [2022] General 671 and Qiankehe Foundation-ZK [2023] General 564), the Excellent Young Talent Cultivation Project of Zunyi City (Zunshi Kehe HZ (2022) 366) and the Master Research Foundation of the Affiliated Hospital of Zunyi Medical University [(2016) 32].

Statement of Ethics

This is an retrospective study. The Zunyi Medical University Research Ethics Committee has confirmed that no ethical approval is required.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Author Contribution

Bei Shi, Ranzun Zhao, Yongchao Zhao, and Wei Zhang designed the study. Wei Zhang, Youcheng Shen and Zhijiang Liu completed the data collecting and analyzing. Ning Gu, Jidong Rong, Chancui Deng, Xi Wang, Deng Yi, Shuai Ma, Shuangya Yang, Lei Chen and Xingwei Hu participated in part of patients demographics collection. Bei Shi, Ranzhun Zhao, Yongchao Zhao, Wei Zhang, and Youcheng Shen wrote and revised the manuscript with contributions upon all listed authors. All authors reviewed and approved the final manuscript.

Ethics approval

This is an retrospective study. The Zunyi Medical University Research Ethics Committee has confirmed that no ethical approval is required.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Consent to publish

The authors affirm that human research participants provided informed consent for publication.

Conflict of Interest

The authors declare that they have no competing interests.

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No competing interests reported.

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published 28 Feb, 2024

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Editorial decision: Major revision
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Morphological Characteristics of In-stent Restenosis with Different Degrees of Area Stenosis: An Optical Coherence Tomography Study

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Abstract

Purpose

Methods

Results

Conclusions

Figures

Introduction

Methods

Study population

Angiographic procedure

OCT imaging and analysis

Statistical analysis

Results

Clinical characteristics and angiographic findings

OCT Findings

Predictors of higher AS

Discussion

Lumen area stenosis and morphological characteristics

Previous dyslipidaemia and neointima rupture was associated with higher area stenosis

Study limitations

Conclusions

Declarations

References

Additional Declarations

Supplementary Files

Status:

Journal Publication

Version 1