Abstract
Background
Aorto-ostial (AO) coronary interventions may be associated with multiple problems, including the potential embolization of atherothrombotic debris into the aorta and systemic circulation. Such embolization could theoretically lead to stroke or silent brain injury (SBI). In this study, we aimed to investigate whether there is an increased risk of SBI in patients undergoing AO stent implantation.
Methods
Fifty-five consecutive patients undergoing AO stenting and 55 consecutive patients undergoing non-AO stenting were included. Venous blood samples were obtained before and 12 h after the procedure to measure neuron-specific enolase (NSE), which is a sensitive marker of brain injury. Newly developed NSE elevation after the procedure in an asymptomatic patient was defined as SBI.
Results
SBI was detected in 24 (43.6%) patients in the AO stenting group and 17 (30.9%) patients in the non-AO stenting group (p = .167). Although the SBI rates were statistically comparable between the groups, the presence of significant (≥50%) AO stenosis was found to be an independent predictor of SBI in multivariate logistic regression analysis [odds ratio (OR) 2.856; 95% confidence interval (CI) 1.057-7.716; p = .038]. A longer procedure time was another independent predictor for the development of SBI (OR 1.037; 95% CI 1.005-1.069; p = .023).
Conclusion
This study suggests that AO stenting may be associated with an increased risk of SBI if the lesion in the ostium is significant.
Keywords: Aorto-ostial stenting, silent brain injury, neuron-specific enolase
Introduction
Aorto-ostial (AO) coronary interventions present many challenges for interventional cardiologists. Some of these challenges include inability to engage, pressure dampening, difficulty in stent placement and inability to re-engage after stent implantation [1]. Another possible problem that may be associated with AO interventions is the potential embolization of atherothrombotic debris into the aorta and systemic circulation. Such embolization could theoretically lead to stroke or silent brain injury (SBI). The definition of SBI is based on evidence of neuronal injury in the absence of clinically apparent stroke or transient ischemic attack (TIA) [2]. Evidence of neuronal injury can be demonstrated mainly with the use of imaging modalities [2] but an acute injury can also be detected by biochemical markers such as neuron-specific enolase (NSE) [3]. NSE is an intracytoplasmic enzyme found in neurons that can be detected in serum approximately 2 h after acute neuronal injury, reaches a peak level at about 12 h, and remains positive for about 3 days [4]. Serum NSE levels have been employed to predict acute brain injury in various conditions affecting the brain directly (e.g. stroke and traumatic brain injury) or indirectly (e.g. cardiac arrest, cardiopulmonary bypass, and neonatal hypoxia) [3–11]. The risk of SBI detected by serum NSE elevation has been shown to increase in patients undergoing coronary stent implantation for acute or chronic coronary syndromes [12–16]. In this study, we aimed to investigate whether there is a further increased risk of SBI in patients undergoing AO stent implantation and to identify baseline and procedural characteristics that may be associated with the development of SBI.
Methods
Fifty-five consecutive patients who underwent AO stenting and 55 consecutive patients who underwent non-AO stenting were included in this prospective, single-centre, observational study. The AO stenting group consisted of patients with ≥70% stenosis in whom the stent protruded 1-2 mm into the aorta according to the operator’s decision for complete coverage of the plaque in the ostium (Figure 1). The non-AO stenting group consisted of patients with ≥70% stenosis who underwent stent implantation in a coronary vessel, but not within 3 mm of the aortic ostia. The exclusion criteria were as follows: baseline NSE elevation, ST-segment elevation myocardial infarction, hemodynamic instability, left ventricular ejection fraction (LVEF) <40%, severe aortic stenosis, chronic total occlusion (CTO) as the target lesion, percutaneous treatment of multiple unrelated lesions, atrial fibrillation, prior stroke or TIA, degenerative central nervous system (CNS) disorders, CNS or neuroendocrine tumours and symptomatic peripheral arterial diseases.
Figure 1.
(a). Critical lesion involving the proximal and mid segments of the RCA with approximately 30% stenosis in the ostium.
RCA, right coronary artery. (b). The RCA after the implantation of 2 stents overlapping. The proximal stent was protruded 1-2 mm into the aorta for complete coverage of the plaque in the ostium.
RCA, right coronary artery.
The baseline patient characteristics were recorded. Age, sex, smoking status and body mass index were noted. History of hypertension, diabetes, prior myocardial infarction, prior percutaneous coronary intervention (PCI) and prior coronary artery bypass grafting (CABG) were assessed. Glycated haemoglobin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglyceride levels at presentation were noted. The glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease formula. Patients with GFR <60 mL/min/1.73 m2 for at least 3 months were considered to have chronic kidney disease [17]. LVEF was calculated using the modified Simpson method. The diagnosis at admission was recorded as non-ST-segment elevation acute coronary syndrome or chronic coronary syndrome.
Aspirin (300 mg) was given orally to all patients at admission. The P2Y12 inhibitor was loaded after imaging of the coronary anatomy. Unfractionated heparin 70/100 IU/kg was administered at the beginning of PCI to obtain activated clotting times of 250–350 s. Pre-dilation and post-dilation were performed in all target lesions. Additionally, in all patients undergoing AO stent implantation, ostium flaring was performed by inflating a balloon half-way in the stent and half-way in the aorta [1]. Access site, P2Y12 inhibitor choice, guiding catheter size, number and length of stents implanted, kissing balloon (KB) inflation or bifurcation stenting (BS) with two stents if necessary were left to the operator’s discretion. The number of diseased vessels was defined as the number of major epicardial coronary arteries with ≥50% stenosis and was recorded as 1, 2 or 3. Diameter stenosis was assessed visually. Significant AO stenosis was defined as ≥50% stenosis within 3 mm of the orifice engaged by the guiding catheter. Calcification more than just spots in the ostium engaged by the guiding catheter was noted as moderate or severe AO calcification [18]. The reference vessel diameter (RVD) was accepted as the diameter reached by the stent or post-dilation balloon, whichever was higher. The target vessel, native or in-stent target lesion, contrast volume, and procedure time were also recorded.
Venous blood samples were obtained before and 12 h after the procedure for NSE measurements. NSE levels were measured using a human NSE enzyme-linked immunosorbent assay (ELISA) kit (Sunredbio, Shanghai, China). The absolute change in NSE was calculated by subtracting the baseline NSE level from the postprocedural NSE level. The intra- and inter-assay coefficients of variability were <10% and <12%, respectively. The upper reference limit of normal for the kits, determined by the manufacturer, was 20 ng/mL. NSE within normal limits before the procedure and >20 ng/mL after the procedure in an asymptomatic patient was defined as SBI.
The research data were uploaded and analysed using the Statistical Package for Social Sciences (SPSS) version 25, for which a copyright license was obtained. Descriptive statistics for categorical variables are presented as frequencies and percentages. The chi-square test or Fisher’s exact test in case of any cells with an expected count of less than 5 in the crosstabs, was used to compare categorical variables. The Kolmogorov–Smirnov test was applied to determine whether the numerical variables were normally distributed. Descriptive statistics are expressed as mean ± standard deviation for numerical variables with a normal distribution and as median (minimum-maximum) for those without a normal distribution. An independent samples t-test was used to compare numerical variables with a normal distribution, and Levene’s test was utilized to check the equality of variances. The Mann–Whitney U-test was used to compare numerical variables without a normal distribution. Multivariate logistic regression analysis was performed to identify the independent predictors of NSE elevation after the procedure. All baseline and procedural characteristics evaluated in the study were subjected to univariate analysis, and variables with p < 0.1 in the univariate analysis were subjected to multivariate analysis. In this study, no data were missing, and the statistical significance level was set at p < 0.05.
Results
The stenting procedure was successful in all patients included in the study, with <30% residual stenosis and Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow. TIA, stroke, or death were not observed in any of the patients during hospitalization, and no patients were subjected to magnetic resonance imaging (MRI) after PCI.
SBI was detected in 24 (43.6%) patients in the AO stenting group and 17 (30.9%) patients in the non-AO stenting group (p = 0.167). The baseline NSE was similar between the groups, but the postprocedural NSE and the absolute change in NSE were significantly higher in the AO stenting group (p = 0.021 and p = 0.007, respectively). The baseline characteristics of the AO and non-AO stenting groups were comparable. Among the procedural characteristics, access site, number of diseased vessels, native or in-stent target lesion, diameter stenosis, moderate or severe AO calcification, guiding catheter size, total stent length per lesion, KB inflation, BS with 2 stents, and procedure time were similar. The target vessel was the right coronary artery (RCA) in 31 (56.4%), left main coronary artery (LM) in 22 (40.0%), and saphenous vein graft (SVG) in 2 (3.6%) patients in the AO stenting group, whereas it was the left anterior descending artery in 22 (40.0%), left circumflex artery in 15 (27.3%), RCA in 15 (27.3%), LM in 2 (3.6%), and SVG in 1 (1.8%) patient in the non-AO stenting group (p <. 001). Significant AO stenosis was present in 22 (40.0%) patients in the AO stenting group, but none of the patients in the non-AO stenting group had significant AO stenosis (p <. 001). The P2Y12 inhibitor was significantly different between the groups (p = .015). The RVD, number of stents per lesion, and contrast volume were significantly higher in the AO stenting group (p <. 001, p = .019, and p = .031, respectively) (Table 1).
Table 1.
Comparison of baseline and procedural characteristics, and SBI rates of AO and non-AO stenting groups.
| Variable | AO stenting (n = 55) | Non-AO stenting (n = 55) | P | |
|---|---|---|---|---|
| Age (year) | 64.3 ± 10.6 | 64.2 ± 8.6 | 0.968 | |
| Sex | Male (%*) | 30 (54.5) | 35 (63.6) | 0.332 |
| Female (%*) | 25 (45.5) | 20 (36.4) | ||
| Smoking | Current (%*) | 15 (27.3) | 13 (23.6) | 0.628 |
| Past (%*) | 15 (27.3) | 12 (21.8) | ||
| Never (%*) | 25 (45.5) | 30 (54.5) | ||
| Hypertension (%*) | 32 (58.2) | 36 (65.5) | 0.432 | |
| Diabetes (%*) | 27 (49.1) | 27 (49.1) | 1.000 | |
| HbA1c (%) | 6.0 (5.1-11.6) | 6.3 (5.3-12.9) | 0.108 | |
| Total cholesterol (mg/dL) | 185.2 ± 48.6 | 176.1 ± 46.6 | 0.337 | |
| LDL cholesterol (mg/dL) | 113.7 ± 45.1 | 101.7 ± 40.5 | 0.159 | |
| HDL cholesterol (mg/dL) | 41 (22–67) | 40 (22–88) | 0.311 | |
| Triglyceride (mg/dL) | 123 (47–1145) | 136 (65–461) | 0.114 | |
| Body mass index (kg/m2) | 27.5 (19.6–37.1) | 27.6 (21.6–39.0) | 0.335 | |
| Chronic kidney disease (%*) | 10 (18.2) | 8 (14.5) | 0.606 | |
| GFR (mL/min/1.73 m2) | 82.4 ± 22.4 | 83.1 ± 22.6 | 0.866 | |
| Prior MI (%*) | 26 (47.3) | 20 (36.4) | 0.246 | |
| Prior PCI (%*) | 22 (40.0) | 26 (47.3) | 0.442 | |
| Prior CABG (%*) | 9 (16.4) | 3 (5.5) | 0.067 | |
| LVEF (%) | 55 (40-73) | 55 (40-70) | 0.505 | |
| Diagnosis at admission | NSTE-ACS (%*) | 19 (34.5) | 17 (30.9) | 0.684 |
| CCS (%*) | 36 (65.5) | 38 (69.1) | ||
| Access site | Radial (%*) | 26 (47.3) | 33 (60.0) | 0.181 |
| Femoral (%*) | 29 (52.7) | 22 (40.0) | ||
| Number of diseased vessels | 1 (%*) | 20 (36.4) | 30 (54.5) | 0.152 |
| 2 (%*) | 30 (54.5) | 22 (40.0) | ||
| 3 (%*) | 5 (9.1) | 3 (5.5) | ||
| Target vessel | LM (%*) | 22 (40.0) | 2 (3.6) | <0.001 |
| LAD (%*) | 0 | 22 (40.0) | ||
| LCX (%*) | 0 | 15 (27.3) | ||
| RCA (%*) | 31 (56.4) | 15 (27.3) | ||
| SVG (%*) | 2 (3.6) | 1 (1.8) | ||
| Native/in-stent | Native (%*) | 53 (96.4) | 51 (92.7) | 0.679 |
| In-stent (%*) | 2 (3.6) | 4 (7.3) | ||
| Diameter stenosis (%) | 85 (70–100) | 90 (70–100) | 0.552 | |
| Significant AO stenosis (%*) | 22 (40.0) | 0 | <0.001 | |
| Moderate or severe AO calcification (%*) | 5 (9.1) | 3 (5.5) | 0.716 | |
| P2Y12 inhibitor | Prasugrel (%*) | 17 (30.9) | 5 (9.1) | 0.015 |
| Ticagrelor (%*) | 6 (10.9) | 6 (10.9) | ||
| Clopidogrel (%*) | 32 (58.2) | 44 (80.0) | ||
| Guiding catheter size | 6Fr (%*) | 37 (67.3) | 42 (76.4) | 0.289 |
| 7Fr (%*) | 18 (32.7) | 13 (23.6) | ||
| Reference vessel diameter (mm) | 4.3 (2.8–5.7) | 3.3 (2.7–5.2) | <0.001 | |
| Number of stents per lesion | 1.4 ± 0.6 | 1.2 ± 0.4 | 0.019 | |
| Total stent length per lesion (mm) | 32 (12–81) | 23 (12–78) | 0.090 | |
| KB inflation (%*) | 10 (18.2) | 7 (12.7) | 0.429 | |
| BS with 2 stents (%*) | 4 (7.3) | 4 (7.3) | 1.000 | |
| Contrast volume (mL) | 130 (50-230) | 100 (40-270) | 0.031 | |
| Procedure time (min) | 33.8 ± 14.4 | 31.9 ± 14.1 | 0.493 | |
| Baseline NSE (ng/ mL) | 9.76 ± 3.28 | 9.24 ± 3.28 | 0.413 | |
| Postprocedural NSE (ng/ mL) | 16.3 (3.8-86.1) | 10.4 (3.2-88.2) | 0.021 | |
| Absolute change in NSE (ng/ mL) | 5.9 (−1.8–71.3) | 0.1 (−1.8–78.9) | 0.007 | |
| SBI (%*) | 24 (43.6) | 17 (30.9) | 0.167 | |
AO: aorto-ostial; BS: bifurcation stenting; CABG: coronary artery bypass grafting; CCS: chronic coronary syndrome; Fr: French; GFR: glomerular filtration rate; HbA1c: glycated haemoglobin; HDL: high-density lipoprotein; KB: kissing balloon; LAD: left anterior descending artery; LCX: left circumflex artery; LDL: low-density lipoprotein; LM: left main coronary artery; LVEF: left ventricular ejection fraction; MI: myocardial infarction; NSE: neuron-specific enolase; NSTE-ACS: non-ST-segment elevation acute coronary syndrome; PCI: percutaneous coronary intervention; RCA: right coronary artery; SBI: silent brain injury; SVG: saphenous vein graft.
Column percentage.
When comparing the baseline and procedural characteristics of patients with and without SBI, patients with SBI were more likely to have significant AO stenosis and longer procedure times (p = 0.018 and p = 0.025, respectively) (Table 2).
Table 2.
Comparison of baseline and procedural characteristics of patients with and without SBI.
| Variable | SBI (+) (n = 41) | SBI (-) (n = 69) | P | |
|---|---|---|---|---|
| Age (year) | 65 (39–89) | 65 (32–83) | 0.582 | |
| Sex | Male (%*) | 28 (68.3) | 37 (53.6) | 0.130 |
| Female (%*) | 13 (31.7) | 32 (46.4) | ||
| Smoking | Current (%*) | 9 (22.0) | 19 (27.5) | 0.395 |
| Past (%*) | 13 (31.7) | 14 (20.3) | ||
| Never (%*) | 19 (46.3) | 36 (52.2) | ||
| Hypertension (%*) | 23 (56.1) | 45 (65.2) | 0.341 | |
| Diabetes (%*) | 25 (61.0) | 29 (42.0) | 0.055 | |
| HbA1c (%) | 6.7 (5.2–12.9) | 6.1 (5.1–11.6) | 0.216 | |
| Total cholesterol (mg/dL) | 186.0 ± 56.6 | 177.5 ± 41.5 | 0.421 | |
| LDL cholesterol (mg/dL) | 110.3 ± 50.0 | 106.1 ± 38.8 | 0.659 | |
| HDL cholesterol (mg/dL) | 41 (22–88) | 41 (22–64) | 0.797 | |
| Triglyceride (mg/dL) | 130 (52–1145) | 131 (47–461) | 0.956 | |
| Body mass index (kg/m2) | 27.4 (21.1–37.1) | 27.6 (19.6–39.0) | 0.670 | |
| Chronic kidney disease (%*) | 8 (19.5) | 10 (14.5) | 0.491 | |
| GFR (mL/min/1.73 m2) | 83.7 ± 23.0 | 82.1 ± 22.2 | 0.734 | |
| Prior MI (%*) | 19 (46.3) | 27 (39.1) | 0.458 | |
| Prior PCI (%*) | 20 (48.8) | 28 (40.6) | 0.402 | |
| Prior CABG (%*) | 6 (14.6) | 6 (8.7) | 0.358 | |
| LVEF (%) | 51 (40–73) | 55 (40–70) | 0.278 | |
| Diagnosis at admission | NSTE-ACS (%*) | 11 (26.8) | 25 (36.2) | 0.310 |
| CCS (%*) | 30 (73.2) | 44 (63.8) | ||
| Access site | Radial (%*) | 23 (56.1) | 36 (52.2) | 0.690 |
| Femoral (%*) | 18 (43.9) | 33 (47.8) | ||
| Number of diseased vessels | 1 (%*) | 17 (41.5) | 33 (47.8) | 0.828 |
| 2 (%*) | 21 (51.2) | 31 (44.9) | ||
| 3 (%*) | 3 (7.3) | 5 (7.2) | ||
| Target vessel | LM (%*) | 8 (19.5) | 16 (23.2) | 0.405 |
| LAD (%*) | 8 (19.5) | 14 (20.3) | ||
| LCX (%*) | 3 (7.3) | 12 (17.4) | ||
| RCA (%*) | 20 (48.8) | 26 (37.7) | ||
| SVG (%*) | 2 (4.9) | 1 (1.4) | ||
| Native/in-stent | Native (%*) | 39 (95.1) | 65 (94.2) | 1.000 |
| In-stent (%*) | 2 (4.9) | 4 (5.8) | ||
| Diameter stenosis (%) | 90 (70–100) | 85 (70–100) | 0.119 | |
| Significant AO stenosis (%*) | 13 (31.7) | 9 (13.0) | 0.018 | |
| Moderate or severe AO calcification (%*) | 4 (9.8) | 4 (5.8) | 0.468 | |
| P2Y12 inhibitor | Prasugrel (%*) | 7 (17.1) | 15 (21.7) | 0.823 |
| Ticagrelor (%*) | 5 (12.2) | 7 (10.1) | ||
| Clopidogrel (%*) | 29 (70.7) | 47 (68.1) | ||
| Guiding catheter size | 6Fr (%*) | 30 (73.2) | 49 (71.0) | 0.808 |
| 7Fr (%*) | 11 (26.8) | 20 (29.0) | ||
| Reference vessel diameter (mm) | 3.8 (2.7–5.2) | 3.8 (2.7–5.7) | 0.748 | |
| Number of stents per lesion | 1.4 ± 0.6 | 1.2 ± 0.5 | 0.139 | |
| Total stent length per lesion (mm) | 28 (12-81) | 24 (12-78) | 0.178 | |
| KB inflation (%*) | 5 (12.2) | 12 (17.4) | 0.466 | |
| BS with 2 stents (%*) | 3 (7.3) | 5 (7.2) | 1.000 | |
| Contrast volume (mL) | 120 (50-230) | 110 (40-270) | 0.717 | |
| Procedure time (min) | 33 (15-92) | 29 (12-61) | 0.025 | |
AO: aorto-ostial; BS: bifurcation stenting; CABG: coronary artery bypass grafting; CCS: chronic coronary syndrome; Fr: French; GFR: glomerular filtration rate; HbA1c: glycated haemoglobin; HDL: high-density lipoprotein; KB: kissing balloon; LAD: left anterior descending artery; LCX: left circumflex artery; LDL: low-density lipoprotein; LM: left main coronary artery; LVEF: left ventricular ejection fraction; MI: myocardial infarction; NSTE-ACS: non-ST-segment elevation acute coronary syndrome; PCI: percutaneous coronary intervention; RCA: right coronary artery; SBI: silent brain injury; SVG: saphenous vein graft.
Column percentage.
Although the SBI rates were statistically comparable between the AO and non-AO stenting groups, the presence of significant AO stenosis was found to be an independent predictor of SBI development in multivariate logistic regression analysis [odds ratio (OR) 2.856; 95% confidence interval (CI) 1.057–7.716; p = 0.038]. Subgroup analysis revealed that 13 (59.1%) of 22 patients with significant AO stenosis who underwent AO stent implantation developed SBI. A longer procedure time was another independent predictor of SBI according to the multivariate analysis (OR 1.037; 95% CI 1.005–1.069; p = 0.023) (Table 3).
Table 3.
Predictors of SBI in multivariate logistic regression analysis.
| Variable | OR (95% CI) | P |
|---|---|---|
| Diabetes | 1.949 (0.851–4.463) | 0.115 |
| Significant AO stenosis | 2.856 (1.057–7.716) | 0.038 |
| Total stent length per lesion | 1.019 (0.992–1.047) | 0.171 |
| Procedure time | 1.037 (1.005–1.069) | 0.023 |
AO: aorto-taostial; CI: confidence interval; OR: odds ratio; SBI: silent brain injury.
AQ1: Please provide significance of bold values in Tables 1, 2 and 3.
Discussion
In the present study, the SBI rates were statistically comparable between patients who underwent AO and non-AO stent implantation. However, the presence of significant AO stenosis in the ostium engaged by the guiding catheter was an independent predictor of SBI. A longer procedure time was another independent predictor of SBI development.
According to the results of our study, the SBI rates tended to be higher in patients who underwent AO stent implantation, but the difference was not statistically significant. Significant AO stenosis, which was present in 40% of the patients in the AO stenting group but not in any of the patients in the non-AO stenting group, was independently associated with the development of SBI. In the AO stenting group, the SBI rate was 59.1% in patients with significant AO stenosis, whereas it was 33.3% in those without significant AO stenosis, which was very similar to the SBI rate in the non-AO stenting group. In other words, the tendency for SBI in the AO stenting group was due to a subgroup with significant AO stenosis. This may be associated with the potential embolization of atherothrombotic debris from the coronary ostium into cerebral circulation. In addition, the higher SBI rate in the subgroup with significant AO stenosis may be due to technical issues rather than the lesions themselves. Aggressive catheter manipulations to engage the ostium with significant AO stenosis may cause plaque mobilization from the ascending aorta [19]. Pressure dampening associated hypotension may play a role in the development of SBI [20]. While the catheter is disengaged from the coronary ostium to avoid pressure dampening, embolization may occur during the removal of equipment contaminated with atherothrombotic fragments. Contrast injections and even saline flush while the catheter is slightly disengaged may lead to embolization of small thrombi formed at the tip of the catheter into cerebral circulation [21]. In a similar setting, contrast-induced vasoconstriction [22] and air embolism [23] in the cerebral vessels may also contribute to the development of SBI. These are possible explanations why significant AO stenosis may be an independent predictor of SBI.
A longer procedure time was also independently associated with SBI development in our study, in line with previous studies [16,24]. It is reasonable to assume that the risk of thrombus formation and plaque mobilization may increase as the procedure is prolonged. Although not statistically significant, patients with SBI were more likely to have diabetes in our study. However, in the multivariate analysis, diabetes was not an independent predictor of SBI development. In another study we conducted previously, the rate of SBI detected by serum NSE elevation was higher when stenting CTO lesions compared with stenting non-CTO lesions (59.7% vs. 39.1%). The findings of the aforementioned study suggested that diabetes might also be an independent predictor of SBI [15].
Our findings imply that utmost care should be taken to prevent atheromatous plaque and thrombus embolization in patients with significant AO stenosis undergoing AO stent implantation. In addition, avoiding prolonged PCI procedures, if possible, may reduce the risk of SBI. The cumulative effects of SBI have been shown to be associated with various psychiatric and neurological disorders and even increased mortality [25–29]. To our knowledge, this is the first study to associate the presence of significant AO stenosis with SBI development in patients undergoing AO stent implantation.
There are extracerebral sources of NSE such as red blood cells, platelets, and lymphocytes [30,31]. The reliability of NSE as a marker for brain injury in situations where there are manipulations taking place in the bloodstream, as occurs in interventional coronary procedures, may be compromised due to the potential for contamination from blood. For instance, in the context of cardiac surgery with cardiopulmonary bypass, the elevated levels of NSE have been primarily attributed to the release of haemolysed erythrocytes [32]. Coronary stenting is a less invasive procedure, and the potential for NSE contamination from blood may be less significant. However, the possibility of invisible haemolysis still exists, which could result in elevated NSE levels [33]. This is a limitation of the study, and further research is required to elucidate this issue.
Our study also had other limitations. First, this was a single-centre study with a relatively small sample size. Second, SBI was not confirmed by MRI, which is the recommended method for detecting ischemic brain injury [2]. However, NSE has been shown to have similar efficacy to MRI in detecting brain injury, with a sensitivity of approximately 90% [5,34]. Finally, some variables with the potential to affect SBI rates were not similar between the groups. Probably because LM stenting was more common, prasugrel as the choice of P2Y12 inhibitor was more frequent in the AO stenting group compared to the non-AO stenting group. The number of stents per lesion and contrast volume were higher in the AO stenting group. Although not statistically significant, a history of prior CABG was more common, and the total stent length per lesion was higher in the AO stenting group. However, none of these variables were independently associated with SBI development according to the logistic regression analysis.
Conclusion
This study suggests that AO stenting may be associated with an increased risk of SBI if the lesion in the ostium is significant.
Funding Statement
The authors declare that no funding was received for conducting this study.
Author contributions
UY, MU, MC, BA, KS, and OG were involved in the conception and design of the work. UY, AK, AOK, AC, and BA made substantial contributions to the acquisition, analysis, or interpretation of data for the work. UY drafted the article. AK, MU, AOK, AC, MC, BA, KS, and OG revised the article critically for intellectual content. All authors approved the final version to be published. All authors agreed to be accountable for all aspects of the work.
Ethical statement
The study was approved by the Ondokuz Mayis University Clinical Research Ethics Committee (decision date: March 13, 2020; decision number: 2020/107).
Consent to participate
Written informed consent was obtained from all the patients included in the study.
Disclosure statement
The authors report there are no competing interests to declare.
Data availability statement
The data that support the findings of this study are available from the corresponding author, UY, upon reasonable request.
References
- 1.Alame A, Brilakis ES.. Best practices for treating coronary ostial lesions. Catheter Cardiovasc Interv. 2016;87(2):241–242. doi: 10.1002/ccd.26421. [DOI] [PubMed] [Google Scholar]
- 2.Sacco RL, Kasner SE, Broderick JP, American Heart Association Stroke Council, Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular and Stroke Nursing; Council on Epidemiology and Prevention; Council on Peripheral Vascular Disease; Council on Nutrition, Physical Activity and Metabolism ., et al. An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44(7):2064–2089. doi: 10.1161/STR.0b013e318296aeca. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Anand N, Stead LG.. Neuron-specific enolase as a marker for acute ischemic stroke: a systematic review. Cerebrovasc Dis. 2005;20(4):213–219. doi: 10.1159/000087701. [DOI] [PubMed] [Google Scholar]
- 4.Barone FC, Clark RK, Price WJ, et al. Neuron-specific enolase increases in cerebral and systemic circulation following focal ischemia. Brain Res. 1993;623(1):77–82. doi: 10.1016/0006-8993(93)90012-c. [DOI] [PubMed] [Google Scholar]
- 5.Oh SH, Lee JG, Na SJ, et al. Prediction of early clinical severity and extent of neuronal damage in anterior-circulation infarction using the initial serum neuron-specific enolase level. Arch Neurol. 2003;60(1):37–41. doi: 10.1001/archneur.60.1.37. [DOI] [PubMed] [Google Scholar]
- 6.Guzel A, Er U, Tatli M, et al. Serum neuron-specific enolase as a predictor of short-term outcome and its correlation with Glasgow Coma Scale in traumatic brain injury. Neurosurg Rev. 2008;31(4):439–445. doi: 10.1007/s10143-008-0148-2. [DOI] [PubMed] [Google Scholar]
- 7.Meric E, Gunduz A, Turedi S, et al. The prognostic value of neuron-specific enolase in head trauma patients. J Emerg Med. 2010;38(3):297–301. doi: 10.1016/j.jemermed.2007.11.032. [DOI] [PubMed] [Google Scholar]
- 8.Wijdicks EF, Hijdra A, Young GB, Quality Standards Subcommittee of the American Academy of Neurology ., et al. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006;67(2):203–210. doi: 10.1212/01.wnl.0000227183.21314.cd. [DOI] [PubMed] [Google Scholar]
- 9.Meynaar IA, Oudemans-van Straaten HM, van der Wetering J, et al. Serum neuron-specific enolase predicts outcome in post-anoxic coma: a prospective cohort study. Intensive Care Med. 2003;29(2):189–195. doi: 10.1007/s00134-002-1573-2. [DOI] [PubMed] [Google Scholar]
- 10.Yuan SM. Biomarkers of cerebral injury in cardiac surgery. Anadolu Kardiyol Derg. 2014; Nov14(7):638–645. doi: 10.5152/akd.2014.5321. [DOI] [PubMed] [Google Scholar]
- 11.Celtik C, Acunaş B, Oner N, et al. Neuron-specific enolase as a marker of the severity and outcome of hypoxic ischemic encephalopathy. Brain Dev. 2004;26(6):398–402. doi: 10.1016/j.braindev.2003.12.007. [DOI] [PubMed] [Google Scholar]
- 12.Aykan AÇ, Gökdeniz T, Bektaş H, et al. Assessment of Silent Neuronal Injury Following Coronary Angiography and Intervention in Patients With Acute Coronary Syndrome. Clin Appl Thromb Hemost. 2016;22(1):52–59. doi: 10.1177/1076029614532007. [DOI] [PubMed] [Google Scholar]
- 13.Goksuluk H, Gulec S, Ozcan OU, et al. Usefulness of neuron-specific enolase to detect silent neuronal ischemia after percutaneous coronary intervention. Am J Cardiol. 2016;117(12):1917–1920. doi: 10.1016/j.amjcard.2016.03.037. [DOI] [PubMed] [Google Scholar]
- 14.Göksülük H, Güleç S, Özyüncü N, et al. Comparison of frequency of silent cerebral infarction after coronary angiography and stenting with transradial versus transfemoral approaches. Am J Cardiol. 2018;122(4):548–553. doi: 10.1016/j.amjcard.2018.04.056. [DOI] [PubMed] [Google Scholar]
- 15.Uyanik M, Yildirim U, Avci B, et al. Assessment of silent brain injury in patients undergoing elective percutaneous coronary intervention due to chronic total occlusion. Scand Cardiovasc J. 2023;57(1):25–30. doi: 10.1080/14017431.2022.2150786. [DOI] [PubMed] [Google Scholar]
- 16.Arslan U, Yenerçağ M, Erdoğan G, et al. Silent cerebral infarction after percutaneous coronary intervention of chronic total occlusions (CTO) and non-CTOs. Int J Cardiovasc Imaging. 2020;36(11):2107–2113. doi: 10.1007/s10554-020-01939-w. [DOI] [PubMed] [Google Scholar]
- 17.Stevens PE, Levin A, Kidney Disease: improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members . Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013; 158(11):825–830. doi: 10.7326/0003-4819-158-11-201306040-00007. [DOI] [PubMed] [Google Scholar]
- 18.Karacsonyi J, Karmpaliotis D, Alaswad K, et al. Impact of calcium on chronic total occlusion percutaneous coronary interventions. Am J Cardiol. 2017;120(1):40–46. doi: 10.1016/j.amjcard.2017.03.263. [DOI] [PubMed] [Google Scholar]
- 19.Keeley EC, Grines CL.. Scraping of aortic debris by coronary guiding catheters: a prospective evaluation of 1,000 cases. J Am Coll Cardiol. 1998;32(7):1861–1865. doi: 10.1016/s0735-1097(98)00497-5. [DOI] [PubMed] [Google Scholar]
- 20.Klijn CJ, Kappelle LJ.. Haemodynamic stroke: clinical features, prognosis, and management. Lancet Neurol. 2010;9(10):1008–1017. doi: 10.1016/S1474-4422(10)70185-X. [DOI] [PubMed] [Google Scholar]
- 21.Bendszus M, Koltzenburg M, Burger R, et al. Silent embolism in diagnostic cerebral angiography and neurointerventional procedures: a prospective study. Lancet. 1999;354(9190):1594–1597. doi: 10.1016/S0140-6736(99)07083-X. [DOI] [PubMed] [Google Scholar]
- 22.Spina R, Simon N, Markus R, et al. Contrast-induced encephalopathy following cardiac catheterization. Catheter Cardiovasc Interv. 2017;90(2):257–268. doi: 10.1002/ccd.26871. [DOI] [PubMed] [Google Scholar]
- 23.Markus H, Loh A, Israel D, et al. Microscopic air embolism during cerebral angiography and strategies for its avoidance. Lancet. 1993;341(8848):784–787. doi: 10.1016/0140-6736(93)90561-t. [DOI] [PubMed] [Google Scholar]
- 24.Büsing KA, Schulte-Sasse C, Flüchter S, et al. Cerebral infarction: incidence and risk factors after diagnostic and interventional cardiac catheterization–prospective evaluation at diffusion-weighted MR imaging. Radiology. 2005;235(1):177–183. doi: 10.1148/radiol.2351040117. [DOI] [PubMed] [Google Scholar]
- 25.Vermeer SE, Prins ND, den Heijer T, et al. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med. 2003;348(13):1215–1222. doi: 10.1056/NEJMoa022066. [DOI] [PubMed] [Google Scholar]
- 26.Liebetrau M, Steen B, Hamann GF, et al. Silent and symptomatic infarcts on cranial computerized tomography in relation to dementia and mortality: a population-based study in 85-year-old subjects. Stroke. 2004;35(8):1816–1820. doi: 10.1161/01.STR.0000131928.47478.44. [DOI] [PubMed] [Google Scholar]
- 27.Bokura H, Kobayashi S, Yamaguchi S, et al. Silent brain infarction and subcortical white matter lesions increase the risk of stroke and mortality: a prospective cohort study. J Stroke Cerebrovasc Dis. 2006;15(2):57–63. doi: 10.1016/j.jstrokecerebrovasdis.2005.11.001. [DOI] [PubMed] [Google Scholar]
- 28.Avdibegović E, Bećirović E, Selimbasić Z, et al. Cerebral cortical atrophy and silent brain infarcts in psychiatric patients. Psychiatr Danub. 2007;19(1-2):49–55. [PubMed] [Google Scholar]
- 29.Wright CB, Festa JR, Paik MC, et al. White matter hyperintensities and subclinical infarction: associations with psychomotor speed and cognitive flexibility. Stroke. 2008;39(3):800–805. doi: 10.1161/STROKEAHA.107.484147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Påhlman S, Esscher T, Bergvall P, et al. Purification and characterization of human neuron-specific enolase: radioimmunoassay development. Tumour Biol. 1984;5(2):127–139. [PubMed] [Google Scholar]
- 31.Notomi T, Morikawa J, Kato K, et al. Radioimmunoassay development for human neuron-specific enolase: with some clinical results in lung cancers and neuroblastoma. Tumour Biol. 1985;6(1):57–66. [PubMed] [Google Scholar]
- 32.Motoyoshi N, Tsutsui M, Soman K, et al. Neuron-specific enolase levels immediately following cardiovascular surgery is modulated by hemolysis due to cardiopulmonary bypass, making it unsuitable as a brain damage biomarker. J Artif Organs. 2023;27(2):100–107. doi: 10.1007/s10047-023-01398-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Mastroianni A, Panella R, Morelli D.. Invisible hemolysis in serum samples interferes in NSE measurement. Tumori. 2020; Feb106(1):79–81. doi: 10.1177/0300891619867836. [DOI] [PubMed] [Google Scholar]
- 34.Hill MD, Jackowski G, Bayer N, et al. Biochemical markers in acute ischemic stroke. CMAJ. 2000;162(8):1139–1140. [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author, UY, upon reasonable request.