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Clinical characteristics of stent fracture after sirolimus-eluting stent implantation
International Journal of Cardiology 131 (2009) 212 – 216 www.elsevier.com/locate/ijcard
Clinical characteristics of stent fracture after sirolimus-eluting stent implantation ☆ Tae-Hyun Yang, Doo-Il Kim ⁎, Seong-Gill Park, Jeong-Sook Seo, Hwan-Jin Cho, Sang-Hoon Seol, Seong-Man Kim, Dae-Kyeong Kim, Dong-Soo Kim Division of Cardiology, Department of Medicine, Inje University, Paik Hospital, Busan, Republic of Korea Received 7 February 2007; received in revised form 7 August 2007; accepted 20 October 2007 Available online 1 February 2008
Abstract Background: Despite several case reports of sirolimus-eluting stent (SES) fracture and concern regarding restenosis after successful SES implantation, the clinical characteristics of this problem are not well known. Methods: Clinical records and angiographic films of patients who received follow-up coronary angiography between February 2005 and October 2006 were retrospectively analyzed. Results: Among the 686 SES implanted in 479 patients, 27 fractures were found in 22 (3.2%) stents in 18 patients. All stent fractures occurred in long stented segments, i.e. ≥ 28 mm (range, 28 mm to 83 mm). Of the 22 fractured stents, sixteen (72.7%) were identified in the right coronary artery (RCA) and fifteen (68.2%) were found to have a fracture site within 10 mm from areas with increased rigidity due to metal overlap. The significant multivariate predictors of stent fracture were the stented length (Odds ratio 1.06; 95% confidence interval 1.04–1.09; p = 0.001) and the RCA location (Odds ratio 4.44; 95% confidence interval 1.66–11.86; p = 0.003). The binary restenosis rate was 22.7% and target lesion revascularization was performed in two (9.1%) fractured stents. Conclusions: SES fracture was associated with a long stented segment, RCA location and metal overlap. Stent fracture may be another potential risk factor for restenosis after successful SES implantation. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Sirolimus; Stent; Fracture
1. Introduction Although drug-eluting stents (DES), which have the capacity to reduce neointimal hyperplasia by the local delivery of anti-proliferative agents, are a very effective solution to the problem of restenosis [1,2], restenosis remains a clinical problem. Among the currently available drug-eluting stents, the sirolimus-eluting stent (SES) appears to be superior to the paclitaxel-eluting stent (PES) with ☆
This work was supported by the 2005 Inje University research grant. ⁎ Corresponding author. Department of Medicine, Inje University College of Medicine, Busan Paik Hospital, 633-165 Gaegeum-dong, Busanjin-gu, Busan, 614-735, Republic of Korea. Tel.: +82 51 890 6270; fax: +82 51 892 0273. E-mail address: [email protected] (D.-I. Kim). 0167-5273/$ - see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2007.10.059
regard to angiographic restenosis and target vessel revascularization [3]. Recently, several cases of stent fracture after SES implantation have been reported [4–8]. There is growing concern that stent fracture may be another cause of restenosis after successful SES implantation. However, its clinical characteristics, implications and management are not well known. 2. Materials and methods 2.1. Study population We retrospectively analyzed the clinical records and angiographic films of a consecutive series of 479 patients who received follow-up coronary angiography between
T.-H. Yang et al. / International Journal of Cardiology 131 (2009) 212–216 Table 1 Baseline clinical characteristics
213
including cilostazol (200 mg/day for at least six months) was used in some patients at the operator's discretion.
Patients (n = 479)
Fracture (n = 18) No fracture (n = 461) p
Male, n (%) Age (year) Diagnosis, n (%) Stable angina Unstable angina Acute myocardial infarction Follow-up duration (month)
11 (61.1) 63.0 ± 8.2
295 (64.0) 61.3 ± 9.9
0.81 0.41
5 (27.8) 6 (33.3) 7 (38.9)
175 (38.0) 148 (32.1) 138 (29.9)
0.46 1.0 0.44
7.4 ± 3.0
7.8 ± 3.4
0.61
February 2005 and October 2006 at our institution. A total of 686 SES (Cypher stent, Cordis Corp, Johnson & Johnson Company, Warren, New Jersey, USA) had been implanted for the treatment of a coronary artery diameter reduction of N 50% despite balloon angioplasty. A stent fracture was defined by a definitive fluoroscopic image of complete separation of the stent segments and/or the absence of a stent strut on at least one slice of an intravascular ultrasound (IVUS) image, which was absent at the time of the index procedure. 2.2. Coronary stent procedure The lesions were treated using standard interventional techniques. Balloon predilation was performed as per our standard protocol before stent placement. The final interventional strategy and the use of a post stenting additional balloon were left entirely to the operators' discretion. The anti-platelet regimen consisted of life-long aspirin (100– 200 mg/day) and clopidogrel (300 mg loading dose, 75 mg daily for at least six months). A triple anti-platelet regimen
2.3. Follow-up Follow-up coronary angiography was routinely planned 6 to 9 months after the index procedure unless it was clinically necessary at an earlier time. Follow-up angiograms were compared side by side with angiograms at the index procedure by two independent interventional cardiologists (T.H.Y, and D.I.K). Binary restenosis at follow-up was defined by a diameter stenosis of ≥ 50% within the stent or a gap between the stent strut formed by a stent fracture. The pre-procedure vessel angulation, where a stent fracture occurred, was measured in a pre-procedure non-foreshortened view at end diastolic frames as the angle formed by the centerline through the lumen proximal to the fracture site and opposite to a second centerline in the straight portion of the artery distal to the fracture site [9]. The vessel angulation was classified as minor (b 45°), moderate (45°–90°) and extreme (N 90°). An IVUS was routinely recommended when a stent fracture was found at follow-up angiography. However, all stent fractures were not verified by IVUS because of several reasons such as economic problem, technical difficulties etc. 2.4. Statistics Continuous variables are presented as means ± SD. Categorical variables are presented as numbers and frequencies. Comparisons were performed with the Student t-test and the Chi-square or Fisher's exact test. The multivariate logistic regression analysis was used to identify independent
Table 2 Characteristics related with lesion and procedure Stents (n = 686) Target vessel, n (%) Left anterior descending artery Left circumflex artery Right coronary artery Left main coronary artery Reference vessel diameter (mm) Pre minimal luminal diameter (mm) Diameter stenosis (%) Post minimal luminal diameter (mm) Acute gain (mm) Pre-procedure vessel angulation, n (%) Minor (b45°) Moderate (45°–90°) Extreme (N90°). Stent diameter (mm) Stented length (mm) Maximal inflation pressure (atm) Maximal balloon diameter/stent diameter ratio Metal overlap, n (%) a Bifurcation stenting, n (%) b a b
Bifurcation stenting is included. Bifurcation lesion treated with two stents.
Fracture (n = 22)
No fracture (n = 664)
p
3 (13.6) 3 (13.6) 16 (72.7) 0 (0) 3.02 ± 0.30 0.97 ± 0.77 67.6 ± 26.6 2.89 ± 0.30 1.92 ± 0.83
293 (44.1) 121 (18.2) 222 (33.4) 28 (4.2) 2.92 ± 0.50 0.98 ± 0.54 66.7 ± 16.8 2.85 ± 0.49 1.86 ± 0.58
b0.01 0.78 b0.01 1.0 0.37 0.91 0.80 0.68 0.65
7 (31.8) 8 (36.4) 7 (31.8) 2.97 ± 0.30 55.4 ± 18.8 14.7 ± 2.7 1.05 ± 0.04 15 (68.2) 2 (9.1)
NA NA NA 2.99 ± 0.35 34.9 ± 15.6 13.9 ± 3.6 1.05 ± 0.02 268 (40.4) 30 (4.5)
NA NA NA 0.74 b0.01 0.33 0.43 0.01 0.27
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Table 3 Follow-up results Stents (n = 686)
Fracture (n = 22) No fracture (n = 664) p
Follow-up minimal luminal diameter (mm) Late loss (mm) Binary restenosis, n (%) Target lesion revascularization, n (%)
2.10 ± 0.89
2.44 ± 0.72
0.08
0.79 ± 0.96 5 (22.7) 2 (9.1) a
0.39 ± 0.86 62 (9.3) 29 (4.4)
0.07 0.05 0.26
a
Used method was percutaneous optimal balloon angioplasty in all cases.
predictors of a stent fracture. A p value of b0.05 was considered to indicate statistical significance. All calculations were performed using SPSS 13 (SPSS Inc. Chicago, IL, USA). 3. Results A total of 675 patients had undergone SES implantation during the period when 479 patients included in this study had received SES implantation. So, the rate of follow-up coronary angiography was 71%. Stent fracture was observed in 18 patients and 27 stent fractures were found in 22 (3.2%) stents out of 686 SES used. Five stents had two fractures in one stent. All fractured stents were verified by coronary angiography, while 16 fractured stents were documented with both IVUS and coronary angiography. Overall, the baseline clinical characteristics were similar in comparisons between patients with and without a stent fracture. The clinical diagnoses of patients with a stent fracture were stable angina (27.8%), unstable angina (33.3%) and acute myocardial infarction (38.9%) (Table 1). All stent fractures occurred at long stented segments, i.e. ≥ 28 mm and the longest stented segment was 83 mm. In contrast, only 66.1% of stents in the group without stent fractures was implanted in stented segments above 28 mm. The group with stent fractures had longer stented segments compared with the group without stent
fractures (55.4 ± 18.8 vs. 34.9 ±15.6; p b 0.01). Of the 22 fractured stents, 16 (72.7%) were noted at the right coronary artery (RCA) and three each (13.6%) at the left anterior descending coronary artery (LAD) and the left circumflex artery (LCX). The RCA location was more common in the group with stent fractures compared with the group without stent fractures (72.7% vs. 33.4%; p b 0.01). Furthermore, fifteen stents (68.2%) were found to have fracture sites within 10 mm from areas of metal overlap where rigidity would be increased compared to the areas covered by a single stent strut. The mean length of the metal overlap was 2.82 mm. Bifurcation stenting was performed at two of the fracture sites using kissing stent or provisional T stent technique. The group with stent fractures had more frequently metal overlap compared with the group without stent fractures (68.2% vs. 40.4%; p = 0.01). Sixteen fractures in 15 (68.2%) stents developed where moderate or extreme angulation was present (Table 2). However, the maximum inflation pressure and balloon diameter/stent ratio were not different in comparisons between the two groups. The significant multivariate predictors of stent fracture were the stented length (Odds ratio 1.06; 95% confidence interval 1.04–1.09; p = 0.001) and the RCA location (Odds ratio 4.44; 95% confidence interval 1.66–11.86; p = 0.003). The binary restenosis rate was higher in the group with stent fractures compared with the group without stent fractures, however, this difference had borderline statistical significance (22.7% vs. 9.3%; p = 0.05) (Table 3). The pattern of restenosis was focal at the site of the stent fracture and neointimal growth did not extend into the stent body. Interestingly, one patient who developed two stent fractures had an in-stent restenosis where the stent strut was intact (Figs. 1 and 2). The target lesion revascularization rate was not different in comparison between the two groups (9.1% vs. 4.4%; p = 0.26). Of the five patients with binary restenosis that was related to a stent fracture, three patients had angina symptom. Two patients underwent balloon angioplasty for
Fig. 1. Right coronary angiography showing (A) preintervention stenosis, (B) final result after stent implantation and (C) follow-up angiography. Diffuse right coronary artery stenosis was consecutively stented with two 3.0 × 33 mm sirolimus-eluting stents and a 3.5 × 18 mm stent was implanted to treat proximal stent edge dissection. Two complete stent fractures with minimal luminal narrowing at the proximal and mid right coronary artery are shown (arrow). Paradoxically, in-stent restenosis is shown where stent strut is intact (arrow head). Solid lines denote stent strut shadow.
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215
Fig. 2. Intravascular ultrasound image of the right coronary artery in same patient described in Fig. 1. B and E denote stent gap without a visible strut corresponding to the angiographic finding. A and F denote the overlapped segment with double layers of stent strut.
the restenotic lesion (Fig. 3). However, the remaining three patients are being followed with no additional revascularization treatment. Stent thrombosis related to a stent fracture was not observed during the study period. 4. Discussion The results of this study showed that the incidence of a stent fracture after SES implantation was 3.2%. In addition, we found that stent fractures were associated with long stented segments, RCA location and metal overlap. Furthermore, we found that the binary restenosis rate at fracture sites might be higher than at non-fracture sites. Coronary bare metal stent fractures in venous bypass grafts have been reported [10–12]. In a graft, the mechanical stresses can be very high, depending on the curvature of the graft, the presence of perigraft fibrosis and the intrathoracic space available. It has been reported that a stent fracture after SES implantation occurred in 2.9% of patients who underwent follow-up coronary angiography [13]. Similar to our results, a long stented segment including overlapping implantation and more than a 40° angulated implantation predisposed the stent
to fracture. More recently, Aoki et al. [14] reported that stent fractures were observed in 2.6% lesions, they reported an association with saphenous vein graft location, implanted stent length and RCA location. To our knowledge, fracture of the Bx-Velocity stent® (Cordis Corp, Johnson & Johnson Company) which is a bare metal stent of SES has not been described before. However, no data have indicated whether the occurrence of a stent fracture would be affected by sirolimus blended with synthetic polymers. Much more neointimal hyperplasia after Bx-Velocity stent® implantation compared to the SES may be one possible cause of this phenomenon. In fact, the exact mechanism of stent fracture is unknown. Multiple mechanical factors such as long stented segments, increased rigidity and pre-procedure vessel angulation might interact to disrupt the stent strut. Similar to the observations in several case reports [4–7], stent fractures occurred only in long stented segments, i.e. ≥28 mm and stented length was the most powerful predictor of stent fracture in the present study. The fact that stent fracture is strongly associated with long stented segments is also evident in the study by Aoki et al. [14]. The majority of stent fractures occurred within 10 mm from areas of increased rigidity caused by strut overlap that may
Fig. 3. Right coronary angiography showing (A) preintervention stenosis, (B) final result after stent implantation and (C) follow-up angiography. Diffuse right coronary artery stenosis was consecutively stented with two 3.5 × 33 mm sirolimus-eluting stents. One complete stent fracture with nearly total in-stent restenosis at the mid right coronary artery is shown (arrow). This restenotic lesion was treated by balloon angioplasty. Solid lines denote strut shadow.
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have acted as a fulcrum for metal deformation due to vessel movement. In addition, 16 fractures in 15 (68.2%) stents developed where moderate or extreme angulation was present. Other important possible mechanisms such as vessel movement and repetitive kinking of the stent during the cardiac cycle may also be implicated in stent fractures. Considering that RCA has more vessel movement and curvature than LAD or LCX, the high occurrence rate of a stent fracture in RCA may be partially explained by these factors. Interestingly, one patient developed four stent fractures in a very long tortuous RCA implanted with four overlapping stents. These findings support the hypothesis that the implantation of multiple overlapping stents significantly increases the axial stiffness of the stented segment and longer stents covering longer lesions are subject to higher radial forces, especially when placed in angulated lesions. Although previous case reports suggested that implantation of long stents concomitantly with postdilatation with larger balloon at high pressures was related to a stent fracture [4,11], post-dilatation balloon size and inflation pressure were not related to stent fracture in the present study. It was interesting that no stent fracture was found in 124 patients who had underwent stent implantation with 158 PES (Taxus stent, Boston Scientific Corp, Natick, Minnesota, USA) and received follow-up angiography during the same period at our institution. SES is a closed cell structure compared to the open cell structure of PES. The radio-opacity of the stent struts is higher in SES compared to PES. These structural differences may be transformed into different appearance regarding stent fracture. The most interesting finding of this study was the clinical implications of the stent fracture. Consistent with previous studies [13,14], our data demonstrated that the binary restenosis rate was higher in the group with stent fractures than in the group without stent fractures, although this difference had borderline statistical significance. Furthermore, late loss was insignificantly higher in the group with stent fractures than in the group without stent fractures. Local mechanical irritation of the vessel can occur from fractured stent struts, which may result in inflammation and neointimal hyperplasia. Another issue to resolve is the timing of stent fracture, however, the exact timing of stent fracture is currently unknown. In addition, the length of time that a vessel is exposed to a fractured stent struts may be important to the development of additional problems. Seeing that significant restenosis had not developed over the half of the fracture sites, it may be presumed that stent strut was fractured long enough after the intervention so that the sirolimus effect was not compromised [5]. However, an acute/ subacute fracture may be another possible scenario. Additional study with a larger population and longer follow-up duration may be needed to determine more accurate timing of a stent fracture and the clinical implications after SES implanation. There are some limitations of this study that leave our understanding of the mechanisms and clinical implications of stent fracture incomplete. First, this study was based on conventional angiographic investigations performed in patents
who received follow-up coronary angiography. Because follow-up angiographic data was not available in every patient who underwent SES implantation, an accurate frequency of SES fracture could not be obtained. In addition, new technology such as the Stentboost, which can show enhanced stent strut shadows, may increase the detection rate of stent fractures. Therefore, our study results may have underestimated the frequency of stent fractures. Second, follow-up angiography was conducted at an average of 7 months. The restenosis rate at the fracture site over a longer period of follow-up may be different. Finally, the study design was a retrospective analysis of angiographic and clinical data conducted at a single center. These factors may have added unintended bias to the outcome. In conclusion, this study showed that SES fracture was associated with a long stented segment, RCA location and metal overlap. Stent fracture may be another potential risk factor for restenosis after successful SES implantation. References [1] Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003;349:1315–23. [2] Stone GW, Ellis SG, Cox DA, et al. A polymer-based, paclitaxeleluting stent in patients with coronary artery disease. N Engl J Med 2004;350:221–31. [3] Kastrati A, Dibra A, Eberle S, et al. Sirolimus-eluting stents vs paclitaxel-eluting stents in patients with coronary artery disease. JAMA 2005;294:819–25. [4] Sianos G, Hofma S, Ligthart JM, et al. Stent fracture and restenosis in the drug-eluting stent era. Catheter Cardiovasc Interv 2004;61:111–6. [5] Halkin A, Carlier S, Leon MB. Late incomplete lesion coverage following Cypher stent deployment for diffuse right coronary artery stenosis. Heart 2004;90:e45. [6] Shite J, Matsumoto D, Yokoyama M. Sirolimus-eluting stent fracture with thrombus, visualization by optical coherence tomography. Eur Heart J 2005;24:24. [7] Min PK, Yoon YW, Kwon HK. Delayed strut fracture of sirolimus-eluting stent: a significant problem or an occasional observation? Int J Cardiol 2006;106:404–6. [8] Surmely JF, Kinoshita Y, Dash D, et al. Stent strut fracture-induced restenosis in a bifurcation lesion treated with the crush stenting technique. Circ J 2006;70:936–8. [9] Popma JJ, Gibson MC. Qualitative and quantitative angiography. In: Topol EF, editor. Textbook of interventional cardiology. 4th ed. Philadelphia: WB Saunders; 2003. p. 827–46. [10] Chowdhury PS, Ramos RG. Images in clinical medicine: coronarystent fracture. N Engl J Med 2002;347:581. [11] Brilakis ES, Maniu C, Wahl M, Barsness G. Unstable angina due to stent fracture. J Invasive Cardiol 2004;16:545. [12] Dorsch MF, Seidelin PH, Blackman DJ. Stent fracture and collapse in a saphenous vein graft causing occlusive restenosis. J Invasive Cardiol 2006;18:e137–9. [13] Kim JS, Yoon YW, Hong BK, et al. Delayed stent fracture after successful sirolimus – eluting stent (Cypher®) implantation. Korean Circ J 2006;36:443–9. [14] Aoki J, Nakazawa G, Tanabe K, et al. Incidence and clinical impact of coronary stent fracture after sirolimus-eluting stent implantation. Catheter Cardiovasc Interv 2007;69:380–6.
Clinical characteristics of stent fracture after sirolimus-eluting stent implantation ☆ Tae-Hyun Yang, Doo-Il Kim ⁎, Seong-Gill Park, Jeong-Sook Seo, Hwan-Jin Cho, Sang-Hoon Seol, Seong-Man Kim, Dae-Kyeong Kim, Dong-Soo Kim Division of Cardiology, Department of Medicine, Inje University, Paik Hospital, Busan, Republic of Korea Received 7 February 2007; received in revised form 7 August 2007; accepted 20 October 2007 Available online 1 February 2008
Abstract Background: Despite several case reports of sirolimus-eluting stent (SES) fracture and concern regarding restenosis after successful SES implantation, the clinical characteristics of this problem are not well known. Methods: Clinical records and angiographic films of patients who received follow-up coronary angiography between February 2005 and October 2006 were retrospectively analyzed. Results: Among the 686 SES implanted in 479 patients, 27 fractures were found in 22 (3.2%) stents in 18 patients. All stent fractures occurred in long stented segments, i.e. ≥ 28 mm (range, 28 mm to 83 mm). Of the 22 fractured stents, sixteen (72.7%) were identified in the right coronary artery (RCA) and fifteen (68.2%) were found to have a fracture site within 10 mm from areas with increased rigidity due to metal overlap. The significant multivariate predictors of stent fracture were the stented length (Odds ratio 1.06; 95% confidence interval 1.04–1.09; p = 0.001) and the RCA location (Odds ratio 4.44; 95% confidence interval 1.66–11.86; p = 0.003). The binary restenosis rate was 22.7% and target lesion revascularization was performed in two (9.1%) fractured stents. Conclusions: SES fracture was associated with a long stented segment, RCA location and metal overlap. Stent fracture may be another potential risk factor for restenosis after successful SES implantation. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Sirolimus; Stent; Fracture
1. Introduction Although drug-eluting stents (DES), which have the capacity to reduce neointimal hyperplasia by the local delivery of anti-proliferative agents, are a very effective solution to the problem of restenosis [1,2], restenosis remains a clinical problem. Among the currently available drug-eluting stents, the sirolimus-eluting stent (SES) appears to be superior to the paclitaxel-eluting stent (PES) with ☆
This work was supported by the 2005 Inje University research grant. ⁎ Corresponding author. Department of Medicine, Inje University College of Medicine, Busan Paik Hospital, 633-165 Gaegeum-dong, Busanjin-gu, Busan, 614-735, Republic of Korea. Tel.: +82 51 890 6270; fax: +82 51 892 0273. E-mail address: [email protected] (D.-I. Kim). 0167-5273/$ - see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2007.10.059
regard to angiographic restenosis and target vessel revascularization [3]. Recently, several cases of stent fracture after SES implantation have been reported [4–8]. There is growing concern that stent fracture may be another cause of restenosis after successful SES implantation. However, its clinical characteristics, implications and management are not well known. 2. Materials and methods 2.1. Study population We retrospectively analyzed the clinical records and angiographic films of a consecutive series of 479 patients who received follow-up coronary angiography between
T.-H. Yang et al. / International Journal of Cardiology 131 (2009) 212–216 Table 1 Baseline clinical characteristics
213
including cilostazol (200 mg/day for at least six months) was used in some patients at the operator's discretion.
Patients (n = 479)
Fracture (n = 18) No fracture (n = 461) p
Male, n (%) Age (year) Diagnosis, n (%) Stable angina Unstable angina Acute myocardial infarction Follow-up duration (month)
11 (61.1) 63.0 ± 8.2
295 (64.0) 61.3 ± 9.9
0.81 0.41
5 (27.8) 6 (33.3) 7 (38.9)
175 (38.0) 148 (32.1) 138 (29.9)
0.46 1.0 0.44
7.4 ± 3.0
7.8 ± 3.4
0.61
February 2005 and October 2006 at our institution. A total of 686 SES (Cypher stent, Cordis Corp, Johnson & Johnson Company, Warren, New Jersey, USA) had been implanted for the treatment of a coronary artery diameter reduction of N 50% despite balloon angioplasty. A stent fracture was defined by a definitive fluoroscopic image of complete separation of the stent segments and/or the absence of a stent strut on at least one slice of an intravascular ultrasound (IVUS) image, which was absent at the time of the index procedure. 2.2. Coronary stent procedure The lesions were treated using standard interventional techniques. Balloon predilation was performed as per our standard protocol before stent placement. The final interventional strategy and the use of a post stenting additional balloon were left entirely to the operators' discretion. The anti-platelet regimen consisted of life-long aspirin (100– 200 mg/day) and clopidogrel (300 mg loading dose, 75 mg daily for at least six months). A triple anti-platelet regimen
2.3. Follow-up Follow-up coronary angiography was routinely planned 6 to 9 months after the index procedure unless it was clinically necessary at an earlier time. Follow-up angiograms were compared side by side with angiograms at the index procedure by two independent interventional cardiologists (T.H.Y, and D.I.K). Binary restenosis at follow-up was defined by a diameter stenosis of ≥ 50% within the stent or a gap between the stent strut formed by a stent fracture. The pre-procedure vessel angulation, where a stent fracture occurred, was measured in a pre-procedure non-foreshortened view at end diastolic frames as the angle formed by the centerline through the lumen proximal to the fracture site and opposite to a second centerline in the straight portion of the artery distal to the fracture site [9]. The vessel angulation was classified as minor (b 45°), moderate (45°–90°) and extreme (N 90°). An IVUS was routinely recommended when a stent fracture was found at follow-up angiography. However, all stent fractures were not verified by IVUS because of several reasons such as economic problem, technical difficulties etc. 2.4. Statistics Continuous variables are presented as means ± SD. Categorical variables are presented as numbers and frequencies. Comparisons were performed with the Student t-test and the Chi-square or Fisher's exact test. The multivariate logistic regression analysis was used to identify independent
Table 2 Characteristics related with lesion and procedure Stents (n = 686) Target vessel, n (%) Left anterior descending artery Left circumflex artery Right coronary artery Left main coronary artery Reference vessel diameter (mm) Pre minimal luminal diameter (mm) Diameter stenosis (%) Post minimal luminal diameter (mm) Acute gain (mm) Pre-procedure vessel angulation, n (%) Minor (b45°) Moderate (45°–90°) Extreme (N90°). Stent diameter (mm) Stented length (mm) Maximal inflation pressure (atm) Maximal balloon diameter/stent diameter ratio Metal overlap, n (%) a Bifurcation stenting, n (%) b a b
Bifurcation stenting is included. Bifurcation lesion treated with two stents.
Fracture (n = 22)
No fracture (n = 664)
p
3 (13.6) 3 (13.6) 16 (72.7) 0 (0) 3.02 ± 0.30 0.97 ± 0.77 67.6 ± 26.6 2.89 ± 0.30 1.92 ± 0.83
293 (44.1) 121 (18.2) 222 (33.4) 28 (4.2) 2.92 ± 0.50 0.98 ± 0.54 66.7 ± 16.8 2.85 ± 0.49 1.86 ± 0.58
b0.01 0.78 b0.01 1.0 0.37 0.91 0.80 0.68 0.65
7 (31.8) 8 (36.4) 7 (31.8) 2.97 ± 0.30 55.4 ± 18.8 14.7 ± 2.7 1.05 ± 0.04 15 (68.2) 2 (9.1)
NA NA NA 2.99 ± 0.35 34.9 ± 15.6 13.9 ± 3.6 1.05 ± 0.02 268 (40.4) 30 (4.5)
NA NA NA 0.74 b0.01 0.33 0.43 0.01 0.27
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Table 3 Follow-up results Stents (n = 686)
Fracture (n = 22) No fracture (n = 664) p
Follow-up minimal luminal diameter (mm) Late loss (mm) Binary restenosis, n (%) Target lesion revascularization, n (%)
2.10 ± 0.89
2.44 ± 0.72
0.08
0.79 ± 0.96 5 (22.7) 2 (9.1) a
0.39 ± 0.86 62 (9.3) 29 (4.4)
0.07 0.05 0.26
a
Used method was percutaneous optimal balloon angioplasty in all cases.
predictors of a stent fracture. A p value of b0.05 was considered to indicate statistical significance. All calculations were performed using SPSS 13 (SPSS Inc. Chicago, IL, USA). 3. Results A total of 675 patients had undergone SES implantation during the period when 479 patients included in this study had received SES implantation. So, the rate of follow-up coronary angiography was 71%. Stent fracture was observed in 18 patients and 27 stent fractures were found in 22 (3.2%) stents out of 686 SES used. Five stents had two fractures in one stent. All fractured stents were verified by coronary angiography, while 16 fractured stents were documented with both IVUS and coronary angiography. Overall, the baseline clinical characteristics were similar in comparisons between patients with and without a stent fracture. The clinical diagnoses of patients with a stent fracture were stable angina (27.8%), unstable angina (33.3%) and acute myocardial infarction (38.9%) (Table 1). All stent fractures occurred at long stented segments, i.e. ≥ 28 mm and the longest stented segment was 83 mm. In contrast, only 66.1% of stents in the group without stent fractures was implanted in stented segments above 28 mm. The group with stent fractures had longer stented segments compared with the group without stent
fractures (55.4 ± 18.8 vs. 34.9 ±15.6; p b 0.01). Of the 22 fractured stents, 16 (72.7%) were noted at the right coronary artery (RCA) and three each (13.6%) at the left anterior descending coronary artery (LAD) and the left circumflex artery (LCX). The RCA location was more common in the group with stent fractures compared with the group without stent fractures (72.7% vs. 33.4%; p b 0.01). Furthermore, fifteen stents (68.2%) were found to have fracture sites within 10 mm from areas of metal overlap where rigidity would be increased compared to the areas covered by a single stent strut. The mean length of the metal overlap was 2.82 mm. Bifurcation stenting was performed at two of the fracture sites using kissing stent or provisional T stent technique. The group with stent fractures had more frequently metal overlap compared with the group without stent fractures (68.2% vs. 40.4%; p = 0.01). Sixteen fractures in 15 (68.2%) stents developed where moderate or extreme angulation was present (Table 2). However, the maximum inflation pressure and balloon diameter/stent ratio were not different in comparisons between the two groups. The significant multivariate predictors of stent fracture were the stented length (Odds ratio 1.06; 95% confidence interval 1.04–1.09; p = 0.001) and the RCA location (Odds ratio 4.44; 95% confidence interval 1.66–11.86; p = 0.003). The binary restenosis rate was higher in the group with stent fractures compared with the group without stent fractures, however, this difference had borderline statistical significance (22.7% vs. 9.3%; p = 0.05) (Table 3). The pattern of restenosis was focal at the site of the stent fracture and neointimal growth did not extend into the stent body. Interestingly, one patient who developed two stent fractures had an in-stent restenosis where the stent strut was intact (Figs. 1 and 2). The target lesion revascularization rate was not different in comparison between the two groups (9.1% vs. 4.4%; p = 0.26). Of the five patients with binary restenosis that was related to a stent fracture, three patients had angina symptom. Two patients underwent balloon angioplasty for
Fig. 1. Right coronary angiography showing (A) preintervention stenosis, (B) final result after stent implantation and (C) follow-up angiography. Diffuse right coronary artery stenosis was consecutively stented with two 3.0 × 33 mm sirolimus-eluting stents and a 3.5 × 18 mm stent was implanted to treat proximal stent edge dissection. Two complete stent fractures with minimal luminal narrowing at the proximal and mid right coronary artery are shown (arrow). Paradoxically, in-stent restenosis is shown where stent strut is intact (arrow head). Solid lines denote stent strut shadow.
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Fig. 2. Intravascular ultrasound image of the right coronary artery in same patient described in Fig. 1. B and E denote stent gap without a visible strut corresponding to the angiographic finding. A and F denote the overlapped segment with double layers of stent strut.
the restenotic lesion (Fig. 3). However, the remaining three patients are being followed with no additional revascularization treatment. Stent thrombosis related to a stent fracture was not observed during the study period. 4. Discussion The results of this study showed that the incidence of a stent fracture after SES implantation was 3.2%. In addition, we found that stent fractures were associated with long stented segments, RCA location and metal overlap. Furthermore, we found that the binary restenosis rate at fracture sites might be higher than at non-fracture sites. Coronary bare metal stent fractures in venous bypass grafts have been reported [10–12]. In a graft, the mechanical stresses can be very high, depending on the curvature of the graft, the presence of perigraft fibrosis and the intrathoracic space available. It has been reported that a stent fracture after SES implantation occurred in 2.9% of patients who underwent follow-up coronary angiography [13]. Similar to our results, a long stented segment including overlapping implantation and more than a 40° angulated implantation predisposed the stent
to fracture. More recently, Aoki et al. [14] reported that stent fractures were observed in 2.6% lesions, they reported an association with saphenous vein graft location, implanted stent length and RCA location. To our knowledge, fracture of the Bx-Velocity stent® (Cordis Corp, Johnson & Johnson Company) which is a bare metal stent of SES has not been described before. However, no data have indicated whether the occurrence of a stent fracture would be affected by sirolimus blended with synthetic polymers. Much more neointimal hyperplasia after Bx-Velocity stent® implantation compared to the SES may be one possible cause of this phenomenon. In fact, the exact mechanism of stent fracture is unknown. Multiple mechanical factors such as long stented segments, increased rigidity and pre-procedure vessel angulation might interact to disrupt the stent strut. Similar to the observations in several case reports [4–7], stent fractures occurred only in long stented segments, i.e. ≥28 mm and stented length was the most powerful predictor of stent fracture in the present study. The fact that stent fracture is strongly associated with long stented segments is also evident in the study by Aoki et al. [14]. The majority of stent fractures occurred within 10 mm from areas of increased rigidity caused by strut overlap that may
Fig. 3. Right coronary angiography showing (A) preintervention stenosis, (B) final result after stent implantation and (C) follow-up angiography. Diffuse right coronary artery stenosis was consecutively stented with two 3.5 × 33 mm sirolimus-eluting stents. One complete stent fracture with nearly total in-stent restenosis at the mid right coronary artery is shown (arrow). This restenotic lesion was treated by balloon angioplasty. Solid lines denote strut shadow.
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have acted as a fulcrum for metal deformation due to vessel movement. In addition, 16 fractures in 15 (68.2%) stents developed where moderate or extreme angulation was present. Other important possible mechanisms such as vessel movement and repetitive kinking of the stent during the cardiac cycle may also be implicated in stent fractures. Considering that RCA has more vessel movement and curvature than LAD or LCX, the high occurrence rate of a stent fracture in RCA may be partially explained by these factors. Interestingly, one patient developed four stent fractures in a very long tortuous RCA implanted with four overlapping stents. These findings support the hypothesis that the implantation of multiple overlapping stents significantly increases the axial stiffness of the stented segment and longer stents covering longer lesions are subject to higher radial forces, especially when placed in angulated lesions. Although previous case reports suggested that implantation of long stents concomitantly with postdilatation with larger balloon at high pressures was related to a stent fracture [4,11], post-dilatation balloon size and inflation pressure were not related to stent fracture in the present study. It was interesting that no stent fracture was found in 124 patients who had underwent stent implantation with 158 PES (Taxus stent, Boston Scientific Corp, Natick, Minnesota, USA) and received follow-up angiography during the same period at our institution. SES is a closed cell structure compared to the open cell structure of PES. The radio-opacity of the stent struts is higher in SES compared to PES. These structural differences may be transformed into different appearance regarding stent fracture. The most interesting finding of this study was the clinical implications of the stent fracture. Consistent with previous studies [13,14], our data demonstrated that the binary restenosis rate was higher in the group with stent fractures than in the group without stent fractures, although this difference had borderline statistical significance. Furthermore, late loss was insignificantly higher in the group with stent fractures than in the group without stent fractures. Local mechanical irritation of the vessel can occur from fractured stent struts, which may result in inflammation and neointimal hyperplasia. Another issue to resolve is the timing of stent fracture, however, the exact timing of stent fracture is currently unknown. In addition, the length of time that a vessel is exposed to a fractured stent struts may be important to the development of additional problems. Seeing that significant restenosis had not developed over the half of the fracture sites, it may be presumed that stent strut was fractured long enough after the intervention so that the sirolimus effect was not compromised [5]. However, an acute/ subacute fracture may be another possible scenario. Additional study with a larger population and longer follow-up duration may be needed to determine more accurate timing of a stent fracture and the clinical implications after SES implanation. There are some limitations of this study that leave our understanding of the mechanisms and clinical implications of stent fracture incomplete. First, this study was based on conventional angiographic investigations performed in patents
who received follow-up coronary angiography. Because follow-up angiographic data was not available in every patient who underwent SES implantation, an accurate frequency of SES fracture could not be obtained. In addition, new technology such as the Stentboost, which can show enhanced stent strut shadows, may increase the detection rate of stent fractures. Therefore, our study results may have underestimated the frequency of stent fractures. Second, follow-up angiography was conducted at an average of 7 months. The restenosis rate at the fracture site over a longer period of follow-up may be different. Finally, the study design was a retrospective analysis of angiographic and clinical data conducted at a single center. These factors may have added unintended bias to the outcome. In conclusion, this study showed that SES fracture was associated with a long stented segment, RCA location and metal overlap. Stent fracture may be another potential risk factor for restenosis after successful SES implantation. References [1] Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003;349:1315–23. [2] Stone GW, Ellis SG, Cox DA, et al. A polymer-based, paclitaxeleluting stent in patients with coronary artery disease. N Engl J Med 2004;350:221–31. [3] Kastrati A, Dibra A, Eberle S, et al. Sirolimus-eluting stents vs paclitaxel-eluting stents in patients with coronary artery disease. JAMA 2005;294:819–25. [4] Sianos G, Hofma S, Ligthart JM, et al. Stent fracture and restenosis in the drug-eluting stent era. Catheter Cardiovasc Interv 2004;61:111–6. [5] Halkin A, Carlier S, Leon MB. Late incomplete lesion coverage following Cypher stent deployment for diffuse right coronary artery stenosis. Heart 2004;90:e45. [6] Shite J, Matsumoto D, Yokoyama M. Sirolimus-eluting stent fracture with thrombus, visualization by optical coherence tomography. Eur Heart J 2005;24:24. [7] Min PK, Yoon YW, Kwon HK. Delayed strut fracture of sirolimus-eluting stent: a significant problem or an occasional observation? Int J Cardiol 2006;106:404–6. [8] Surmely JF, Kinoshita Y, Dash D, et al. Stent strut fracture-induced restenosis in a bifurcation lesion treated with the crush stenting technique. Circ J 2006;70:936–8. [9] Popma JJ, Gibson MC. Qualitative and quantitative angiography. In: Topol EF, editor. Textbook of interventional cardiology. 4th ed. Philadelphia: WB Saunders; 2003. p. 827–46. [10] Chowdhury PS, Ramos RG. Images in clinical medicine: coronarystent fracture. N Engl J Med 2002;347:581. [11] Brilakis ES, Maniu C, Wahl M, Barsness G. Unstable angina due to stent fracture. J Invasive Cardiol 2004;16:545. [12] Dorsch MF, Seidelin PH, Blackman DJ. Stent fracture and collapse in a saphenous vein graft causing occlusive restenosis. J Invasive Cardiol 2006;18:e137–9. [13] Kim JS, Yoon YW, Hong BK, et al. Delayed stent fracture after successful sirolimus – eluting stent (Cypher®) implantation. Korean Circ J 2006;36:443–9. [14] Aoki J, Nakazawa G, Tanabe K, et al. Incidence and clinical impact of coronary stent fracture after sirolimus-eluting stent implantation. Catheter Cardiovasc Interv 2007;69:380–6.