Provisional TAP-Stenting Strategy to Treat Bifurcated Lesions with Drug-Eluting Stents (Full title below)

Provisional TAP-Stenting Strategy to Treat Bifurcated Lesions with Drug-Eluting Stents: One-Year Clinical Results of a Prospective Registry ABSTRACT: Objective. To assess the clinical outcome of unselected patients undergoing drug-eluting stent (DES) implantation on bifurcated lesions using a “provisional T And small Protrusion (TAP)” stenting strategy. Methods. Consecutive patients undergoing DES implantation on one major bifurcation lesion were treated by main-vessel (MV) stenting, followed (if needed) by side-branch (SB) rewiring (with a “pullback” technique) and kissing balloon. SB stenting was performed according to the TAP-technique in selected cases. The endpoint of the study was a 12-month incidence of major adverse cardiac events (MACE) defined as cardiac death, myocardial infarction (MI), stent thrombosis and target vessel revascularization (TVR). Results. The study population included 266 patients (9% unprotected left main). Only 19 patients (7.1%) (with more complex angiographic features) received stents in both the MV and SB using the TAP-technique. Overall, 22 (8.2%) patients had MACE at 1 year. Observed, non-hierarchical MACE were: 1 (0.4%) cardiac death, 11 (4.1%) MI, 2 probable stent thromboses and 12 (4.5%) TVRs. Post-procedural troponin T increase and adverse events up to 12 months were similar between patients treated by MV stenting only or double stenting. Conclusions. In unselected patients undergoing DES implantation on bifurcated lesions, a provisional TAP-stenting strategy (with a low rate of SB stenting) appears to be safe and effective. J INVASIVE CARDIOL 2009;21:532–537 Key words: percutaneous coronary intervention, bifurcated lesions, side branch stenting Drug-eluting stents (DES) have been shown to reduce restenosis in bifurcated lesions treated by percutaneous coronary intervention (PCI).1,2 However, the best technique to implant DES in bifurcated lesions has not been ascertained.2 Overall, the strategy aimed at implanting a single stent does not appear to be inferior in terms of clinical outcome to complex techniques of double-stent implantation.3,4 Provisional T-stenting is thus the most widely adopted technique at present. However, when a second stent is required on the side branch (SB) after main-vessel (MV) stenting, T-stenting is associated with some technical drawbacks that include inappropriate SB ostium coverage or unanticipated protrusion of the SB stent into the MV.5 Recently, a modification of the T-stenting technique, namely the T-stenting and small protrusion technique (TAP), has been described, and shows evidence of overcoming the inherent limitations of the classic method.6 The present study aimed at assessing the clinical outcomes of patients undergoing percutaneous treatment of coronary bifurcation lesions using a systematic “provisional-TAP stenting” strategy with DES. Methods Study population and protocol. We prospectively assessed the clinical outcomes of patients undergoing PCI of one major bifurcation lesion by provisional TAP-stenting with DES. From March 1, 2005 to February 28, 2007, patients ≥ 18 years of age with stable or unstable angina undergoing PCI with either a sirolimus-eluting stent (Cypher Select, Cordis Corp., Miami Lakes, Florida), a paclitaxel-eluting stent (Taxus Liberté, Boston Scientific Corp., Natick, Mass.), a zotarolimus-eluting stent (Endeavor Sprint, Medtronic, Inc., Minneapolis, Minn.), or an everolimus-eluting stent (Xience V, Abbott Vascular, Santa Clara, Calif.) were considered for enrollment (since these stent types had been routinely used in clinical practice during the study period). According to our institutional guidelines, patients undergoing PCI on bifurcated lesions are routinely treated with DES in the absence of the following conditions: acute myocardial infarction (AMI) within 24 hours from symptom onset and limited compliance with prolonged dual antiplatelet therapy (elective surgery planned, recent bleeding, significant gastroduodenal peptic disease, etc.). Angiographic eligibility required a de novo target lesion with a visual reference vessel diameter of 2.25–4.0 mm for both the MV and SB. Bifurcated lesions were classified according to the Medina classification.7 Clinical, angiographic and procedural characteristics were prospectively entered into a structured electronic database (Cardio-planet V.3.0.8, Ebit Aet S.p.A, Genoa, Italy). The study complied with the Declaration of Helsinki and was approved by our center’s institutional review board. All patients enrolled gave informed consent to participate in the study. Percutaneous coronary interventions. All procedures were performed according to the provisional TAP-stenting strategy. This means that all patients were treated by MV stenting first under SB protection with a jailed guidewire technique, then SB rewiring and kissing balloon were performed if considered necessary by the operator (kissing balloon was systematically attempted in cases of large territories supplied by the SB or when the SB exhibited flow impairment after MV stenting). Then, if judged necessary by the operator, a second stent was implanted in the SB employing the TAP-stenting technique. A conservative approach was generally adopted and a SB stent was implanted only in the presence of SB dissections or significant residual stenosis in relevant vessels. The key steps of the technique adopted during the study are represented in Figure 1, which shows the angiographic images obtained by in vitro testing using a silicon phantom coronary bifurcation (tube luminal diameters: 4 mm proximal MV, 3.5 mm distal MV, 2.5 mm SB; angulation between MV and SB: 30°). In particular, during SB rewiring, careful attention was given to cross the MV struts in the distal part of the SB ostium. To facilitate this, rewiring was performed (always using a BMW Universal by Abbott Vascular as the first choice) by using a pullback technique to get into the ostium (Figure 1). Such a technique, when successful, should provide the best scaffolding of a SB ostium by the MV stent struts, thus reducing the need for a second stent. When the proximal segment of the MV stent appears underexpanded or difficulties in rewiring are encountered, MV postdilatation with a short balloon is performed to push the MV side stent struts into the SB ostium using the proximal optimization technique.8 As previously mentioned, the second stent that was eventually needed was implanted using the TAP technique which, as recently described,6 is a modification of the classic T-stenting technique based on the intentional minimal protrusion of the SB stent within the MV (after MV stenting and kissing balloon). As showed in the Figure 1, the technique guarantees complete coverage of the SB ostium as well as the ability to perform final kissing balloon (as the MV balloon necessary for final kissing is placed in position before SB stent deployment). The selection of DES type was left to the operator’s discretion. Procedural success was defined by angiographically assessed residual stenosis 50%) angiographic stenosis. Study endpoints. The endpoint of this study was the 12-month incidence of major adverse cardiac events (MACE) including cardiac death, non-fatal myocardial infarction (MI), stent thrombosis and target vessel revascularization (TVR). Deaths of unknown cause were considered to be of cardiovascular origin. MI included post-procedural MI and MI during clinical follow up. Post-procedural MI was defined as a rise of CK-MB > 3 times the 99th percentile upper reference limit during the 48 hours after PCI. Thereafter, the universal definition was used for MI, which favors troponin as a biomarker for myocardial necrosis9 and any rise in troponin T levels above the upper normal limit in the setting of clinical suspicion of myocardial ischemia. TVR was defined as repeated clinically driven revascularization by either PCI or coronary artery bypass grafting (CABG) involving the treated vessel. Stent thrombosis was classified by the Academic Research Consortium definition as definite, probable or possible, and as early (0–30 days), late (31–360 days) or very late (> 360 days).10 The definition of definite stent thrombosis required the presence of an acute coronary syndrome with angiographic or autopsy evidence of thrombus or occlusion. Probable stent thrombosis included unexplained deaths within 30 days after the procedure or any acute MI involving the target vessel territory without angiographic confirmation. Possible stent thrombosis included all unexplained deaths occurring > 30 days after the procedure. Statistical analysis. Continuous variables with a normal distribution according to the Kolmogorov-Smirnov test were compared by the student’s t-test while skewed ones were compared using the Mann-Whitney U test. Categorical variables were compared by Pearson’s chi-square test or Fisher’s exact test as appropriate. Dichotomized clinical and procedural variables were considered as potential risk predictors in exploratory analysis, with Cox proportional hazard regression being applied to assess the association of these variables with 12-month MACE. Variables included in the multivariable model were those showing a significant association or a clear trend toward association (p Results Patients. During the study period, 385 patients with angiographic documentation of coronary artery disease involving one major bifurcation were deemed eligible for PCI. In 89 of them, a bare-metal stent was used. Of the remaining 296 patients, 21 were enrolled in other study protocols (with DES not specified in the present study protocol or testing other techniques), and 9 (usually large vessels with Medina 0.1.1 lesions) were treated with a simultaneous kissing-stent technique. Overall, 266 patients (221 men, age 65 ± 10 years) were enrolled in the registry. Their general characteristics are summarized in Table 1. Briefly, 23% were diabetics, 64% had multivessel disease and 21% had reduced (Discussion This study assessed the outcomes of patients with coronary bifurcation lesions treated according to a systematic provisional TAP strategy with DES. Its main findings are: 1) satisfactory clinical outcomes were achieved in the overall cohort applying a strategy aimed at keeping the rate of double stenting very low; 2) no detrimental effect from the TAP technique was found on the clinical outcomes of selected patients (with more complex lesions) who were considered to need a second stent. Historically, treatment of coronary bifurcation lesions, which accounts for approximately 15–20% of PCIs performed today, has been associated with poorer outcomes than those obtained when treating less complex lesions.11 With the advent of DES, the better results achieved in less complex lesions have been extended to bifurcation stenting as well.1,2 The desire for optimal angiographic results and the perception that SB stenting may lead to better long-term success have led to the development of several two-stent techniques.12 However, data from randomized studies comparing simple versus complex strategies failed to show a clear advantage of routine stenting in both branches over provisional stenting of the MV only.13,14 Moreover, a meta-analysis of 963 patients undergoing PCI of a bifurcation lesion confirmed that both approaches to treatment are comparable.4 Dedicated bifurcation stents have also been developed,15 but their clinical applicability and benefit require broader demonstration than what is currently available. All in all, current recommendations favor a simple stenting strategy, with provisional T-stenting being the most commonly adopted technique.3 However, when a second stent in the SB is required, standard T-stenting is associated with the risk of incomplete coverage of the SB ostium (especially when there is an acute angulation between the MV and SB).5 Imperfect SB ostial coverage is deemed to be involved in the development of restenosis.12 The TAP technique as developed to overcome this problem.12 This modification of the classic T-stenting technique (after stenting the MV and successive kissing balloon) is based on the intentional minimal protrusion of the SB stent into the MV, and final kissing balloon is performed using the balloon previously placed in the MV. The final kissing balloon, which is warranted in this technique, reshapes the protruding SB stent struts and creates a small, single-strut neocarina layer that does not impair the MV lumen.6 The main advantage of the TAP technique over more complex two-stent strategies is the full coverage of the vessel ostium without large double or triple strut layers (unlike the culotte and crush techniques). Another positive aspect of the TAP technique is its achievability using any of the major available DES and a 6 French guiding catheter (with appropriate selection of low-profile balloon catheters), thus allowing a radial approach, which was performed in more than half of the patients enrolled in the present study. The possible stent thrombosis risk associated with the creation of a single-layer neocarina does not appear to be greater, as suggested by the follow-up data from this study, in which no definite stent thrombosis was observed and the 2 probable stent thromboses were not observed in patients who underwent TAP stenting. Moreover, at up to 12-month clinical follow up, only 1 (asymptomatic post-procedural) MI and 1 TLR was observed in patients treated with TAP stenting. These data seem to differ from those recently reported by Routledge et al who employed a conventional provisional T-stenting strategy with a 28% rate of crossover to double stenting and observed significantly worse clinical outcomes in patients who ultimately received 2 stents.16 Such observations, however, should be regarded as speculative, as the number of patients treated with double stenting in our study is too small to allow a reliable estimate of clinical outcomes. Moreover, a lower rate of double stenting may be associated with a higher rate of SB residual stenosis and possibly residual ischemia. However, since confounders (type of stent used, completeness of myocardial revascularization, etc.) may be relevant, we planned to evaluate this issue in a dedicated protocol (acronym: SEA-SIDE, www.clinicaltrial.org). Despite the clinical characteristics of the patients (almost 40% had unstable presentation and about two-thirds had multivessel disease), very few in-hospital events were observed and consisted of post-procedural NSTEMI according to routine CK-MB assessment. Of note, a post-procedural increase of the highly sensitive cardiac troponin levels was also similar between patients who received an MV stent only or double stenting. Finally, SB occlusion, which is an infrequently reported angiographic complication in published papers on coronary bifurcation lesions, did occurred in 3 patients and was associated with a significant periprocedural MI, suggesting that efforts to prevent its occurrence while adopting a provisional strategy of SB intervention are claimed. Study limitations. This study was designed as an observational registry. No direct comparisons between different strategies were implemented and no conclusion on the optimal technique to treat bifurcated lesions should be derived. However, the use of this kind of protocol may help in the design of future randomized studies and may provide useful information about the applicability of this technical strategy for unselected patients. The lack of strict protocol-defined criteria for SB stenting and the possibility of implanting a 2.25 mm SB stent (unavailable in some countries) may limit the potential to extrapolate the results observed in the present registry. Another limitation of the present study is related to the lack of intravascular ultrasound evaluation. This limits both the accuracy of bifurcation plaque morphology assessment and the estimation of the procedural result achieved. On the other hand, as the majority of catheterization laboratories do not routinely perform intravascular ultrasound evaluations in bifurcation PCI, it is worth noting that the reported clinical results were obtained in the presence of angiographic guidance only. Angiographic follow up was not performed, and extended clinical follow up beyond 1 year was obtained in only one-quarter of patients such that the angiographic efficacy and very long-term clinical results of the investigated approach could not be evaluated. Conclusions In an unselected population of patients undergoing DES implantation in bifurcated lesions, a provisional TAP stenting strategy, characterized by a low rate of SB stenting, appears to be safe and effective. Prospective, randomized trials are necessary to assess the possible clinical advantages of this strategy in the treatment of patients with bifurcated lesions. From the Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy. The authors report no conflicts of interest regarding the content herein. Manuscript submitted April 2, 2009, provisional acceptance given May 18, 2009, final version accepted June 24, 2009. Address for correspondence: Francesco Burzotta, MD, PhD, Via Prati Fiscali 158, 00141 Rome, Italy. E-mail: f.burzotta@rm.unicatt.it

1. Colombo A, Moses JW, Morice MC et al. Randomized study to evaluate sirolimus-eluting stents implanted at coronary bifurcation lesions. Circulation 2004;109:1244–1249.

2. Thuesen L, Kelbaek H, Kløvgaard L et al; SCANDSTENT Investigators. Comparison of sirolimus-eluting and bare metal stents in coronary bifurcation lesions: Subgroup analysis of the Stenting Coronary Arteries in Non-Stress/Benestent Disease Trial (SCANDSTENT). Am Heart J 2006;152:1140–1145.

3. Louvard Y, Thomas M, Dzavik V et al. Classification of coronary artery bifurcation lesions and treatments: Time for a consensus! Catheter Cardiovasc Interv 2008;71:175–183.

4. Niccoli G, Ferrante G, Porto I, et al. Coronary bifurcation lesions: To stent one branch or both? A meta-analysis of patients treated with drug-eluting stents. Int J Cardiol 2009 (Epub before print).

5. Ormiston JA, Webster MW, El Jack S, et al. Drug-eluting stents for coronary bifurcations: bench testing of provisional side-branch strategies. Catheter Cardiovasc Interv 2006;67:49–55.

6. Burzotta F, Gwon HC, Hahn JY, et al. Modified T-stenting with intentional protrusion of the side-branch stent within the main vessel stent to ensure ostial coverage and facilitate final kissing balloon: The T-stenting and small protrusion technique (TAP-stenting). Report of bench testing and first clinical Italian-Korean two-centre experience. Catheter Cardiovasc Interv 2007;70:75–82.

7. Medina A, Suárez de Lezo J, Pan M. Una clasificación simple de las lesiones coronarias en bifurcación. Rev Esp Cardiol 2006;59:183.

8. Darremont O. Personal communication at European Bifurcation Club Meeting 2007.

9. Thygesen K, Alpert JS, White HD, on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. Eur Heart J 2007;28:2525–2538.

10. Cutlip DE, Windecker S, Mehran R, et al, on behalf of the Academic Research Consortium. Clinical end points in coronary stent trials: A case for standardized definitions. Circulation 2007;115:2344–2351.

11. Latib A, Colombo A. Bifurcation disease: What do we know, what should we do? J Am Coll Cardiol Intv 2008;1:218–226.

12. Iakovou I, Ge L, Colombo A. Contemporary stent treatment of coronary bifurcations. J Am Coll Cardiol 2005;46:1446–1455.

13. Steigen TK, Maeng M, Wiseth R, et al. Randomized study on simple versus complex stenting of coronary artery bifurcation lesions: The Nordic bifurcation study. Circulation 2006;114:1955–1961.

14. Pan M, de Lezo JS, Medina A, et al. Rapamycin-eluting stents for the treatment of bifurcated coronary lesions: A randomized comparison of a simple versus complex strategy. Am Heart J 2004;148:857–864.

15. Latib A, Colombo A, Sangiorgi G. Bifurcation stenting: Current strategies and new devices. Heart 2008. In press.

16. Routledge HC, Morice MC, Lefèvre T, et al. 2-Year Outcome of patients treated for bifurcation coronary disease with provisional side branch T-stenting using drug-eluting stents. J Am Coll Cardiol Intv 2008;1:358–365.