Incomplete struts coverage is a predictor of late stent thrombosis after implantation of the drug-eluting stents (DES) in atherosclerotic lesions. The process of struts coverage in DES implanted for bare-metal stent (BMS) restenosis has never been described. Thirty-two patients with stable coronary artery disease were consecutively selected, 11 with BMS restenosis (group A) and 21 with de novo atherosclerotic lesions (group B). All patients underwent everolimus-eluting stent implantation; coronary angiography and optical coherence tomography were performed at 6 months follow-up. Percentage difference in struts coverage between the 2 groups was the primary end point. A total of 85,773 struts (17,891 in group A and 67,882 in group B) were analyzed: compared with group B, the percentage of uncovered stent struts was significantly lower in group A (2.6% vs 4.8%; p <0.0001). In group A, DES struts protruding out of BMS were more uncovered (5.0% vs 1.9%; p <0.0001) and malapposed (4.1% vs 2.1%; p <0.0001) compared with overlapping struts. In conclusion, when DES are implanted to treat BMS restenosis, struts coverage at 6 months follow-up is more complete compared with DES implanted in atherosclerotic lesions.
Drug-eluting stents (DES) inhibit neointimal hyperplasia and reduce the risk of in-stent restenosis compared with bare-metal stent (BMS). Despite reduced restenosis rates, stent thrombosis (ST), a life-threatening complication of DES technology, has emerged as a major concern. ST is still an issue, although its rate decreased with the advent of second-generation DES because of the wide use of DES and the ominous clinical consequences of late thrombotic events. Studies based on pathological specimens showed that arterial healing of DES is delayed and that incomplete endothelialization is the most important morphometric predictor of ST. However, this delay in struts coverage has been extensively studied for DES implanted in native coronary lesions, but little information is available about endothelialization of DES implanted to treat BMS restenosis. The pathologic substrate of BMS restenosis is quite different from atherosclerosis. The latter may show calcium or atheromatous plaques with a fibrous cap overlying a lipid-rich core, whereas in-stent neointimal tissue mainly consists of smooth muscle cells, extracellular matrix, and macrophages and is likely to offer a more suitable environment for stent struts re-endothelialization. The aim of this study was to investigate whether stent struts coverage, assessed by optical coherence tomography (OCT) at 6 months follow-up, is more complete when DES are implanted to treat a BMS restenosis compared with atherosclerotic de novo lesions.
Methods
Twelve consecutive patients with stable angina or silent myocardial ischemia because of significant BMS restenosis and treated with everolimus-eluting stent (EES) implantation (Xience V or Xience Prime; Abbott Laboratories, Abbott Park, Illinois) were consecutively selected from November 2010 to January 2012 and constituted the study group. The control group comprised 24 consecutive patients with stable angina or silent myocardial ischemia because of significant de novo atherosclerotic lesions that were treated with EES implantation in the same time period. Exclusion criteria were acute coronary syndrome either with or without ST-segment elevation in the previous 48 hours, hemodynamic instability, contraindications to dual antiplatelet therapy, significant left main coronary artery disease, reference vessel diameter <2.5 mm, coronary anatomy unsuitable for OCT evaluation, chronic kidney disease with serum creatinine >2 mg/dl, pregnancy, allergy to contrast agent, everolimus or aspirin, life expectancy <24 months, and patients with possible low adherence to medical therapy. All patients had coronary angiography with OCT assessment of the target vessel at 6 months follow-up to assess stent struts coverage. An ethics committee approval was obtained from the Ethics Committee of the Misericordia Hospital on October 2010. The protocol was registered at ClinicalTrials.gov with the identifier number NCT01243099 .
Quantitative coronary angiography was performed offline using a quantitative coronary angiography analysis system (Xcelera; Philips Healthcare, Eindhoven, The Netherlands) by a single person blinded to patients’ information. Minimal luminal diameter of treated coronary segments, reference vessel diameter, percentage diameter stenosis, and lesion length were determined on the baseline angiogram and at 6 months follow-up. A C7-XR OCT system (St. Jude Medical, St. Paul, Minnesota) was used in this study. The OCT imaging catheters were delivered over a 0.014″ guidewire through the guiding catheter after administration of intracoronary nitrates (100 μg). For effective clearing of blood from the imaging field, angiographic contrast media was injected through the guiding catheter with an automated power injector. Specifically, injection of 14 ml of contrast at a rate <4 ml/s was sufficient to achieve an imaging time of 2 to 3 seconds consistently in all the major coronary branches. At a pull-back rate of 20 mm/s, an imaging time of 2 seconds was long enough to scan a 4-cm-long segment. Frequency-domain OCT images were calibrated adjusting the Z-offset. This critical step was performed before image acquisition to obtain accurate measurements. OCT images were analyzed applying the following established definitions: stent malapposition was identified when the stent lumen distance was greater than the sum of strut thickness plus abluminal polymer thickness, according to each stent manufacturer’s specifications, plus a compensation factor of 20 μm to correct for strut blooming, and was considered significant if the stent lumen distance was >200 μm. Thrombus was defined as intraluminal mass ≥200 μm, with no direct continuity with the surface of the vessel wall or a highly backscattered luminal protrusion in continuity with the vessel wall and resulting in signal-free shadowing. Struts were classified as uncovered if any part of the strut was visibly exposed to the lumen or were classified as covered if a layer of tissue was visible over all the reflecting surfaces. Cross-sections with uncovered struts are defined if ≥1 stent strut is uncovered or malapposed on the cross-section, and cross-sections with an uncovered strut ratio >0.3 is defined when the ratio of uncovered struts to total stent struts per cross-section is >0.3. The thickness of neointimal hyperplasia was measured from the marker of each visible strut to the endoluminal edge of the tissue coverage, after a straight line connecting the strut marker with the center of gravity of the vessel: in case of no definite neointima over the stent strut, it was defined as an uncovered strut. The stent and lumen areas were measured by manual trace, and the percentage of the neointimal hyperplasia area was calculated as: neointimal hyperplasia area (%) = ([stent area – lumen area]/stent area) × 100. OCT image analysis has been performed by an external laboratory.
The primary end point of the study was the prevalence of uncovered struts evaluated by OCT analysis at 6 months follow-up. Additional end points were the prevalence of cross-sections with at least 1 uncovered strut and the prevalence of cross-sections with uncovered strut ratio >0.3; a cross-section with uncovered strut ratio >0.3 was defined when the ratio of uncovered struts to total stent struts per cross-section was >0.3. A comparison between the experimental group (DES in BMS restenosis) and the control group (DES in native coronary lesions) has been first carried out. Second, in the group with DES in BMS restenosis, segments with overlap of DES and BMS struts and segments with a single layer of DES struts have been compared.
Distributions of continuous variables were tested by the D’Agostino-Pearson test. Normally distributed variables were presented as mean ± SD, whereas non-normally distributed variables were presented as median (twenty-fifth to seventy-fifth percentile). Comparisons were performed with the Student’s t test or the Mann-Whitney test for the normally or non-normally distributed variables, respectively. The chi-square test was used for categorical binary variables. Significance threshold was set at p <0.05 (2 sided). The GraphPad Prism 4 software (GraphPad, La Jolla, California) was used for the analyses.
Results
Thirty-six patients (12 with BMS restenosis and 24 with atherosclerotic de novo lesions) were included in the study. Four withdrew their consent after DES implantation (1 with BMS restenosis and 3 with de novo lesions) and did not undergo angiography with OCT assessment at 6 months follow-up. A total of 32 patients completed the study: 11 subjects with DES implantation to treat BMS restenosis were labeled as group A, whereas the remaining 21 patients who received a DES to treat de novo lesions were labeled as group B. To compare overlapping and nonoverlapping struts, group A struts were further divided in group A1 (overlapped DES/BMS struts) and group A2 (DES struts protruding outside the BMS edges).
Clinical features and angiographic findings of patients are summarized in Table 1 and show no differences between the 2 groups in terms of age, gender, and incidence of cardiovascular risk factors. Left anterior descending was the most frequently treated coronary artery in both groups of patients. In group A vessel size, DES diameter and DES length were greater. At the OCT strut analysis ( Table 2 ), a total of 85,773 struts were evaluated (17,891 in group A and 67,882 in group B): the percentage of uncovered stent struts was significantly lower in group A compared with group B (2.6% vs 4.8%; p <0.0001). Consistently, the percentage of cross-sections with at least 1 uncovered strut was lower in group A (13.5% vs 21.8%; p <0.0001) and the percentage of cross-sections with uncovered struts ratio >0.3 (3.6% vs 7.9%; p <0.0001). Stent struts in group A were more frequently malapposed (2.6% vs 2%; p <0.0001). Stent area and lumen area were higher in group A, whereas no significant differences were detected regarding the neointima thickness diameter and neointima area. Comparison between groups A1 and A2 ( Table 3 ) revealed that DES struts protruding outside the BMS edges (A2) were more often uncovered (5.0% vs 1.9%; p <0.0001) and malapposed (4.1% vs 2.1%; p <0.0001) compared with overlapped struts (A1).
| Variable | Group A (N = 11) | Group B (N = 21) | P value |
|---|---|---|---|
| Age (years) | 65.4 ± 7.9 | 66.4 ± 9.3 | NS |
| Men | 10 (91%) | 15 (71%) | NS |
| Hypertension | 5 (45%) | 13 (62%) | NS |
| Diabetes mellitus | 2 (18%) | 6 (28%) | NS |
| Hyperlipidemia | 8 (73%) | 16 (76%) | NS |
| Smoking | 3 (27%) | 10 (48%) | NS |
| Family history of CAD | 5 (45%) | 9 (43%) | NS |
| Target coronary artery | |||
| Left anterior descending | 6 (55%) | 11 (52%) | |
| Circumflex | 0 (0%) | 5 (24%) | |
| Right | 5 (45%) | 5 (24%) | |
| Bifurcating lesion | 1 (9%) | 3 (14%) | NS |
| Mehran Class | 2.6 ± 0.9 | – | |
| Stent diameter (mm) | 3.4 ± 0.4 | 3.0 ± 0.3 | 0.03 |
| Multiple stent | 5 (45%) | 9 (43%) | NS |
| Stent length (mm) | 31.1 ± 14.5 | 22.2 ± 6.9 | 0.02 |
| Max pressure (atm) | 18.2 ± 1.4 | 18.8 ± 1.2 | NS |
| Post-intervention quantitative coronary angiography data | |||
| Mean reference vessel diameter (mm) | 3.5 ± 0.5 | 2.8 ± 0.4 | < 0.001 |
| Minimal lesion diameter (mm) | 2.7 ± 0.3 | 2.7 ± 0.4 | NS |
| Diameter stenosis (%) | 25.0 ± 8.7 | 10.0 ± 8.6 | NS |
| 6-month follow-up quantitative coronary angiography data | |||
| Mean reference vessel diameter (mm) | 3.6 ± 0.4 | 2.7 ± 0.4 | < 0.001 |
| Minimal lesion diameter (mm) | 2.5 ± 0.4 | 2.5 ± 0.3 | NS |
| Diameter stenosis (%) | 23.3 ± 12.0 | 8.9 ± 8.0 | < 0.01 |
| Late loss (mm) | 0.4 ± 0.2 | 0.2 ± 0.3 | 0.02 |
| Variable | Group A | Group B | P value |
|---|---|---|---|
| Total struts N° | 17891 | 67882 | |
| Uncovered struts | 474 (2.6%) | 3261 (4.8%) | < 0.0001 |
| Malapposed struts | 465 (2.6%) | 1363 (2%) | < 0.0001 |
| Uncovered and malapposed | 152 (0.8%) | 630 (0.9%) | NS |
| Cross sections | 1682 (19%) | 7315 (81%) | |
| Cross sections with uncovered struts | 227 (13.5%) | 1599 (21.8%) | <0.0001 |
| Cross section with uncovered strut ratio > 0.3 | 60 (3.6%) | 578 (7.9%) | <0.0001 |
| Neointima hyperplasia | |||
| Min thickness diameter (μm) | 10 [10-20] | 10 [10-30] | NS |
| Max thickness diameter (μm) | 220 [130-320] | 220 [160-290] | NS |
| Lumen area (mm 2 ) | 7.2 [6.1-9.1] | 7.1 [6.1-8.0] | < 0.001 |
| Stent area (mm 2 ) | 8.5 [7.2-9.8] | 8.0 [7.0-9.0] | < 0.0001 |
| Neointima area (mm 2 ) | 0.9 [0.5-1.6] | 0.9 [0.5-1.2] | NS |
| Neointima area (%) | 10.5 [6.1-19.3] | 10.1 [7.0-15.3] | NS |
| Variable | Group A1 | Group A2 | Group B |
|---|---|---|---|
| Total Struts N° | 13420 | 4471 | 67882 |
| Uncovered struts | 252 (1.9%) | 222 (5.0%)*** | 3261 (4.8%)*** |
| Malapposed struts | 282 (2.1%) | 183 (4.1%)*** | 1363 (2.0%) |
| Uncovered and malapposed | 71 (0.5%) | 81 (1.8%)*** | 630 (0.9%)*** |
| Covered by thrombosis | 93 (0.7%) | 18 (0.4%)* | 314 (0.5%)** |
| Cross sections N° | 1232 | 450 | 7315 |
| Cross sections with uncovered struts | 138 (11.2%) | 92 (20.4%)*** | 1599 (21.8%)*** |
| Cross section with uncovered strut ratio > 0.3 | 26 (2.1%) | 31 (6.9%)*** | 578 (7.9%)*** |
| Minimal thickness diameter (μm) | 10 [10-20] | 10 [10-55]* | 10 [10-30]* |
| Maximal thickness diameter (μm) | 220 [135-300] | 250 [110-437] | 220 [160-290] |
| Lumen area (mm 2 ) | 7.1 [6.0- 8.9] | 7.6 [6.1-10.7]* | 7.1 [6.1-8.0]* |
| Stent area (mm 2 ) | 8.1 [7.1-9.5] | 9.3 [7.7-11.8]*** | 8.0 [7.0-9.0]* |
| Neointima area (mm 2 ) | 0.81 [0.48-1.32] | 1.21 [0.43-2.64]* | 0.9 [0.5-1.2] |
| Neointima area (%) | 9.78 [6.2-16.8] | 12.2 [5.0-27.8] | 10.1 [7.0-15.3] |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
