Impact on Clinical Outcomes of Predilatation Using the Kissing-Balloon Technique for Crossover Stenting in True Coronary Bifurcation Lesions

Abstract: Background. Provisional crossover stenting has the potential risk of side-branch (SB) compromise, which may result in periprocedural myocardial infarction. Predilatation is a useful technique to prevent SB compromise. Objectives. The aim of this study was to assess the safety and efficacy of predilatation using the kissing-balloon technique (preKBT) during provisional crossover stenting compared with sequential predilatation on clinical outcomes in true coronary bifurcation lesions. Methods. We retrospectively evaluated 204 consecutive non-left main true bifurcation lesions (182 patients) in whom provisional crossover stenting was performed with preKBT (preKBT group, n = 144) or sequential predilatation (sequential group, n = 60) from March 2006 to February 2012. Results. There were 30 lesions (20.8%) in the preKBT group that developed SB ostial dissection compared with 8 lesions (13.3%) in the sequential group (P=.241). There was no SB flow impairment or SB access failure due to SB ostial dissection. SB compromise (Thrombolysis in Myocardial Infarction <3) immediately after crossover stenting occurred in 5 lesions (3.5%) in the preKBT group versus 7 lesions (11.7%) in the sequential group (P=.043). Major adverse cardiac events at 6-8 months of follow-up were observed in 5 lesions (3.5%) in the preKBT group versus 8 lesions (13.3%) in the sequential group (P=.022). Conclusions. Regardless of more complex bifurcation lesions in the preKBT group, preKBT successfully prevented SB compromise due to crossover stenting without unfavorable complications and improved the mid-term clinical outcome compared with sequential PTCA in patients with non-left main, true coronary bifurcation lesions.

J INVASIVE CARDIOL 2013;25(10):512-518

Key words: bifurcation, kissing balloon technique, predilatation

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Provisional crossover stenting has been commonly accepted as the gold standard in the field of percutaneous coronary intervention (PCI) for bifurcation lesions.^1-3 However, provisional main-vessel (MV) crossover stenting has a potential risk of side-branch (SB) compromise (Thrombolysis in Myocardial Infarction [TIMI] flow grade <3), which might increase the risk of periprocedural myocardial infarction (MI). In order to prevent SB compromise, the jailed-wire technique (JWT)⁴ was introduced, and various types of pretreatment techniques have been used, such as predilatation with the sequential technique or kissing-balloon technique (KBT),⁵ or directional coronary atherectomy and rotational atherectomy. Regardless of the use of these techniques, 5%-32% rates of SB compromise after MV crossover stenting have been reported.^4,6-11

In a recent study, the major mechanism of SB compromise after crossover stenting was thought to be carina shift.^12,13 Highly experienced operators prefer to perform the predilatation using the KBT (preKBT) because of less carina shift when there is a high probability of SB occlusion after crossover stenting. After introduction of preKBT, we seldom observed SB occlusion and it is common that two stents are not necessary regardless of complex true bifurcation lesions (Medina classification 1,1,1) or a small minimum lumen diameter (MLD) of the SB ostium, which has been reported to predict SB compromise^11,14-17 However, preKBT is not commonly accepted as a standard treatment. The recent paper also does not recommend preKBT because of the risk of extensive dissection;³ however, the efficacy and safety of preKBT for provisional crossover stenting in complex bifurcation lesions has not yet been fully investigated in the drug-eluting stent (DES) era. Therefore, in this study, we retrospectively compared the incidence of SB compromise immediately after MV crossover stenting and early and late clinical outcomes between preKBT and predilatation using the sequential technique in patients with non-left main true bifurcation lesions undergoing provisional crossover stenting. 

Methods

Study population. A total of 1150 consecutive bifurcation lesions were treated with provisional crossover stenting at Kusatsu Heart Center between March 2006 and February 2012. A bifurcation lesion was defined as narrowing of a coronary artery involving the origin of the SB. The flow diagram for inclusion and exclusion in the present study is shown in Figure 1. Target lesions that satisfied the following criteria (n = 946) were excluded: (1) left main disease; (2) restenosis lesion; (3) chronic total occlusion; (4) acute myocardial infarction; (5) reference diameter (RD) of the MV <2.3 mm or SB <1.5 mm measured by quantitative coronary angiography (QCA); (6) TIMI flow grade <3 in the MV or SB; (7) no predilatation of the SB; or (8) absence of true bifurcation lesions (Medina classification of 1,1,0; 1,0,0; 0,1,0; or 0,0,1). A true bifurcation lesion is defined as one with >50% diameter stenosis of the SB ostium by visual estimation (Medina classification of 1,1,1; 1,0,1; or 0,1,1).¹⁷ The final study population consisted of 182 patients that had 204 de novo bifurcation lesions treated with provisional crossover stenting. Of the 204 lesions, a total of 144 were predilated by KBT (preKBT group) and 60 were predilated by sequential technique (sequential group). All patients gave written informed consent before PCI, and follow-up angiography was scheduled at 6-8 months if needed. 

Stenting procedure. PCI was performed with an 8 Fr system via the femoral artery in the majority of cases. Baseline angiography and intravascular ultrasound (IVUS) were routinely performed prior to intervention. Two guidewires were placed in both branches. If the target lesion had multiple SBs, the most jeopardized or the largest SB was protected based on the angiography or IVUS findings. Predilatation of the MV was mandatory, but the choice of preKBT or sequential PTCA for predilatation of the SB was left to the operator’s discretion. The operator performed preKBT when there was a high probability of SB occlusion after MV crossover stenting. PreKBT was performed with two undersized balloons (2.5 mm for the MV and 2.0 mm for the SB in most of the lesions) using a Y-connector, and sequential predilatation was performed with one undersized balloon (2.25 mm for both branches in most of the lesions). Sequential inflation for each branch was performed followed by simultaneous balloon inflation in a KBT manner. MV predilatation followed by SB predilatation was performed in a sequential manner. Predilatation was performed with low pressure (6-8 atm) using compliant balloon for SB or the lesions that consisted of soft plaque, but with high pressure (>10 atm) using non-compliant balloon for the lesions that were calcified based on IVUS findings. IVUS was performed following predilatation to identify how the lesion expanded and to determine the extent of dissection. MV stenting was performed to cover the origin of the SB using the JWT. The SB was rewired through the MV stent struts when necessary. The position of the re-crossing guidewire at the SB ostium was confirmed by IVUS before final KBT in cases with a large SB. Final KBT was performed with the stent balloon (or larger-sized non-compliant balloon) for the MV and the same-sized balloon for the SB with a pressure of 8-12 atm. Bailout stenting (culotte stenting) was performed when necessary, even after repeated long inflation with KBT. IVUS was performed at the end of the entire procedure. Selection of the access site, guiding catheter, guidewire, stent type and size, and balloon size and inflation pressure were based on the operator’s preference.

Antiplatelet and anticoagulant therapy. Most patients received aspirin (100 mg/day) and clopidogrel (75 mg/day) before admission, if possible. Aspirin (100 mg) and a clopidogrel loading dose of 300 mg were administered immediately after the procedure if needed. A bolus of 8000 U of heparin was injected via the arterial sheath before the procedure, and the activated clotting time (ACT) was measured from blood taken via the guiding catheter. An additional bolus of 1000-3000 U was injected intravenously to maintain the ACT >300 seconds during the procedure.

Angiographic analysis. QCA was performed by an experienced technician who was blinded to the study objectives, using a standard edge-detection system (QAngioXA 7.3; Medis). MLD within the stent, RD, or percent diameter stenosis (%DS) of the MV and the SB were measured before stenting, after stenting, and at follow-up. 

Endpoints and definitions. The incidence of SB ostial dissection immediately after predilatation was evaluated using the National Heart, Lung, and Blood Institute criteria.¹⁸ The TIMI flow grade of the jailed SB during the procedure was evaluated at the time of, or immediately after, MV crossover stenting and final angiography. SB compromise was defined as a TIMI flow grade <3, and SB occlusion was defined as a TIMI flow grade of 0 or 1. SB accessibility was evaluated after attempted re-wiring to the SB through the MV stent struts. 

Angiographic success was defined as a TIMI flow grade of 3 in both branches with <30% residual stenosis of the MV. The procedure was considered clinically successful if there were no major adverse cardiac events (MACEs) during the hospital stay. MACEs were defined as cardiac death, myocardial infarction, or target lesion revascularization (TLR).¹⁹Myocardial infarction was defined as an elevation of CK levels more than 3 times the upper limit of normal at 12-18 hours after PCI and was evaluated after the treatment of each lesion.²⁰Target lesion revascularization was defined as revascularization driven by >70% diameter stenosis by visual estimation within the treated segment. Restenosis was defined as recurrent diameter stenosis >50% by QCA at follow-up. Clinical follow-up was obtained from review of medical records and/or telephone interviews. 

Statistical analysis. Continuous variables were expressed as the mean ± standard deviation and compared using a Student’s t-test. Categorical variables were expressed as rates or proportions and compared using a Fisher’s exact test. All analyses were performed using JMP version 10.0 software (SAS Institute, Inc). All P-values were two-sided, and P<.05 was considered statistically significant.

Results

Baseline clinical and angiographic features. Baseline clinical and procedural information were collected from the database of Kusatsu Heart Center. There were no significant differences between the two groups in baseline clinical characteristics (Table 1). Diabetes mellitus was present in more than half of the population. There were also no significant differences between the two groups in baseline angiographic characteristics (Table 2). Two-thirds of the bifurcated lesions had a Medina classification of 1,1,1 and left anterior descending coronary artery/diagonal bifurcations. The angiographic analyses of the index procedures are summarized in Table 3. There were no significant differences in the preprocedural QCA parameters between the two groups, except there was a trend for a higher %DS of both branches and a slightly longer MV lesion length in the preKBT group. 

Procedural results. Procedural details are described in Table 4. PCI for complex bifurcation lesions treated using a DES delivered through an 8 Fr guiding catheter in the femoral artery were common. IVUS examination was routinely performed in all patients. The average diameter of the predilatation balloon used for SB in the preKBT group was significantly smaller than that in the sequential group. DESs were implanted in more than 90% of the lesions, and a significantly larger number of the first-generation DES was used in the sequential group versus the preKBT group. There were no significant differences between the two groups in average diameter, average length, average deployment pressure, or the number of MV stents used. There were also no significant differences between the two groups in fluoroscopy dose, fluoroscopy time, or the volume of contrast media injected.

The details of the procedural results are shown in Table 5. Angiographic success was achieved in most cases. The frequency of SB ostial dissection (National Heart, Lung, and Blood Institute dissection types B-D) was not significantly different between the two groups, but slightly higher in the preKBT group. The rate of SB compromise (TIMI <3) immediately after MV stenting in the preKBT group was significantly lower than in the sequential group. The rate of SB occlusion (TIMI 0 or 1) immediately after MV stenting tended to be lower in the preKBT group. None of the lesions in the preKBT group developed SB occlusion at the end of the procedure. Re-crossing failure to the SB through the MV stent strut was rare in this study. Additional SB stenting was required less frequently in the preKBT group compared with the sequential group. Final KBT was performed in 82% of the bifurcated lesions. In-hospital clinical events are described in Table 6. Clinical success was achieved in the majority of lesions. There was no evidence of cardiac death. There were no significant differences in the incidence of periprocedural myocardial infarction. Postprocedure QCA analysis revealed that the MLD of the MV in the preKBT group was significantly larger than in the sequential group (Table 3). Complete angiographic data at follow-up were available for 75% of the lesions. The results of QCA at follow-up are shown in Table 7. The significant superiority in MLD of the MV was maintained at follow-up. Clinical follow-up data were available for all lesions. The incidences of MACE at 6-8 months of follow-up are shown in Table 7. The preKBT group had a lower rate of in-stent restenosis and a lower rate of TLR. The MACE rate in the preKBT group was significantly lower than in the sequential group. 

Discussion

The major findings of this retrospective study are: regardless of more complex bifurcation lesions in the preKBT group, (1) preKBT significantly reduced the incidence of SB compromise following MV crossover stenting; (2) MV proximal dissection or SB ostial dissection caused by preKBT did not increase stent length, the number of stents deployed, SB compromise, or SB access failure; and (3) preKBT significantly reduced MACE rates during follow-up (largely driven by a lower TLR rate) in comparison with sequential percutaneous transluminal coronary angioplasty in non-left main true bifurcation coronary lesions treated with provisional stenting. 

Effect of preKBT on side-branch compromise or periprocedural myocardial infarction. We previously performed preKBT or DCA for crossover stenting to reduce the risk of plaque and/or carina shift due to stent expansion.^21,22 Bruech et al showed that preKBT successfully reduced the rate of transient SB compromise following MV stenting compared with sequential predilatation (0% vs 33%; P=.003), but preKBT failed to reduce the rate of periprocedural myocardial infarction in their small bare-metal stent series (n = 59).²³ Consistent with Bruech et al, our results revealed that preKBT significantly reduced the rate of SB compromise after MV crossover stenting compared with sequential PTCA (3.5% vs 11.7%; P=.043), but preKBT did not reduce periprocedural myocardial infarction (2.8% vs 3.3%; P=1.000). It is noteworthy that the incidence of the SB flow impairment after MV crossover stenting in the preKBT group was very low, despite the fact that the preKBT group had more complex true bifurcation lesions, including 67.7% with a Medina classification of 1,1,1 and a smaller MLD of the SB, which has been reported to predict SB compromise.^15,24,25 Altogether, the incidence of SB compromise and stenting was very low in both groups.

Effect of dissection created by predilatation on clinical outcome. It is still controversial whether preKBT is safe and effective in improving clinical outcomes. In a recent paper, preKBT was not recommended due to the following risks: (1) extensive dissection; (2) occurrence of dissection at the SB ostium that hinders access to the SB; and (3) enlargement of the SB lumen with an increased chance of re-crossing through a proximal strut that interferes with scaffolding of the SB ostium by the protruded strut.³ An additional concern is whether dissection at the SB ostium would impair SB flow. However, the present study showed the following results: (1) preKBT did not increase the number of stents deployed or stent length for covering extended dissection in both the MV and SB; (2) the lesions with SB ostial dissection did not hinder access to the SB; and (3) enlargement of the SB ostium did not increase the chance of re-crossing through a proximal strut, but did increase the chance of re-crossing through a distal strut that facilitated scaffolding of the SB ostium by the protruded strut. Furthermore, the occurrence of dissection at the SB ostium did not impair SB flow. In order to avoid extensive dissection, predilatation was performed carefully with minimum pressure, and IVUS was performed immediately after re-wiring to the SB to confirm whether or not the crossing strut was the most distal strut in the stent. These meticulous procedures may have prevented extensive dissection and increased the chance of covering the ostial dissection by the protruded strut. Surprisingly, there was no bailout stenting required for the SB in the preKBT group, regardless of more complex true bifurcation lesions in this group. 

Effect of preKBT on major adverse cardiac events at follow-up. In spite of higher morbidity due to diabetes mellitus, B2/C lesions and multivessel disease in the preKBT group, there was a very low incidence of MACE at follow-up. It should be emphasized that SB ostial dissection rarely induced restenosis and the maintenance of the MLD of the MV in the preKBT group likely contributed to a lower rate of restenosis and TLR.

Possible beneficial mechanisms of preKBT. We propose the following possible beneficial effects of preKBT: (1) simultaneous balloon inflation proximal to the carina contributes to the full expansion of the proximal MV stent (occasionally with enlargement of the SB ostium proximal to carina); (2) balloon inflation distal to the carina with reduced carina displacement contributes to full expansion of the distal stent; and (3) vessel dilatation at the SB ostium with reduced carina displacement creates enough space to secure SB flow by canceling the carina shift due to MV stenting. Consequently, enlargement of the SB ostium can secure the SB flow and prevent ischemic symptoms during crossover stenting. It allows enough time for re-wiring of the SB through the most distal strut with avoidance of SB ostial dissection at the proximal strut. However, enlargement of the SB ostium due to less carina shift might induce more frequent SB ostial dissection, despite a smaller balloon used in the preKBT group. On the other hand, the sequential technique seemed to be unable to prevent carina shift, resulting in less expansion of both lesions distal to the carina and the ostium of the SB. 

The results of this study suggested that preKBT might have a more powerful effect on stent expansion than the final KBT, because some differences could be seen between the two groups in spite of a high success rate of the final KBT in both groups. Although preKBT may seem to be technically demanding and time consuming, there was no increase in contrast volume, fluoroscopy time, or fluoroscopy dose in the preKBT group. Finally, it should be emphasized that these findings were novel because there were very few data about preKBT; the following new insights could be obtained from these findings: (1) lesion preparation might be more important than how the lesion is treated after stenting; (2) preKBT may obviate the need for final KBT or SB stenting; and (3) preKBT may make procedures simple and safe in cases of complex bifurcation lesions. 

Study limitations. Our study has the following limitations. It was a non-randomized, retrospective study performed at a single center. The preKBT group had the most complicated bifurcation lesions compared with the sequential group, because the decision to perform preKBT or sequential predilatation was left to the operator’s discretion. Actually, the MLD of the SB had a tendency to be smaller in the preKBT group than in the sequential group. Thus, patient selection bias was likely, and this may have negated the advantage of preKBT. Propensity matching was not used to try to create two similar groups. The small number of patients limited the event rates and reduced the statistical power of the study to detect a difference in clinical outcomes between the two strategies. In addition, angiographic follow-up was limited in 75% of the population. Therefore, we did not evaluate the independent predictors of a poor clinical outcome using logistic regression analysis. QCA analysis was not performed by a core laboratory. A smaller balloon was used for the SB and a medium one for the MV in the preKBT group, whereas only one medium-sized balloon was used for both the MV and SB in the sequential predilatation group to reduce the cost of the procedure. The percent use of the first-generation DES was higher in the sequential group. These differences could have affected the procedural results. Furthermore, there was a learning curve during the study period that could also have influenced the results. A randomized, multicenter study in a larger population will be required to confirm the beneficial effects of preKBT.  

Conclusions

Regardless of more complex bifurcation lesions in the preKBT group, preKBT could safely prevent SB compromise following MV crossover stenting. Although SB ostial dissection was more frequent in the preKBT group, it did not interfere with SB access, impair SB flow, or increase the need for bailout stenting. PreKBT improved the rate of in-stent restenosis, TLR, and MACE at 6-8 months of follow-up compared with sequential percutaneous transluminal coronary angioplasty in non-left main true bifurcation lesions treated with provisional stenting. Conventional KBT is still an effective and safe pretreatment method for provisional crossover stenting with complex bifurcation PCI. Further randomized studies will be required to clarify the effectiveness of preKBT on clinical outcomes.

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