Percutaneous coronary intervention (PCI) on coronary bifurcation lesions (CBLs) which account for 15–20% of interventions has been considered as a challenging task for interventionists.1–3 Despite the implementation of the numerous techniques (T-stenting, V-stenting, crush stenting, and culotte stenting) to stent both the main branch (MB) and the side branch (SB), none of them, even in the era of drug-eluting stent (DES), has shown clinical and angiographic superiority to the simpler approach just by stenting the parent vessel (PV) and its MB with provisional T-stenting of the SB in case of dissection or severe residual stenosis.4–12 Nonetheless, the safety and efficacy of the simpler approach have been questioned particularly in setting of severe CBL with bigger SB.10–13 More recently, the double-kissing-crush stenting (DKS), known as an optimal dual-stenting technique, has been showed much easier to achieve final balloon kissing (FBK), thus remarkably reducing the SB residual stenosis and restenosis,14–16 but crushed stent layers and incomplete stent coverage remain a potential risk of restenosis or thrombosis. Although traditional culotte stenting, as first described decades ago, may be superior to crush techniques by no crushed stent layers against the PV wall and evenly complete stent coverage of the whole lesion, it has not been widely used clinically due to its technical complexity, potential risk of acute branch closure and relatively few outcome data available.17–19
To address the above-mentioned questions, in the present study we first developed a modified culotte stenting technique (MCS), tested its technical feasibility and reliability and observed 9-month clinical and angiographic outcomes in the treatment of the CBLs that needed stenting both branches with DESs.
Patients and study protocol
This prospective pilot study was conducted in our hospital from October 2009 to March 2010. A total of 34 consecutive patients eligible for the enrolled criteria were included. All patients were first assigned to receive MCS for CBL interventions (per MCS), and for the procedural safety might be switched to receive crush techniques such as DKS in case of temporally acute branch occlusion with failure to rewiring the compromising branch (per protocol).
The study protocol was approved by the Ethics Committee of Fujian Medical University and conformed to the principles outlined in Declaration of Helsinki. All patients gave written informed consent.
Men and women, aged 18 years or older, with CBLs, were considered eligible for enrollment. A CBL was defined according to Lefevre-Medina's classifications20,21 and could be located in the left main stem (LM), the anterior descending artery (LAD) and the left circumflex artery (LCX), LAD and a diagonal branch (DB), LCX and an obtuse marginal branch (OM), or the right coronary artery (RCA), the posterior descending artery (PDA) and the postero-lateral artery (PLA). The diameter of the MB and the SB by visual estimate should be 2.5 mm and 2.0 mm, respectively, and the diameter difference between two branches should be 0.5 mm.
Patients with ST-segment elevation acute myocardial infarction (STEMI) within 24 hours, life expectancy <1 year, allergy to any of the drugs used (aspirin, clopidogrel, sirolimus, zotarolimus and paclitaxel) were excluded.
All patients received appropriate pretreatment of aspirin and clopidogrel with a loading dose if indicated. Postprocedurally, aspirin was maintained indefinitely, and clopidogrel for 12 months routinely. Procedural heparin administration was according to the hospital routine, and activated clotting time control was not mandatory. Glycoprotein receptor antagonists were used at the discretion of the operator. The DESs (Firebird, Microport Inc., Shanghai, China; Partner, Lepu Medical Co. Ltd., Beijing, China; Excel, JW Medical Co. Inc., Weihai, China; Cypher Slect, Cordis/Johnson & Johnson Inc., USA; Taxus, Boston Scientific Co., USA; Resolute, Medtronic Inc., USA) were used in the study with a preference of open-cell-design stents.
The radial access was used routinely with 6/7F guiding catheters, and the femoral approach with 7/8F guiding catheters only used in case of delivering larger profile stents or at the discretion of the operator. Implantation of additional stents to cover the whole lesion or to cover a dissection was allowed. Different types of DESs in the same vessel were not allowed.
The MCS main steps are demonstrated in Figure 1 schematically, and in Figure 2 in an unstable angina patient with a severe true LAD-D1 CBL and in Figure 3 in a patient with extensive ST-elevation and episodes of Adam-Stroke syndrome who had CAG findings of Medina's (1,1,1) CBL, located at LM-LAD-LCX. The detailed procedures were described as follows: (1) beginning with wiring the MB and the SB; (2) predilating or not pre-dilating the branches at the discretion of the operator, but avoiding pretreatment (conventional balloon or cutting balloon) of segments not covered by stent; (3) pre-imbedding a balloon in the MB and advancing the first stent into the SB with protrusion of 1–2 mm into the MB; (4) inflating the stent balloon with lower pressure to stent the SB first, which might jail the pre-imbedded balloon and wire in the MB; (5) removing the stent balloon out of the SB, wiring the MB via a side-hole of the expanded SB stent with confirmation of the wire in its true lumen; (6) then removing the pre-imbedded balloon out of the MB while keeping the jailed wire until a balloon (the pre-imbedded balloon) has passed and enlarged the stent side-hole, allowing passage of the subsequent stent; (7) advancing and positioning the MB stent at least 2 mm proximal to the expanded SB stent; (8) deploying the MB stent with higher pressure, and then advancing the deflated stent balloon deeply into the MB (distal to the SB ostium) just for subsequent rewiring SB easily; (9) rewiring and ballooning SB with higher pressure, and then performing a FBK at the end of the procedure with appropriate inflation pressure; by using or not using non-compliance balloon at the discretion of the operator; (10) finally achieving a nice result, indicated by even and complete stent coverage of all the lesion segments and the vessel carina without stent deformation and abnormally shifting of the carina.
ECG and cardiac biomarkers
An 18-lead ECG was obtained before and 12 to 18 hours post-procedurally. CK-MB, cTnT/cTnI were measured at the time of the procedure and after 12 to 18 hours. CK-MB was used as the primary marker and cTnT/cTnI only if CK-MB was unavailable. To avoid confounding non-procedure-related marker elevation, patients with unstable angina pectoris were included in biomarker analysis only if preprocedure and postprocedure markers were normal. Marker elevation of 3 times the upper limit of normal was considered significant.
Coronary angiography (CAG) and intravascular ultrasound (IVUS)
CAG was performed at baseline, at completion of the procedure, and at the scheduled follow-up. IVUS examination was at the discretion of the operator pre-procedurally and at follow-up, but mandatory at completion of the procedure using a pull-back device starting at the point at least 5 mm distal to the end of stented segments of both branches and proximal to the stented end of the parent vessel.
Quantitative coronary angiographic (QCA) measurements of CBLs were obtained in 3 segments: the proximal PV segment, the distal segments of both branches. In the PV and MB segments, measurements were obtained in the stent and in the margins 5 mm proximal and distal to the stent (proximal or distal edge). In the SB, the stented segment and the 5 mm distal to the stent (distal edge) were assessed. For controlling variation, all measurements were conducted twice at a 2-week interval by two experienced observers, blinded to each other and to the results of the first measurements, and averaged.
PCI success definitions
PCI success was defined according to current American College of Cardiology/American Heart Association (ACC/AHA) PCI guideline.
A minimal stenosis diameter reduction to <20% together with grade 3 TIMI flow after the procedure was considered as an angiographic (anatomic) success.
An angiographic success without in-hospital major clinical complications e.g., death, myocardial infarction (MI), emergency revascularization, was defined as a procedural success.
In the short-term, a clinically successful PCI includes anatomic and procedural success with relief of signs and/or symptoms of myocardial ischemia after the procedure. The mid- or long-term clinical success requires that the short-term clinical success remains durable and that the patient has persistent relief of signs and symptoms of myocardial ischemia for more than 6 months after the procedure.
Non-Q-wave myocardial infarction (NQWMI) was defined as a CK-MB or cTnT/cTnI increase to ≥3 times the upper limit of normal range combined with clinical signs of MI, without new onset of pathological Q waves. Q-wave myocardial infarction (QWMI) was defined as new development of pathological Q waves in 2 contiguous leads together with clinical signs of MI (chest pain or increase in myocardial injury markers). Target lesion/vessel revascularization (TLR/TVR) was the repeat target lesion/vessel therapy either by PCI or by surgery. In-stent thrombosis (IST) was diagnosed according to the Academic Research Consortium (ARC) definition. Acute, subacute, or late thrombosis was defined as occurring within 24 hours, within 1 month, or during the succeeding 5 months after stent implantation, respectively.
Percent diameter stenosis (PDS) was calculated as (reference diameter-minimal luminal diameter) / reference diameter × 100. Defined binary stenosis (DBS) of >50% was considered significant. Minimal lumen diameter (MLD) was assessed on a projection of best viewing a lesion. Late lumen loss (LLL) was defined as post-procedure MLD minus MLD at 9-month follow-up.
For detailed document of the major adverse cardiac events (MACEs) including cardiac death, QW/NQWMI, TVR/TLR, and IST, all patients were asked for an index clinical follow-up visit at 1-, 3-, 6- and 9-month after discharge. A 9-month control CAG was indexed per protocol.
All analyses were performed with SPSS 13.0 (SPSS Inc., Chicago, USA). Discrete or categorical variables are presented as numbers (percentages), continuous variables as mean ± standard deviation (SD). To compare differences of the variables between each follow-up visit, the chi-square test or Fisher's exact test was employed for the discrete variables, and one way analysis of variance (ANOVA) for the continuous variables, followed by the paired t test. All probability values were 2-sided. The level of significance was 5%.
Baseline demographic and clinical characteristics of the patients
Baseline patient characteristics are listed in Table 1. A total of 33 patients with CBL underwent PCI with MCS, among whom 28 were male and 5 were female, aged (64.7±13.2) (51–81) years. Patients received PCI due to stable angina in 15%, unstable angina in 58%, NSTEMI in 21%, and STEMI in 6%.
Baseline angiographic and procedural characteristics
Baseline angiographic and procedural characteristics are shown in Table 2, Table 3. The target bifurcation lesion was located at LM/LAD/LCX in 8 (24%) patients, LAD/DB in 17 (52%) patients, LCX/OM in 3 (9%) patients, and RCA/PDA/PLA in 5 (15%) patients. In addition to treating the target bifurcation lesions, 5 patients had other coronary stenosis stented during the same intervention. According to ACC/AHA classification of lesion complexity, the treated target segments including 32 (97%) type B2/C lesions, 3 (9%) chronic total occlusions, 12 (36%) calcified lesions, 11 (33%) proximal and/or distal tortuous lesions. Moreover, defined according to Lefevre-Medina classifications (1,1,1), (1,0,1) or (0,1,1), 31 (94%) lesions represented a “true bifurcation” lesion morphology (Table 3). Accordingly, the treated lesions in the cohort of patients did represent really complex bifurcation lesions.
The procedural data are listed in Table 2 and Table 4. The angiographic or procedural success was achieved in 33/34 (97%) lesions by MCS (per MCS), one lesion was switched to receive DKS treatment by inflating the pre-imbedded balloon in a branch to crush the first deployed stent in another branch because of temporally acute closure and failed rewire of the branch following the first stent implantation. All the lesions underwent a successful FBK, and 12 (36%) lesions had to use non-compliance balloon for FBK due to residual stenosis (Table 2).
There were no peri-procedural death, MI (not clinically or biomarker defined MI), TLR/TVR and acute IST, resulting in the final procedural or angiographic success of 100% per protocol (Table 4).
The immediate QCA measurements are listed in Table 5. There was not significant residual in-stent stenosis, only with in-stent PDS (5.91±5.39)% in the PV, (8.30±5.34)% in the MB and (12.22±4.00)% in the SB. The post-procedural IVUS showed that incomplete stent expansion was found in 12 (36%) lesions before and no lesions after FBK using non-compliance balloons (P <0.05), and that stent mal-apposition not found post-procedurally after FBK.
There were no death, MI (not clinically or biomarker defined MI), TLR/TVR and sub-acute or late IST, only 2 patients had reoccurrence of angina with the grade of CCS I and CCS II each in one, resulting in the 9-month clinical success of 94% per MCS and 94% per protocol (Table 4).
The immediate and 9-month follow-up QCA measurements are listed in Table 5. As compared to the immediate QCA measurements, MLDs of the PV, the MB and the SB were significantly reduced with LLL of (0.10±0.14) mm, (0.21±0.23) mm and (0.27±0.32) mm, respectively. However, DBS was found only at 3 sites out of 2 patients, two located at the SB ostia (in-stent restenosis), one at stent distal margin (in-segment restenosis), with no patients undergoing TLR or TVR.
In the present pilot study, we first developed the MCS to treat bifurcation lesions that required dual-stent implantation. Our initial dada showed that MCS for the treatment of complex CBLs did have advantages over the various crushing techniques or conventional culotte stenting: much easier and safer to perform the operation, more readily to complete final balloon kissing, higher immediate technical success and optimal 9-month outcomes.
Comparison with previous bifurcation approaches
The optimal treatment strategy for CBLs remains to be defined. Recent studies support a strategy of provisional side branch stenting when confronted with the requirement for the CBL intervention.4–12 However, there is agreement among many interventional cardiologists that in several situations (e.g. severe SB ostial disease, dissection or diminished TIMI flow, a large territory at risk in SB, etc.) there is need for safer and more reliable double-stenting techniques.10–13 In this regard, different technical options are available to operators. The T-stenting is limited by a need for extremely precise stent positioning to ensure complete coverage of SB ostium. The alternative techniques, classic crush stenting or its modifications such as mini-crush, step-crush or DK crush, are relatively easy to perform, but FBK, which is mandatory to achieve acceptable rates of SB restenosis, is not always readily to be successfully completed particularly in using classic crush techniques.13
The conventional culotte stenting has several major advantages.13,19 First, it allows the operator to start the intervention using a provisional side branch stenting approach, also offers the advantage over the crush technique of having only two not three stent layers in the PV wall of a CBL, potentially leading to a lower risk of incomplete stent apposition. From a technical point of view, final re-wiring into the side branch, with the aim of performing FBK, is easier after culotte than after crush stenting techniques. Finally, the result after properly performed culotte stenting and FBK leads to optimal bifurcation coverage, least recoil at the ostial site, least residual stenosis, and less stent distortion in comparison with other techniques. These considerations are supported by the work of Ormiston et al22 in a bench testing model of coronary bifurcation interventions. Nevertheless, this dual-stenting technique, though first described one decade ago before the advent of DES, was not widely used clinically. Of course, only few clinical data were available in the literature until the outcomes of Nordic trial had been published.17–19,23
As compared to the conventional culotte stenting, MCS is characterized by its outstanding safety and reliability since the pre-imbedded balloon in the latter stented branch (usually the MB) totally avoided the possibility of the acute vessel closure. Accordingly, the operators, who are even inexperienced, are able to complete the procedure with confidence and without hesitation.
Technical considerations and procedural key points
Selection of open-cell-designed stent is essential to allow full stent expansion at the branch ostia. Pre-imbedding a balloon in the MB is crucial for preventing acute vessel closure and also providing the possibility for quickly switching to other crushing techniques in case of inability to rewire already closed or almost closed MB. Stenting the SB always goes first with stent protrusion of 1–2 mm into the MB, the initial inflating pressure should be lower just for appropriately expanding the stent distal end, followed by a high pressure inflation after withdrawing the stent balloon a little bit (0.5–1.0 mm), which ensures full dilation of the SB ostium and good apposition of the distal and proximal stent segment against the vessel wall. Remove the pre-imbedded balloon out of the MB after confirmation of successfully rewiring the MB true lumen while keeping the jailed wire until a balloon (the pre-imbedded balloon) has already passed the stent side-hole; alternatively, wire the MB prior to high pressure dilatation of the SB stent for preventing the MB occlusion. This step is really important since it can effectively avoid acute MB closure particularly in case of a true bifurcation lesion with severe ostial stenosis and also allows switching to crush techniques easily if unable to wire the MB or acute MB compromise due to the SB stent squeezing and/or plaque shifting, dissection or rupture. And finally, for a high quality procedure, it is necessary to wire or rewire both branches via the stent central side-hole against the ostia, and to perform a FBK with recommended use of non-compliance balloon.
The data in the present study demonstrated that the MCS did yield excellent immediate and 9-month angiographic and clinical outcomes. The immediate angiographic or procedural success was achieved in 34/34 (100%) lesions per protocol, 33/34 (97%) lesions per MCS with 100% FBK. Only 2 patients had reoccurrence of mild or moderate but controllable angina at 9-month follow-up, resulting in long-term clinical success of 94% per MCS and 94% per protocol.
In treatment of complex CBL with dual-stent strategy, the major concern has been the increased incidence of procedure-related biomarker elevation, IST and restenosis particularly at SB ostial site.16,17,24,25 In the present study, there were no procedure-related biomarker elevation and IST peri-procedurally and at 9 months follow-up. In-stent or in-segment DBS was infrequent with no patients undergoing TLR or TVR.
In terms of anti-restenosis, LLL and DBS rates in MB and SB particularly the latter were considered as main criteria for the assessment of long-term efficacy of CBL interventions.13,19,26 As compared to the immediate measurements, QCA data at 9 months showed that MLD of PV, MB and SB were significantly reduced with LLL of (0.10±0.14) mm, (0.21±0.23) mm and (0.27±0.32) mm, respectively. However, LLL was relatively low and acceptable especially for SB ostium, and in-stent or in-segment DBS was rare with no patients undergoing TLR or TVR.
For the technical point, when there was a “huge” size difference (1.5 mm) between the branches, the later implanted MV stent might not be well expanded; to overcome this limitation, an open-cell-designed stent for the SB was recommended and high pressure dilation of the proximal end of SB stent was necessary.
Although the present study demonstrated that MCS for treatment of CBLs was technically feasible and reliable, with good 9-month clinical and angiographic outcomes, the data were only from a pilot, relatively short-term observational study. The long-term efficacy warranted to be validated by a controlled, randomized, larger population study.
In conclusion, the present study demonstrated that MCS for treatment of CBLs that required dual-stent implantation was technically easy and safe, readily to complete FBK, and was associated with high immediate success and optimal 9-month outcomes.
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Keywords:© 2011 Chinese Medical Association
bifurcation lesion; stent; angioplasty; restenosis; follow-up study