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Original article
Final kissing ballooning and long-term clinical outcomes in coronary bifurcation lesions treated with 1-stent technique: results from the COBIS registry
  1. Hyeon-Cheol Gwon1,
  2. Joo-Yong Hahn1,
  3. Bon-Kwon Koo2,
  4. Young Bin Song1,
  5. Seung-Hyuk Choi1,
  6. Jin-Ho Choi1,
  7. Sang Hoon Lee1,
  8. Myung-Ho Jeong3,
  9. Hyo-Soo Kim2,
  10. In-Whan Seong4,
  11. Ju-Young Yang5,
  12. Seung Woon Rha6,
  13. Yangsoo Jang7,
  14. Jung Han Yoon8,
  15. Seung-Jea Tahk9,
  16. Ki Bae Seung10,
  17. Seung-Jung Park11
  1. 1Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  2. 2Seoul National University Hospital, Seoul, Korea
  3. 3Chonnam National University Hospital, Gwangju, Korea
  4. 4Chungnam National University Hospital, Daejeon, Korea
  5. 5Nation Health Insurance Corporation, Ilsan Hospital, Goyang, Korea
  6. 6Korea University Guro Hospital, Seoul, Korea
  7. 7Yonsei University Severance Hospital, Seoul, Korea
  8. 8Yonsei University Wonju College of Medicine, Wonju, Korea
  9. 9Ajou University Hospital, Suwon, Korea
  10. 10Catholic University Seoul St. Mary's Hospital, Seoul, Korea
  11. 11Ulsan University Asan Medical Center, Seoul, Korea
  1. Correspondence to Professor Dr Hyeon-Cheol Gwon, Cardiac and Vascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea; hcgwon{at}skku.edu

Abstract

Background Whether final kissing ballooning (FKB) is mandatory in the 1-stent technique is uncertain.

Objective To evaluate the effect of FKB on long-term clinical outcomes in coronary bifurcation lesions treated with the 1-stent technique.

Methods Consecutive patients undergoing percutaneous coronary intervention using drug-eluting stents for non-left main bifurcation lesions were enrolled from 16 centres in Korea between January 2004 and June 2006. In patients treated with the 1-stent technique major adverse cardiac events (MACE; cardiac death, myocardial infarction (MI), or target lesion revascularisation (TLR)) were compared between those undergoing main vessel stenting only (non-FKB group, n=736) or those undergoing FKB after main vessel stenting (FKB group, n=329). Propensity score-matching analysis was also performed in 222 patient pairs (444 from the non-FKB group and 222 from the FKB group).

Results During follow-up (median 22 months), the FKB group had a higher incidence of MACE (HR 2.58; 95% CI 1.52 to 4.37; p<0.001) and TLR (HR 3.63; 95% CI 2.00 to 6.56; p<0.001), but not of cardiac death or MI. Most TLR occurred in the main vessel (HR 3.39 for the FKB group; 95% CI 1.86 to 6.19; p<0.001). The rate of stent thrombosis was similar in both groups (0.5% in the non-FKB group vs 0.6% in the FKB group, p=0.99). After propensity score matching, the FKB group still had higher rates of MACE and TLR than the non-FKB group (HR 2.13; 95% CI 1.15 to 3.95; p=0.02 and HR 2.84; 95% CI 1.45 to 5.55; p=0.002, respectively).

Conclusions In patients treated with the 1-stent technique for bifurcation lesions, FKB after main vessel stenting may be harmful mainly due to increased TLR.

Trial Registration Number clinicaltrials.gov number: NCT00851526.

  • acute coronary syndrome
  • angioplasty
  • atherosclerosis
  • bifurcation lesions
  • chest pain clinic
  • coronary artery disease
  • coronary stenting
  • fractional flow reserve
  • interventional cardiology
  • intravascular ultrasound
  • kissing ballooning
  • molecular biology
  • MRI
  • myocardial ischaemia and infarction (IHD)
  • restenosis
  • spasm

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For coronary bifurcation lesions, the elective 2-stent technique has never been proved superior to the 1-stent approach, even in the current era of drug-eluting stents (DES).1–4 The provisional approach, a selective side branch (SB) intervention after main vessel stenting, is now regarded as the standard technique for most bifurcation lesions.5 However, whether final kissing ballooning (FKB) after main vessel stenting should be mandatory or can improve clinical outcomes in the 1-stent technique remains unclear as limited data are currently available.6 The aim of our study was to evaluate whether FKB after main vessel stenting affects long-term clinical outcomes in patients with coronary bifurcation lesions using a large, dedicated bifurcation registry.

Methods

Study population

The COronary BIfurcation Stent (COBIS) registry is a retrospective multicentre registry dedicated to bifurcation lesion percutaneous coronary intervention (PCI) with DES.7 In total, 1668 consecutive patients from 16 major coronary intervention centres in Korea were enrolled in this registry between January 2004 and June 2006, using the following inclusion criteria: coronary bifurcation lesions treated solely with DES; a main vessel diameter of 2.5 mm or greater, and a side branch diameter of 2.0 mm or greater. The exclusion criteria were: cardiogenic shock; ST-segment elevation acute myocardial infarction (MI) during the preceding 48 h; life expectancy less than 1 year; or left main bifurcation. This registry was sponsored by the Korean Society of Interventional Cardiology. The local institutional review board at each hospital approved this study and waived the requirement for informed consent on access to each institutional PCI registry.

To assess the effect of FKB after main vessel stenting on clinical outcomes in patients undergoing the provisional approach, we selected patients treated with the 1-stent technique in one bifurcation lesion in the COBIS registry database (n=1229). We confirmed whether FKB had been performed by review of the angiograms in all cases. Cases of bail-out side branch intervention for thrombolysis in MI flow less than three (n=55) or dissection of type B or worse (n=4) in the side branch after main vessel stenting were excluded. Bifurcation lesions treated with side branch ballooning, but not followed by FKB (n=92) or with angiograms of suboptimal quality for analysis were also excluded (n=13). Finally, 1065 patients who met the selection criteria were included in this analysis.

Percutaneous coronary intervention

All patients were prescribed aspirin (300 mg) and either clopidogrel (300–600 mg) or ticlopidine (500 mg) unless these antiplatelet medications had previously been administered. Anticoagulation during PCI was performed as per the current practice guidelines established by the Korean Society of Interventional Cardiology. The access, type of DES and use of intravascular ultrasound or glycoprotein IIb/IIIa receptor inhibitors were all left to the operator's discretion. Decisions to perform FKB were taken by the individual operators. Aspirin was continued indefinitely, and the duration of thienopyridine treatment was also at the operator's discretion.

Data collection and analysis

Clinical, angiographic, procedural and outcome data were collected using a web-based reporting system. Additional information was obtained through a review of the medical records or by telephone contact, if necessary. All baseline and procedural cine coronary angiograms were reviewed and analysed quantitatively at the angiographic core laboratory (Samsung Medical Center, Seoul, Korea) using standard definitions.8 Medina classification type (1.1.1), (1.0.1) and (0.1.1) lesions were defined as true bifurcation lesions.9 For quantitative coronary angiographic (QCA) analysis, bifurcation lesions were divided into eight segments: proximal reference; main vessel proximal (proximal to side branch take-off); main vessel middle (<5 mm distal to take-off); main vessel distal; main vessel distal reference; side branch ostial (<5 mm distal to take-off); side branch distal and side branch reference segments (figure 1). The minimum luminal diameters (MLD) before the procedure, after main vessel stenting but before FKB, if applicable, and after all the procedures were measured in matched views. For the main vessel, the reference diameter (RD) was the average of the proximal and distal reference lumen diameters. For the side branch, the RD was the distal reference lumen diameter. Diameter stenosis was calculated by 100×(RD−MLD)/RD.

Figure 1

Schematic diagram of quantitative coronary angiographic analysis: (1) Main vessel (MV) proximal reference diameter (RD); (2) main vessel distal RD; (3) side branch (SB) distal RD; (4) main vessel proximal (proximal to side branch take-off) minimum luminal diameter (MLD); (5) main vessel middle (<5 mm distal to take-off) MLD; (6) main vessel distal MLD; (7) side branch ostial (<5 mm distal to take-off) MLD; (8) side branch distal MLD; (9) main vessel lesion length; and 10) side branch lesion length.

Study outcomes and definitions

The primary outcome was the major adverse cardiac event (MACE) during follow-up, defined as a composite of cardiac death, MI, or target lesion revascularisation (TLR). Clinical events were defined based on the recommendations from the Academic Research Consortium.10 All deaths were considered cardiac unless a definite non-cardiac cause could be established. MI was defined as an elevation of creatine kinase MB fraction or troponin-T/troponin-I greater than the upper limit of normal with concomitant ischaemic symptoms or electrocardiography findings indicative of ischaemia. Periprocedural enzyme elevation was not included in this definition of MI. TLR was repeat PCI of the lesion within 5 mm of deployed stent or bypass graft surgery of the target vessel. Target vessel revascularisation was repeat revascularisation of the target vessel by PCI or bypass graft surgery. Definite, probable and possible stent thrombosis was also defined according to Academic Research Consortium recommendations.10 Stent thrombosis timing was classified as early (within 1 month after index procedure), late (between 1 month and 1 year) and very late (after 1 year). All events were confirmed by source documentation and reviewed by an independent clinical event adjudicated committee.

Statistical analysis

Analysis of continuous variables was performed using either the t test or the Wilcoxon rank-sum test. Categorical variables were analysed using the χ2 test or Fisher's exact test as appropriate. Survival curves were constructed using Kaplan–Meier methods and were compared using the log-rank test. The Cox proportional hazard model was used to identify independent predictors of MACE. The following variables were included for the Cox model: side branch ballooning after main vessel stenting, age, diabetes, acute coronary syndrome, stent type, true bifurcation, intravascular ultrasound guidance, the main vessel MLD after main vessel stenting (before FKB), the side branch MLD after main vessel stenting (before FKB) and lesion length of main vessel.

To reduce treatment selection bias for FKB and any other related potential confounding, we performed adjustment for the baseline characteristics of patients using propensity scores. The propensity scores were estimated using multiple logistic regression analysis. A full non-parsimonious model was developed that included all variables listed in tables 1 and 2, and baseline QCA data. In addition, we included QCA data immediately after main vessel stenting but before FKB in the model. In bifurcation lesions treated with main vessel stenting only, final QCA data were included. The discrimination and calibration abilities of this propensity score model were assessed by means of the c-statistic. Pairs were matched by an optimal balance based on a genetic algorithm. As the number of bifurcation lesions treated with FKB was much smaller than bifurcation lesions treated with main vessel stenting only, matching was performed with 1:2 manners. We assessed the balance in baseline covariates between the two groups in a propensity score-matched cohort through the standardised mean difference and hypothesis test using the stratified analyses considering matched pair (two-way analysis of variance or Friedman test) for continuous variables, and the Mantel–Haenszel method for categorical variables. In the propensity score-matched population, reductions in outcome risk were compared by a conditional Cox regression model.11 A two-sided p value of less than0.05 was considered statistically significant. All analyses were performed using a statistical analysis software package (SAS V. 9.1) and a matching package in R 2.11.

Table 1

Baseline patient characteristics

Table 2

Lesion and procedural characteristics

Results

Characteristics of study population

After main vessel stenting, the procedure was finished without any side branch intervention in 736 patients (69.1%, non-FKB group), while FKB was performed in 329 patients (30.9%, FKB group). Baseline characteristics of the two groups are shown in tables 1 and 2. Compared with the non-FKB group, the FKB group tended to have a higher prevalence of men, but a lower prevalence of acute MI, dyslipidaemia and chronic renal failure. Angiographic analysis showed that true bifurcation was noted more frequently in the FKB group than in the non-FKB group. The use of sirolimus-eluting stents and side branch predilation before main vessel stenting was performed more frequently in the FKB group than the non-FKB group.

QCA data

The RD was similar in the main vessel between the groups, while the RD of the side branch was significantly larger in the FKB group than the non-FKB group (table 3). The baseline MLD of the side branch was significantly smaller in the FKB group than in the non-FKB group. After main vessel stenting (before FKB), the side branch MLD as well as the main vessel middle MLD were significantly smaller in the FKB group than in the non-FKB group. After FKB, the main vessel proximal MLD and side branch ostial MLD were significantly larger in the FKB group, whereas no significant difference was observed in the main vessel middle MLD between groups.

Table 3

QCA data

Clinical outcomes

Complete follow-up data for MACE were obtained in 98.4% of the overall population. During follow-up (median 22 months, IQR 15–33 months), 69 MACE occurred. The incidence of MACE was significantly higher in the FKB group than in the non-FKB group (table 4 and figure 2A), mainly driven by a higher TLR rate. In particular, most TLR were observed to occur in the main vessel. However, rates of cardiac death and MI were not significantly different between the two groups. In multivariate analysis, the FKB group was still found to have a significantly higher risk of MACE (HR 2.58; 95% CI 1.52 to 4.37; p<0.001) and TLR (HR 3.63; 95% CI 2.00 to 6.56; p<0.001). The definite or probable stent thrombosis rate was not significantly different between the groups (0.5% in the non-FKB group and 0.6% in the FKB group, p=0.42). Dual antiplatelet therapy was maintained in 88.6% and 62.5% of patients at 6 months and 1 year, respectively.

Table 4

Clinical outcomes

Figure 2

(A) Kaplan–Meier curves for major adverse cardiac events (MACE) in the overall population treated by main vessel stenting only (non-final kissing ballooning (FKB) group) versus FKB after main vessel stenting (FKB group). (B) Kaplan–Meier curves for MACE in propensity-matched patients.

Propensity score: matched analysis

After performing propensity score matching, a total of 222 matched pairs (444 patients from the non-FKB group and 222 patients from the FKB group) were generated. The c-statistic for the propensity score model was 0.83, indicating good discrimination. There were no significant differences in baseline clinical, lesion and procedural characteristics for the propensity-matched subjects except the type of bifurcations by Medina classification (tables 1 and 2). However, the frequency of true bifurcation was not significantly different between the groups. Although the baseline QCA data including the side branch ostial MLD were not significantly different between the two groups, the side branch ostial MLD after main vessel stenting (before FKB) was significantly smaller in the FKB group than in the non-FKB group. After FKB, the side branch ostial MLD became significantly larger in the FKB group than in the non-FKB group (table 3).

A total of 41 MACE occurred during a median follow-up of 22 months in the matched patients. The FKB group was associated with significantly worse outcomes than the non-FKB group in the matched cohort (table 4 and figure 2B). Although there were no significant differences in the incidence of cardiac death or MI between groups, patients in the FKB group had a significantly higher rate of TLR compared with those in the non-FKB group. In multivariate analysis using the side branch MLD before FKB as a covariate, the FKB group still showed a significantly higher incidence of MACE (HR 2.13; 95% CI 1.15 to 3.95; p=0.02) and TLR (HR 2.84; 95% CI 1.45 to 5.55; p=0.002). The definite or probable stent thrombosis rate was not significantly different between the groups (0.5% in the non-FKB group and 0.9% in the FKB group, p=0.60).

Subgroup analysis

The rate of MACE was consistently higher in the FKB group than in the non-FKB group across several subgroups (figure 3). However, there was a strong tendency for significant interaction between the presence or absence of true bifurcation lesions and MACE (p for interaction 0.052). While the MACE rate was not significantly different between the groups in non-true bifurcation lesions, the MACE rate was substantially higher in the FKB group than in the non-FKB group among patients with true bifurcation lesions.

Figure 3

Comparison of major adverse cardiac events for subgroups. ACS, acute coronary syndrome; FKB, final kissing ballooning; MV, main vessel; PES, paclitaxel-eluting stents; SB, side branch.

Discussion

In the present study, we investigated the effect of FKB after main vessel stenting on long-term clinical outcomes using a large dedicated bifurcation registry. FKB in the 1-stent technique increased the long-term risk of MACE, primarily as a result of an increased risk of TLR. However, no significant differences were observed in rates of cardiac death, MI, or stent thrombosis between groups.

Although the 1-stent technique or provisional approach is now prevailing for coronary bifurcation lesions,12 13 an optimal method has not been established. In cases in which decreased thrombolysis in MI flow or severe dissection do not occur in the side branch, the benefit of side branch ballooning or FKB in the provisional approach remains uncertain. The benefit of FKB is demonstrated only in bifurcation lesions treated with the 2-stent technique, mostly using the crush technique.3 14 Unfortunately, there has been a paucity of clinical data regarding FKB in the 1-stent technique. In the NORDIC–BALTIC Bifurcation Study III, the only relevant randomised study, routine kissing ballooning did not improve clinical outcomes in the 1-stent technique.6 However, in that particular study, only 20% of the eligible patients were enrolled, the sample size was not adequate to draw definite conclusions, the event rate was too low and the follow-up duration was only 6 months. Moreover, the frequency of true bifurcation was less than 50% and, surprisingly, the side branch MLD after the procedure was similar in the FKB group and the control group. Accordingly, we selected patients treated with the 1-stent technique in a multicentre registry dedicated to bifurcation lesions to investigate the effects of FKB in a real-world practice. The large number of patients and long-term follow-up duration strengthened our results. Propensity score-matched analysis was also performed to adjust differences in baseline characteristics between groups. We also performed QCA analysis step by step; before the procedure, after main vessel stenting but before FKB and after FKB.

Theoretically, FKB may provide scaffolding for the side branch ostium, preserve access to the side branch, or optimise stent architecture.15 However, in the present study, FKB increased the long-term risk of TLR, most of which occurred in the main vessel. Side branch ballooning or FKB may cause unfavourable effects on the main vessel. In an intravascular ultrasound study on bifurcation lesions treated with the 1-stent technique, the cross-sectional area of the main vessel stent immediately distal to the side branch origin was significantly reduced after side branch ballooning, which did not return to its initial value even after kissing ballooning.16 Decreased main vessel stent area associated with side branch intervention may translate into increased restenosis and TLR in the main vessel. While our results did not identify a difference in the postprocedural MLD of the main vessel between groups, QCA might have limitations in bifurcation lesions. Main vessel stent deformation or polymer disruption of DES caused by side branch ballooning or FKB may explain the increased TLR rate in the main vessel. FKB may cause injury in the main vessel proximal part due to overdilatation. On the other hand, side branch ballooning or FKB may affect local haemodynamic conditions. Recent computational fluid dynamics analysis demonstrated that there was no benefit to side branch intervention from a fluid dynamics perspective, and suggested that overdilatation of the main vessel proximal segment associated with FKB would result in additional flow disturbances.17 Moreover, our study showed that the larger side branch ostium MLD after the procedure in the FKB group did not yield favourable clinical outcomes, mainly because of the very low TLR rate of the side branch in both groups. Given that most jailed side branchs do not have physiological significance,18 FKB should be performed very selectively. As mentioned above, routine FKB did not improve angiographic outcomes in the NORDIC–BALTIC Bifurcation Study III. However, bail-out side branch intervention for decreased flow or significant dissection may be justified to reduce the risk of periprocedural myocardial injury, and was excluded in this analysis.

When compared with the non-FKB group, the FKB group had consistently worse outcomes across various subgroups regardless of true bifurcation, side branch size and residual stenosis in the side branch. Although there was a strong tendency for significant interaction between the presence or absence of true bifurcation lesions and MACE, this relationship probably resulted from similar MACE rates between the non-FKB group and the FKB group in patients with non-true bifurcation lesions. The MACE rate was much higher in the FKB group than in the non-FKB group among patients with true bifurcation lesions. As true bifurcation lesions are more advanced lesions than non-true bifurcation lesions, the implications of a suboptimal procedure may be greater in true bifurcation rather than in non-true bifurcation lesions. However, as these are the results of a post-hoc subgroup analysis, they should be interpreted carefully.

There are several limitations to our study. First, this study was not a randomised study, which may have significantly affected the results due to confounding factors. Several baseline characteristics were significantly different between groups, and the decision to perform FKB in each patient was made by the operator. Although we performed multivariable and propensity score-matched analyses to adjust for potential confounding factors, we were not able to control all variables. Second, as patients treated with the 2-stent technique were excluded, bifurcation lesions that may have benefited from side branch interventions were not included in our analysis.

Conclusions

We investigated the effect of FKB ballooning after main vessel stenting on long-term clinical outcomes using a large dedicated bifurcation registry. FKB increased the long-term risk of MACE, primarily due to increased TLR in the main vessel. Based on our results, routine FKB is not recommended in the 1-stent technique for coronary bifurcation lesions.

References

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Footnotes

  • See Editorial, p 175

  • The first two authors contributed equally to this work.

  • Funding This work was supported by the Korean Society of Interventional Cardiology, Seoul, Republic of Korea.

  • Competing interests None.

  • Ethics approval The local institutional review board at each hospital approved this study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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