Long-Term Clinical Outcome and Routine Angiographic Follow-up After Successful Recanalization of Complex Coronary True Chronic Total Occlusion With a Long Stent Length: A Single-Center Experience

Abstract: Objectives. To evaluate clinical and angiographic outcomes after successful recanalization of chronic total coronary occlusion (CTO) with implantation of a long total stent length (SL). Background. Routine follow-up angiogram (RFUA) data after successful recanalization of CTO with a long SL are lacking. Methods.  RFUAs were performed at 6 months after successful recanalization of 106 CTOs using drug-eluting stents (DESs) with a long SL (≥20 mm) in 102 consecutive patients. Results. Mean number of stents was 3.9 ± 1.8 and mean total SL was 78± 32 mm (range, 23-174 mm). Sirolimus-eluting stents (SESs) were used in 100 lesions. In-stent total reocclusion occurred in 2 cases (1 SES and 1 non-SES DES). Restenosis rate was 18% in the 100 SES subgroup (total SL, 79 ± 33 mm; range, 23-174 mm; mean number of stents, 3.9 ± 1.8); younger age and longer total SL were found to be independent predictors of restenosis (longer age: hazard ratio, 0.939; 95% confidence interval, 0.885-0.996; P=.035; longer total SL: hazard ratio, 1.017; 95% confidence interval, 1.00-1.03; P=.045). Restenosis type was diffuse in only 11% and 89% were successfully treated by repeat percutaneous coronary intervention. During a median follow-up of 2 years (interquartile range, 1-4.3 years), major cardiac events other than those angiographically driven at RFUA occurred in 2 patients. Conclusion. Angiographic restenosis rate remains acceptable in patients with complex CTO successfully treated by DES despite a long SL.

J INVASIVE CARDIOL 2013;25(7):323-329

Key words: chronic total occlusion, coronary occlusion, drug-eluting stent, restenosis

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Recanalization of true chronic total coronary occlusion (CTO), defined as a duration of occlusion >3 months and a thrombolysis in myocardial infarction (TIMI) flow grade 0, is considered to be the most challenging percutaneous coronary intervention (PCI). Although CTO can be identified in 15%-30% of all patients referred for coronary angiography,^1,2 and despite the progress made in techniques and technology during the past years, CTO-PCI attempt rates still remain relatively low.³ Operator reluctance to attempt CTO-PCI is due to the high complexity of the procedures, in particular the difficulties in crossing the occlusion with wire, and the fear of high restenosis rates.³ Indeed, high rates of restenosisand reocclusion have been documented in the past after balloon angioplasty and even after bare-metal stent (BMS) implantation for CTO lesions.^4,5 More recently, several studies have shown that CTO-PCI with drug-eluting stent (DES) implantation results in less restenosis when compared with BMS.⁶ However, there are few data reported in the literature on routine angiographic follow-up after successful PCI recanalization of true CTO using DESs. Routine follow-up angiography (RFUA) is, however, the only approach that allows the evaluation of actual restenosis rates since restenosis or even reocclusion can be totally silent after CTO-PCI.⁷ Several previous published studies have reported the results of systematic follow-up angiography after successful CTO-PCI with DESs,^8-21 but in small series of patients (sometimes less than 50) for many of them,^8-10,12-18 and often without evaluation of restenosis predictors^{8-11,14,17,18,21} or with a small number of stents implanted over a relatively short length.^{9-11,14-18,21} Since CTO vessels are often severely diffusely diseased, they often require the implantation of stents over a long length of arterial segment. The angiographic outcome of successful true CTO recanalization by PCI using a long stenting length that may increase the restenosis rate remains relatively unexplored. In the present study, we report routine 6-month angiographic follow-up in a large series of true complex CTOs successfully recanalized by PCI with the implantation of a long length of DESs and we provide a detailed analysis of restenosis predictors.

Methods

Study population and clinical definitions. From October 2008 to November 2011, PCIs were performed by a single operator (KI) in our institution for 164 true CTOs in 156 successive patients. Among these 164 CTO procedures, PCI was successful in 137 cases. CTO procedural angiographic success was defined as a final residual stenosis <30% with a post-PCI thrombolysis in myocardial infarction (TIMI) grade flow 3. Among these 137 successful CTO cases, a total of 129 were treated using DESs. Among these 129 CTO lesions, a total of 3 were treated with a short stent length (<20 mm) and 19 patients with 20 CTO lesions denied the RFUA at 6 months. Therefore, the final study population included 102 patients with 106 CTO lesions successfully treated using DESs with a stent length ≥20 mm and who all underwent RFUA at 6 months. Coronary CTOs were defined as TIMI grade 0 flow within the occluded segment with an occlusion duration >3 months estimated from clinical events, symptoms, or previous coronary angiogram. According to the definitions of CTO lesions given by the European CTO club²² and the findings of other previously published studies,^23,24 patients in whom there was no clinical evidence of the time the occlusion developed or no previous coronary angiogram but in whom angiographic findings were consistent with a CTO (no contrast staining and bridging collaterals) were also included. PCI was performed in all patients based on the presence of stress symptoms or silent ischemia with documented viable myocardium in the territory of the occluded artery by scintigraphy or cardiac magnetic resonance imaging. All patients gave written consent to be included in the study. 

Interventional procedure. All patients were given 300 mg of clopidogrel and 250 mg of aspirin the day before the procedure. Bolus intravenous injection of unfractionated heparin (5000-10000 U) with 250 mg aspirin was administrated at the beginning of the procedure and activated clotting time (ACT) was monitored every 30 minutes with additional boluses of unfractioned heparin if necessary to maintain permanently an ACT >300 seconds. All procedures were performed by one operator (KI) using transfemoral approach with antegrade 7 Fr or 8 Fr guiding catheters in most cases and using controlateral selective injection with 5 Fr to 6 Fr guiding catheter in every case where the distal bed of the occluded vessel was supplied by controlateral collaterals. Retrograde techniques were performed using 6 Fr or 7 Fr short (90-cm long) guiding catheters. In most cases, antegrade strategy was started using a single wire supported by a microcatheter followed by parallel-wire technique with intravascular ultrasound (IVUS)-guided wiring technique if necessary and wire stiffness escalation strategy. For retrograde approach, hydrophilic soft guidewire supported by a microcatheter was used in most cases to cross the collateral channels and exchanged if necessary with stiffer guidewire to cross retrogradely the CTO. Various techniques described previously in the literature^25,26 were used to achieve the retrograde approach, including direct retrograde crossing wire, kissing wire, knuckle wire, controlled antegrade retrograde tracking (CART), and reverse CART techniques. Externalization of retrograde wire was used in the retrograde crossing wire and reverse CART techniques. Stents were implanted to cover not only the whole CTO length but also the vessel diseased segments proximally and distally to the CTO lesion. DESs, mainly including the Cypher sirolimus-eluting stent (SES; Cordis Corporation), were used in all patients. After PCI, clopidogrel 75 mg/day and 100 mg aspirin were administrated for at least 1 year. 

Angiographic follow-up. All patients were planned to have a routine control coronary angiogram at a mean of 6 months. Quantitative coronary angiographic data were analyzed by an operator blinded to patient identities and binary angiographic restenosis was defined as >50% diameter stenosis. Both pre-PCI coronary angiogram and follow-up angiogram were compared and analyzed using the same angiographic views to determine the site of restenosis relative to the site of CTO lesion. In-stent restenosis was defined as diffuse if the length of restenosis was >50% of the total stent length. 

Clinical follow-up. Clinical follow-up was obtained in all patients every 6 months by direct contact of the patients and their relatives, interview of their referring physicians, and review of medical reports when patients had been hospitalized during follow-up. The following major events occurring after hospital discharge were searched and recorded: death (cardiac and non-cardiac), non-fatal stroke, stent thrombosis, non-fatal myocardial infarction, repeat PCI or surgical revascularization, hospitalization for cardiac failure, or unstable angina. 

Statistical analysis. Continuous variables are expressed as mean ± standard deviation. A 2-tailed Student’s t-test was used to test differences among continuous variables. Differences between categorical variables were analyzed with a Chi-square test or Fisher’s exact test. A P-value <.05 was considered significant. Multivariate correlates for the prediction of restenosis were analyzed with a logistic regression model. All univariate variables with a P-value <.1 were included in the model. The univariate model included both clinical variables (age, gender, diabetes, hypertension, smoking, dyslipidemia, left ventricular ejection fraction), angiographic variables (coronary artery location, in-stent CTO, CTO length, type of stump, calcifications, vessel tortuosity, ostial lesion, bifurcation lesion), and procedural variables (retrograde versus antegrade approach, stent type, number of stents, total stenting length, overlapping stents, maximal and minimal stent diameters, stent deployment maximal pressure). Statistical tests were performed with package software SPSS 7/0 (SPSS, Inc). 

Results

Table 1 summarizes the baseline clinical characteristics of our population. The majority of our patients (62%) were symptomatic with either stress chest pain or shortness of breath; these symptoms were demonstrated to be related to the occluded vessel by clinical examination, pulmonary and cardiac function exploration non-invasive techniques, and coronary angiogram results. In 38% of the population, ischemia was silent but documented with stress testing exercise or stress Thallium exercise. The duration of occlusion was determined based on a previous coronary angiogram or clinical data in 47% of cases with a mean occlusion duration of 49 ± 62 months (range, 5-300 months) and it was indeterminate in 53% of cases. Table 2 shows the angiographic characteristics of the 106 CTO lesions and procedural characteristics are displayed in Table 3. Among the 106 CTO lesions, SESs were used in 100 lesions (94%) and biolimus-eluting stents (BESs) were used in 6 lesions (6%).

Angiographic follow-up in the global population. All patients underwent follow-up coronary angiogram at 6 months. Among 106 CTO treated lesions with a mean stent length of 78 ± 32 mm (range, 23-174 mm), there were 19 in-stent restenoses (18%) at 6 months (18 SES and 1 BES) including 2 total in-stent reocclusions (1 in a SES and 1 in a BES). Restenosis type was diffuse in 3 cases (16%), with total occlusion in 2 of these 3 cases (11%). In-stent restenosis occurred exlusively at the site of CTO lesion in 26%, exclusively proximally or distally to the CTO lesion in 48%, and both at the site of CTO and outside the site of CTO in 26%.

Among the 19 restenoses, a total of 17 cases (90%) were successfully treated by repeat PCI using in-stent DES implantation, whereas 2 patients with diffuse restenosis (1 with total in-stent occlusion in a BES) were left on medical treatment (10%). The 19 restenosis cases did not differ from the non-restenotic group regarding risk factors including diabetes, left ejection fraction, vessel location of CTO, CTO length, in-stent CTO, type of stump (blunt versus tapered), vessel tortuosity, bifurcation, ostial location, antegrade versus retrograde approach, and number of stents implanted. Patients with restenosis were younger than those without restenosis (62 ± 8 years vs 67 ± 10 years; P=.029) and length of stenting was higher in the restenostic group when compared with the non-restenotic group (91 ± 28 mm vs 75 ± 33 mm; P=.059). Multivariate analysis showed that age and length of stents were independent predictors of restenosis (Exp[Coef], 0.939; 95% CI, 0.887-0.994; P=.031 and Exp[Coef], 1.015; 95% CI, 1.00-1.03; P=.056). 

Angiographic follow-up in the SES subgroup. Table 4 shows the characteristics of the 100 CTO lesions treated exclusively using SESs with a mean stented length of 79 ± 33 mm (range, 23-174 mm). Among these latter 100 SES CTO lesions, there were 18 in-stent restenoses at 6 months (18%) including 1 total in-stent reocclusion. Restenosis type was diffuse in 2 cases (11%) with total occlusion in 1 of these 2 diffusely restenotic cases. Among the 18 restenoses, a total of 16 cases (89%) were successfully treated by repeat PCI using in-stent DES implantation, whereas the 2 patients with diffuse restenosis were left on medical treatment (11%). Table 5 shows the comparison between restenotic and non-restenotic CTO lesions in the 100 SES CTOs. The 18 restenosis cases did not differ from the non-restenotic group regarding risk factors, including diabetes, left ejection fraction, vessel location of CTO, CTO length, in-stent CTO, type of stump (blunt versus tapered), vessel tortuosity, bifurcation, ostial location, antegrade versus retrograde approach, and number of stents implanted. Patients with restenosis were younger than those without restenosis (62 ± 8 years vs 67 ± 10 years; P=.039) and length of stenting was higher in the restenotic group when compared with the non-restenotic group (93 ± 28 mm vs 76 ± 33 mm; P=.051). Multivariate analysis showed that age and length of stents were independent predictors of restenosis (age: Exp[Coef], 0.939; 95% CI, 0.885-0.996; P=.035; length of stent: Exp[Coef], 1.017; 95% CI, 1.00-1.03; P=.045).

Clinical follow-up. Median clinical follow-up was 2 years (interquartile range, 1-4.3 years). Angiographic restenosis including 2 cases of total reocclusion was detected in 19 cases at RFUA at 6 months. Among the 19 restenosis cases, only 1 patient (1 of the 2 cases with total reocclusion) was symptomatic, with recurrence of stress chest pain a few days before control angiogram. Neither of the 2 reocclusion cases suffered a myocardial infarction. Two patients without CTO lesion restenosis at 6-month control angiogram underwent bypass graft surgery during follow-up (at 7 and 8 months, respectively) for development of a significant stenosis in the left main coronary artery.

Discussion

In the present study, we report the systematic follow-up angiographic outcome of chronic total coronary occlusions successfully treated by percutaneous angioplasty using a long stenting length. To our knowledge, RFUA has not been previously reported in such a large cohort of patients treated for true complex CTO with a length of SESs as long as in the present study. We found that the implantation of first-generation SESs over a very long length in true complex CTO is associated with acceptable restenosis rates. Our study may be used as a reference for future studies evaluating the efficacy of new-generation DESs in the treatment of such complex CTOs.

In our study, according to the EuroCTO club consensus,²² we included true CTOs defined by both TIMI grade 0 flow within the occluded segment and a duration of occlusion >3 months estimated from clinical events, symptoms, or previous coronary angiogram. Different definitions of CTO have, however, been used in previously published studies. Indeed, among the 11 major studies that have previously reported follow-up angiogram after successful CTO recanalization with SESs,^{9-12,14-19,21} CTO was defined by a duration of occlusion <3 months in 5 studies,^{9,14,15,18,21} the occlusion duration cut-off value was 2 weeks in 2 studies and 1 month in 3 studies, and patients with a TIMI grade 1 flow were also included in 3 studies.^14,15,21 Table 6 shows an overview of these 11 previous studies on CTO recanalization with SESs. 

In the ACROSS/TOSCA-4 multicenter trial,²⁷ a total of 200 total coronary occlusions were treated with SESs in 15 different centers in North America and were planned to have a 6-month follow-up angiogram. This latter study²⁷ did not, however, include only true chronic coronary occlusions since the inclusion criteria included only TIMI grade 0 or 1 flow without any duration criteria except very recent occlusions (<72 hours) which were excluded. In the recently published Canadian Multicenter Chronic Total Occlusion Registry,²⁴ CTO was also defined by an occlusion duration ≥6 weeks. In agreement with the consensus of the European CTO club,²² we believe that the cut-off value of 3 months should be kept to define a true CTO since there are data in the literature showing a significant drop in coronary recanalization success rates after 3 months of occlusion.²³ The mean occlusion duration of 49 months in our patients with known duration of occlusion was also particularly long when compared with other studies in which occlusion duration has been reported.^19,23 We also believe that a TIMI flow grade 1 should not be considered as a true CTO but rather as a functional chronic occlusion,²² which is usually much easier to recanalize. 

According to the definitions of CTO lesions adopted by the European CTO club²² and in agreement with previously published studies,^23,24 we also included patients in whom there was no clinical evidence of the time the occlusion developed or no previous coronary angiogram, but in whom angiographic findings were consistent with a CTO. Indeterminate duration of occlusion was found in 53% of our patients. Such a proportion of CTOs with indeterminate occlusion duration is a common finding. Indeed, occlusion duration remains indeterminate in 40%-60% of patients with typical angiographic aspect of CTO.^18,19,23,24 CTOs with indeterminate occlusion duration are usually found by coronary angiogram performed after screening electrocardiogram or stress testing most often in asymptomatic patients. When there is no history of acute coronary syndrome or even no history of stable chest pain with a precise onset, there is no reason to estimate indeterminate duration occlusion as more recent than 3 months. In addition, Barlis et al²³ showed that the overall success rate of PCI in patients with indeterminate occlusion duration is particularly low and comparable with that of CTO with a very long occlusion of known duration. Table 7 summarizes the classification we use in our own institution to define the different types of coronary artery occlusion. In our practice, we include both total and functional occlusions of indeterminate duration (ITO and IFO, respectively) in the subgroups of chronic total occlusions (CTO) and chronic functional occlusions (CFO). 

The definition used for an immediate angiographic success was not provided in all studies on follow-up angiogram after successful CTO recanalization with SESs^{9-12,14-19,21} and a post-PCI TIMI grade 2 flow was accepted as a success in 2 of these latter studies.^12,19 In agreement with other studies on recanalization of acute coronary occlusion at the acute phase of myocardial infarction that have demonstrated that a TIMI grade 2 flow cannot be considered as a repermeabilized vessel,²⁸ we defined post-PCI angiographic success in our study with a TIMI grade 3 flow and residual stenosis <30%.  

Our study reports a series of 100 true CTOs successfully recanalized with SESs and systematically controlled by coronary angiogram at 6 months. One previously published study by Ge et al¹¹ has included a similar cohort of 101 RFUAs after successful recanalization of true CTOs by PCI using SESs, but with a mean stent length (42 mm) and a number of stents (1.4)  that were both much lower than in our own study and without any evaluation of restenosis predictors, as in our study. 

The restenosis rate at 6 months was relatively low (18%) in our DES group despite a long mean stenting length (79 mm in the 100 CTOs with SESs) with a high mean number of stents implanted (≈4) in the SES group and a high proportion of overlapping stents (90%). As shown in Table 6, lower restenosis rates ranging from 0%-14% have been reported after recanalization of CTOs with SESs in 9 other studies.^{9-11,14-18,21} However, except the study by Ge et al,¹¹ the sample population of the other studies^{9,10,14-18,21} was much smaller when compared with our study, with fewer than 50 patients in 6 studies.^9,10,14-17 In addition, the mean stent length and mean number of stents implanted in all other studies previously reported with lower restenosis rates^{9-11,14-18,21} were much smaller (range, 23-45 mm and 1.4-2.2 stents, respectively) than those of our own study (79 mm and 3.9 stents). In 2 other studies^12,19 with a mean total stent length >50 mm (51 mm and 63 mm, respectively), restenosis rates at 6 months were close (19% and 17%, respectively) to those found in our study. To our knowledge, there is only 1 previously published study on CTOs recanalized with the use of DESs with a mean total stent length similar to our study.²⁹ In their work, Wöhrle et al²⁹ reported a restenosis rate of 11% at 6 months in a small cohort of 47 patients angiographically controlled after successful recanalization of true CTOs using everolimus-eluting stents (which is newer-generation DES) with a mean stent length of 79 mm. 

In our study, the total stent length was much greater than the CTO length, with a ratio of 3 in the SES group. A total stent length greater than CTO length has been previously reported by other investigators, with length ratios ranging from 1.5-2.2.^9-12,19 The implantation of a long stenting length is often necessary in CTO recanalization, since CTO vessels are often diffusely diseased and require multiple stents over a long length to fully cover all diseased segments. In our patients, severely diffusely diseased vessels accounted for a high stent length/CTO length ratio. Interestingly, the restenosis site was almost equally distributed between the CTO lesion and the segments proximal and distal to the CTO. This latter finding suggests that the CTO lesion per se does not necessarily lead to restenosis rates higher than those observed in adjacent diseased non-totally occluded segments.

The 6-month restenosis rate of 18% found in our study in which conventional CTO antegrade and retrograde techniques (81% and 19%, respectively) were used with a long length of SESs (79 mm) remains much lower than reported when using the guided-STAR technique (54%) despite a shorter stenting length.²⁰ Interestingly, we observed that the type of restenosis after SESs, despite a very long stent length, was focal in the majority of cases (≈90%), with a mean ratio of restenosis to stent length equal to 0.15. A greater proportion of focal-type versus diffuse-type restenosis after CTO recanalizations with SESs has been reported previously by other investigators.^11,19 In addition, restenosis was successfully treated in our study by repeat angioplasty in almost 90% of cases. 

As well, despite a very long stenting length, the rate of total reocclusion was acceptable in our study since it was 2% in our total population with DESs and it was 1% in the subgroup of SESs. Rates of occlusion ranging from 0%-12% have been reported in previous series of CTO recanalization with shorter lengths of SESs,^{9-12,14,15,18,19} with rates of 5.5% and 12%, respectively, in the 2 studies in which the stent length was >50 mm.^12,19 

The decision to treat the restenosis by repeat PCI was based on angiographic findings in the majority of cases, since only 1 patient with restenosis (total reocclusion) was symptomatic at the time of control angiogram. Therefore, if we exclude the revascularizations triggered by the protocol-mandated angiographic follow-up findings (the “occulo-stenotic reflex”), the rate of target lesion revascularization driven by clinical ischemia was extremely low, since it was less than 1%. Such a very low clinically-driven target vessel revascularization rate may be explained in part by the fact that a significant proportion of patients was already asymptomatic before recanalization of their chronically occluded vessel. As well, the other major cardiovascular events during follow-up were very rare, since they only included 2 cardiac surgical interventions for development of left main stenosis not suitable for PCI. 

In the DES group, we found that patients with restenosis were younger that those witout restenosis and multivariate analysis showed that young age and very long stent length were the only independent predictors of restenosis. All other variables analyzed, including risk factors, left ventricular function, vessel location, characteristics of the CTO, and strategy used (anterograde vs retrograde), did not differ between restenotic and non-restenotic CTOs. Our results regarding length of stents as a restenosis predictor are in close agreement with previous studies.^12,19 To our knowledge, no previous study has reported young age as a predictor of restenosis after CTO recanalization with DESs. This latter finding has to be evaluated in further studies and if confirmed it should be taken into account when one considers the indication of a CTO recanalization, especially in patients with multivessel disease. 

In summary, our results suggest that a “full-metal jacket” performed with DESs can be used in complex coronary CTOs with acceptable restenosis rates, including total reocclusions, with the possibility to successfully treat restenosis by repeat PCI. It remains to be seen whether new-generation DESs will significantly improve these results obtained with first-generation SESs. 

Study limitations. Due to the low restenosis rate, the statistical robustness of the multivariate analysis we used, which included a variety of variables, is certainly limited and further studies including larger patients cohorts are necessary to confirm our findings regarding restenosis predictors.

Conclusion

Our study suggests that angiographic restenosis rates remain relatively low at 6 months after successful recanalization of complex coronary CTOs with a very long stenting length if DESs are used. 

References

1. Christofferson RD, Lehmann KG, Martin GV, Every N, Caldwell JH, Kapadia SR. Effect of chronic total coronary occlusion on treatment strategy. Am J Cardiol. 2005;95(9):1088-1091.
2. Kahn JK. Angiographic suitability for catheter revascularization of total coronary occlusions in patients from a community hospital setting. Am Heart J. 1993;126(3 Pt 1):561-564.
3. Grantham JA, Marso SP, Spertus J, House J, Holmes DR Jr, Rutherford BD. Chronic total occlusion angioplasty in the United States. JACC Cardiovasc Interv. 2009;2(6):479-486.
4. Sirnes PA, Golf S, Myreng Y, et al. Sustained benefit of stentin chronic coronary occlusion: long-term clinical follow-up of the Stenting in Chronic Coronary Occlusion (SICCO) study. J Am Coll Cardiol. 1998;32(2):305-310.
5. Colmenarez HJ, Escaned J, Fernández C, et al. Efficacy and safety of drug-eluting stents in chronic total coronary occlusion recanalization: a systematic review and meta-analysis. J Am Coll Cardiol. 2010;55(17):1854-1866.
6. Rubartelli P, Verna E, Niccoli L, et al. Coronary stent implantation is superior to balloon angioplasty for chronic coronary occlusions: six-year clinical follow-up of the GISSOC trial. J Am Coll Cardiol. 2003;41(9):1488-1492.
7. Werner GS, Krack A, Schwarz G, Prochnau D, Betge S, Figulla HR. Prevention of lesion recurrence in chronic total coronary occlusions by paclitaxel-eluting stents. J Am Coll Cardiol. 2004;44(12):2301-2306.
8. Hoye A, Tanabe K, Lemos PA, et al. Significant reduction in restenosis after the use of sirolimus-eluting stents in the treatment of chronic total occlusions. J Am Coll Cardiol. 2004;43(11):1954-1958.
9. Nakamura S, Muthusamy TS, Bae JH, Cahyadi YH, Udayachalerm W, Tresukolol D. Impact of sirolimus-eluting stent on the outcome of patients with chronic total occlusions. Am J Cardiol. 2005;95(2):161-166.
10. Ge L, Iakovou I, Cosgrave J, et al. Immediate and mid-term outcomes of sirolimus-eluting stent implantation for chronic total occlusions. Eur Heart J. 2005;26(11):1056-1062.
11. Migliorini A, Moschi G, Vergara R, Parodi G, Carrabba N, Antoniucci D. Drug-eluting stent-supported percutaneous coronary intervention for chronic total coronary occlusion. Catheter Cardiovasc Interv. 2006;67(3):344-348.
12. Werner GS, Schwarz G, Prochnau D, et al. Paclitaxel-eluting stents for the treatment of chronic total coronary occlusions: a strategy of extensive lesion coverage with drug-eluting stents. Catheter Cardiovasc Interv. 2006;67(1):1-9.
13. Suttorp MJ, Laarman GJ, Rahel BM, et al. Primary Stenting of Totally Occluded Native Coronary Arteries II (PRISON II): a randomized comparison of bare metal stent implantation with sirolimus-eluting stent implantation for the treatment of total coronary occlusions. Circulation. 2006;114(9):921-928.
14. Kelbaek H, Helqvist S, Thuesen L, et al. Sirolimus versus bare metal stent implantation in patients with total coronary occlusions: subgroup analysis of the Stenting Coronary Arteries in Non-Stress/Benestent Disease (SCANDSTENT) trial. Am Heart J. 2006;152(5):882-886.
15. Lotan C, Alamagor Y, Kuiper K, Suttorp MJ, Wijns W. Sirolimus-eluting stent in chronic total occlusion: the SICTO study. J Interv Cardiol. 2006;19(4):307-312.
16. Garcia-Garcıa HM, Daemen J, Kukreja N, et al. Three-year clinical outcomes after coronary stenting of chronic total occlusion using sirolimus-eluting stents: insights from the Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital (RESEARCH) registry. Cathet Cardiovasc Intervent. 2007;70(5):635-639.
17. Rubartelli P, Petronio AS, Guiducci V, et al; Gruppo Italiano di Studio sullo Stent nelle Occlusioni Coronariche II GISE Investigators. Comparison of sirolimus-eluting and bare metal stent for treatment of patients with total coronary occlusions: results of the GISSOC II-GISE multicentre randomized trial. Eur Heart J. 2010;31(16):2014-2020.
18. Galassi AR, Tomasello SD, Costanzo L, Campisano MB, Barrano G, Tamburino C. Long-term clinical and angiographic results of Sirolimus-Eluting Stent in Complex Coronary Chronic Total Occlusion Revascularization: the SECTOR registry. J Interv Cardiol2011;24(5):426-436.
19. Godino C, Latib A, Economou FI, et al. Coronary chronic total occlusions: mid-term comparison of clinical outcome following the use of the guided-STAR technique and conventional anterograde approaches. Catheter Cardiovasc Interv. 2012;79(1):20-27.
20. Park HJ, Kim HY, Lee JM, et al. Randomized comparison of the efficacy and safety of zotarolimus-eluting stents vs. sirolimus-eluting stents for percutaneous coronary intervention in chronic total occlusion — CAtholic Total Occlusion Study (CATOS) trial. Circ J2012;76(4):868-875.
21. Di Mario C, Werner GS, Sianos G, et al; the EuroCTO club. European perspective in the recanalisation of chronic total occlusions (CTO): consensu document from the EuroCTO Club. EuroIntervention. 2007;3(1):30-43.
22. Barlis P, Kaplan S, Dimopoulos K, Tanigawa J, Schultz C, Di Mario C. An indeterminate occlusion duration predicts procedural failure in the recanalization of coronary chcronic total occlusions. Catheter Cardiovasc Interv. 2008;71(5):621-628.
23. Fefer P, Knudtson M, Cheema A, et al. Current perspectives on coronary chronic total occlusions. The Canadian Multicenter chronic total occlusion registry. J Am Coll Cardiol. 2012;59(11):991-997.
24. Surmely JF, Tsuchikane E, Katoh O, et al. New concept for CTO recanalization using controlled anterograde and retrograde subintimal tracking: the CART technique. J Invasive Cardiol. 2006;18(7):334-338.
25. Saito S. Different strategies of retrograde approach in coronary angioplasty for chronic total occlusion. Catheter Cardiovasc Interv. 2008;71(1):8-19.
26. Kandzari DE, Rao SV, Moses JW, et al; ACROSS/TOSCA-4 Investigators. Clinical and angiographic outcomes with sirolimus-eluting stents in total coronary occlusions: the ACROSS/TOSCA-4 (Approaches to Chronic Occlusions With Sirolimus-Eluting Stents/Total Occlusion Study of Coronary Arteries-4) trial. JACC Cardiovasc Interv. 2009;2(2):97-106.
27. Reiner JS, Lundergan CF, Fung A, et al. Evolution of early TIMI 2 flow after thrombolysis for acute myocardial infarction. GUSTO-1 Angiographic Investigators. Circulation1996;94(10):2441-2446.
28. Wöhrle J, Rottbauer W, Imhof A. Everolimus-eluting stents for treatment of chronic total coronary occlusions. Clin Res Cardiol2012;101(1):23-28.

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From the Division of Cardiology, University of Saint Etienne, Saint Etienne, France. 

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted January 3, 2013, provisional acceptance given March 4, 2013, final version accepted April 12, 2013.

Address for correspondence: Pr Karl Isaaz, Service de cardiologie, Hôpital Nord, Centre Hospitalo-Universitaire de Saint Etienne, 42055 Saint Etienne Cedex 2, France. Email: isaaz@univ-st-etienne.fr