Objective We evaluated differences in clinical outcomes between patients who underwent final kissing balloon inflation (FKBI) and patients who did not undergo FKBI in bifurcation treatment using the Tryton Side Branch Stent (Tryton Medical, Durham, North Carolina, USA).
Methods Clinical outcomes were defined as target vessel failure (composite of cardiac death, any myocardial infarction and clinically indicated target vessel revascularisation), cardiac death, myocardial infarction (MI), clinically indicated target vessel revascularisation and stent thrombosis. Cumulative event rates were estimated using the Kaplan-Meier method. A multivariable logistic regression analysis was performed to evaluate which factors were potentially associated with FKBI performance.
Results Follow-up data was available in 717 (96%) patients with a median follow-up of 190 days. Cardiac death at 1 year occurred more often in the no-FKBI group (1.7% vs 4.6%, respectively, p=0.017), although this difference was no longer observed after excluding patients presenting with ST segment elevation MI (1.6% vs 3.3%, p=0.133). No significant differences were observed concerning the other clinical outcomes. One-year target vessel failure rates were 10.1% in the no-FKBI group and 9.2% in the FKBI group (p=0.257). Multivariable logistic regression analysis identified renal dysfunction, ST segment elevation MI as percutaneous coronary intervention indication, narrow (<30°) bifurcation angle and certain stent platforms as being independently associated with unsuccessful FKBI.
Conclusions A lower cardiac death rate was observed in patients in whom FKBI was performed compared with a selection of patients in whom FKBI could not be performed, probably explained by an unbalance in the baseline risk profile of the patients. No differences were observed regarding the other clinical outcomes.
- Coronary Artery Disease
- Interventional Cardiology
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Coronary bifurcation lesions are frequently encountered in daily clinical practice by interventional cardiologists and account for 20% of all coronary lesions treated by percutaneous coronary intervention (PCI).1 ,2 Although clinical outcomes have been improved with drug-eluting stents (DES) in contemporary clinical practice,3 PCI of bifurcation lesions remains to be associated with an increased risk of instent restenosis (ISR) and stent thrombosis (ST).1 ,4
Therefore, several dedicated bifurcation stents, such as the Tryton Side Branch Stent (Tryton Medical, Durham, North Carolina, USA), have been developed to improve outcomes after coronary bifurcation stenting. Tryton is a side branch (SB) first stent, and is used in combination with a regular DES in the main branch (MB) and could be considered as a modified culotte technique.5 Previous smaller studies with the Tryton stent have shown promising procedural and clinical outcomes,6–9 which were confirmed by a recent patient pooled analysis including more than 900 patients.10
Besides dedicated stents, dedicated bifurcation treatment techniques have been developed to improve clinical outcomes. One of the most deeply investigated is the final kissing balloon inflation (FKBI) technique.11 In general, with the FKBI technique, two balloons are introduced over two separate guide wires: one balloon is positioned in the SB while the other is placed in the MB crossing the SB. The balloons are inflated simultaneously, opening the SB while preventing geometric distortions in the MB.11 Currently, there is consensus that FKBI is mandatory in complex two-stent bifurcation techniques,12 based on non-randomised studies evaluating the crush13–15 and culotte16 two-stent techniques. In bifurcation treatment using single-stent techniques however, FKBI did not show to improve clinical outcomes, as demonstrated by randomised trials comparing FKBI with no FKBI.17–19
Being a two-stent technique, it is recommended by the instructions for use to end a Tryton procedure with FKBI. However, FKBI is not performed in all cases in daily clinical practice,10 because fenestration of a guide wire through stent struts of the MB stent into the SB and subsequent advancement of a balloon can be technically challenging and time consuming, often at the cost of higher amount of contrast use and longer procedure and fluoroscopy time.19
Data on PCI with Tryton without FKBI is lacking and it is unclear whether patients in whom FKBI is not performed are at higher risk for the occurrence of clinical adverse events than patients in whom FKBI is successfully performed. Therefore, we evaluated clinical outcomes of patients who have been treated with Tryton with or without FKBI. Furthermore, we performed an analysis to explore which factors were associated with unsuccessful FKBI.
The current analysis was performed on patients included in the previous published patient-level pooled analysis of the Tryton stent.10 In this pooled analysis, Tryton Medical was contacted and a literature search was performed to identify registries investigating clinical performance of the Tryton stent. Ten registry studies were identified which included consecutive patients who had been treated with the Tryton stent. Investigators of eight registries agreed to participate in the pooled analysis and provided individual patient data on demographics, clinical history, risk factors for coronary artery disease, lesion and procedural characteristics as well as individual clinical outcomes. Datasets from these eight registries were sent for merging to the coordinating centre at the Academic Medical Center in Amsterdam. Each investigator vouched for the correctness of the data.
After receiving individual patient data, an assessment was performed to identify duplicates. Hereafter, datasets were merged to form one pooled patient database including 905 patients with 929 bifurcation lesions. Patients were included in the current study if information on FKBI performance was available. Patients from the IUVANT and Wolverhampton registries were excluded because they did not capture details on FKBI. Furthermore, patients in whom the Tryton stent was not successfully placed were also excluded (see figure 1).
The Tryton stent has been extensively described previously.5 In short, it is a 5 or 6 Fr-compatible balloon-expandable cobalt-chromium bare-metal stent (BMS). Its Tri-ZONE design allows SB scaffolding (distal zone), accommodation to a wide range of carinal anatomy (transition zone) and easy MB stent delivery due to a minimal amount of stent struts (proximal zone). Figure 2 shows the deployment sequence of the device.
For the current analyses, clinical outcomes were defined as: target vessel failure (TVF; composite of cardiac death, any myocardial infarction (MI) and clinically indicated target vessel revascularisation (TVR)), the composite of death and MI, cardiac death, any MI (including periprocedural and spontaneous MI), clinically indicated TVR, clinically indicated target lesion revascularisation (TLR) and ST (subdivided into definite and probable). Clinical outcome adjudication was in accordance with the definitions of the Academic Research Consortium.20 All data on clinical outcomes were site-reported. None of the included registries used an independant clinical endpoint committee to adjudicate the clinical end points. The First-In-Man, eTryton 150/Benelux, and eTryton Spain registries used similar online electronic case report forms to collect data on clinical outcomes, while the investigators of the Amsterdam, Poznan and Dublin registries provided their outcome data in Excel spreadsheets.
Continuous variables were reported as mean (±SD) or median (IQR), where appropriate. Categorical variables were presented as frequencies (%). Comparisons between groups were performed using the χ2 test for categorical variables and the independent t test or Mann-Whitney U test for continuous variables, where appropriate. Baseline clinical, angiographic and procedural characteristics were stratified according to FKBI versus no FKBI.
Cumulative event rates were estimated using the Kaplan-Meier method, stratified by FKBI status. Follow-up was censored at the last known date of follow-up or at 1 year, whichever came first. Comparisons in outcomes between FKBI and no FKBI were assessed using the log rank test. Subsequently, clinical outcomes between the FKBI group and the no-FKBI group were again compared, after excluding patients presenting with ST segment elevation MI (STEMI), since it was expected that patients with STEMI as initial diagnosis would have a higher mortality rate not necessarily being related to the PCI procedure and FKBI.
Univariable logistic regression analyses were performed to identify variables to be associated with FKBI, using all available clinical, angiographic and procedural variables. Subsequently, variables significantly associated with FKBI in these univariate analyses (p<0.1) were all entered in a multivariable logistic regression model. If a variable had more than 5% cases with missing values, an indicator of missingness was created and included in the multivariable model. Variables were considered independently associated with FKBI if the p value was below 0.05 in the multivariable model. Resultant propensity scores derived from this model were used to propensity-adjust for FKBI status on 1-year cardiac death.
All statistical analyses were performed using the SPSS software package (V.19.0, IBM, Chicago, Illinois, USA).
A total of 745 patients with information on FKBI were included in the current analyses. FKBI inflation was successfully performed in 624 patients. Patient baseline and angiographic characteristics according to FKBI status are outlined in table 1. There were several significant differences in baseline clinical characteristics between patients with and without FKBI performed. In the no-FKBI group, more patients had diabetes mellitus, renal dysfunction, previous MI and STEMI as indication for PCI, while less patients had hypercholesterolaemia. There were also differences observed in baseline angiographic characteristics: in the FKBI group, there were less bifurcations with a narrow (<30°) angle, larger reference vessel diameter of the MB and the SB, and a longer MB lesion length.
Procedural characteristics stratified by FKBI are outlined in table 2. MB stent diameter was larger in the FKBI group compared with the no-FKBI group. There were no differences in MB stent types (DES vs BMS vs endothelial progenitor cell capturing stents) between the FKBI and no-FKBI groups, however there were differences regarding platform design.
One-year clinical outcomes are summarised in table 3. Follow-up data was available in 717 (96%) patients. Median follow-up was 190 days (175–364 days). Cardiac death occurred more often in the no-FKBI group (4.6% vs 1.7%, respectively, p=0.017). No statistically significant differences were observed concerning other clinical outcomes. One-year TVF rates was 10.1% in the no-FKBI group and 9.2% in the FKBI group (p=0.257). After excluding patients presenting with STEMI, the difference in cardiac death rate was no longer observed (3.3% in the no-FKBI group vs 1.6% in the FKBI group, p=0.133). Furthermore, after adjusting for potential confounders to perform FKBI by propensity adjustment, the HR of FKBI for cardiac death was closer to equivalence and also no longer statistically significant (unadjusted HR 0.28, 95% CI 0.09 to 0.86, p=0.026; adjusted HR 0.44, 95% CI 0.11 to 1.79, p=0.25).
Variables associated with FKBI
Univariable logistic regression analyses identified diabetes mellitus, hypercholesterolaemia, current smoking, previous MI, renal dysfunction, STEMI as indication for PCI, narrow bifurcation angle, a small reference vessel diameter of MB and SB, long MB lesions and MB stent platform as being associated with FKBI use. Multivariable logistic regression analysis (see online supplementary table A) identified renal dysfunction (OR 0.39, 95% CI 0.18 to 0.86, p=0.020), STEMI as PCI indication (OR 0.22, 95% CI 0.09 to 0.53, p=0.001), narrow (<30°) bifurcation angle (OR 0.43, 95% CI 0.24 to 0.77, p=0.004), Endeavor/Sprint MB stent platform (0.44, 95% CI 0.20 to 0.96, p=0.038) and Promus Element MB stent platform (0.32, 95% CI 0.10 to 0.94, p=0.039) as being independently associated with unsuccessful FKBI.
This study provides information on clinical outcomes after PCI of coronary bifurcation lesions using the Tryton stent if successful FKBI could not be achieved. Cardiac death occurred more often in the no-FKBI group. The difference in cardiac death rate might be explained by an unbalance in the risk profile of the patients at baseline. Indeed, a statistically significant difference in cardiac death rate was no longer observed after excluding patients presenting with STEMI, although a causal relation between no FKBI and cardiac death cannot be excluded based on the current data alone. There were no statistically significant differences observed between both groups regarding 1-year MI, TVR, ST and TVF rates. Furthermore, we identified renal dysfunction, STEMI as PCI indication, narrow (<30°) bifurcation angle and certain stent platforms to be independently associated with unsuccessful FKBI.
Variables associated with successful FKBI performance
The specific reason why FKBI was not successfully performed in a fifth of the patients was not captured in the datasets of the original registry studies. Therefore we performed an exploratory analysis to reveal which clinical, angiographic or procedural characteristics were associated with unsuccessful FKBI. We identified renal dysfunction, STEMI as PCI indication, narrow (<30°) bifurcation angle and certain stent platforms to be associated with unsuccessful FKBI. We hypothesised that a known history of renal dysfunction was associated with less successful FKBI because the operator might be reluctant to finalise with FKBI after initial failed attempts of SB rewiring or SB balloon passage in order to avoid excessive contrast use. STEMI could be related with unsuccessful FKBI performance since these patients might represent a more haemodynamic unstable subgroup of patients, including patients in cardiogenic shock, in whom the operator decided not to prolong the procedure unnecessarily after restoration of epicardial blood flow. The association between narrow bifurcation angle and FKBI failure is probably due to difficulties of fenestration of the wire through the MB stent into the SB and subsequent passage of a balloon into the SB. Previous studies on the (mini-) crush two-stent bifurcation technique showed that a high angle between the proximal and distal MB,21 rather than a narrow distal bifurcation angle,15 was associated with FKBI failure. The mechanism behind this is that a sharp proximal to distal MB angle will bend the stent resulting in opening of stent cells in the outer bend towards the SB, facilitating SB access. More studies are needed to investigate whether this mechanism does also apply on the Tryton technique, because in the current study information on proximal to distal MB angle was not available. Lastly, we found an association with certain stent designs and FKBI performance. This might be explained by differences in stent designs resulting in difficulties in wire and balloon passage through stent cells of certain stents. Although there are bench test studies evaluating which stent platforms should be used as MB stent in bifurcation stenting with regard to maximal achievable cell sizes,22 ,23 no studies are performed, to our knowledge, which evaluated differences in stent designs regarding wire and balloon passage.
At 1 year follow-up we observed more cardiac deaths in the no-FKBI group, while no statistical differences in other clinical outcomes were observed between patients with and without FKBI. Most cardiac deaths in the no-FKBI group occurred early after index PCI as shown in figure 3 with an early divergence of the cardiac death event curves. This early cardiac mortality difference might be explained by a selection bias. In the no-FKBI group there were more patients presenting with STEMI which could have resulted in more early cardiac deaths as a result of mechanical complications or lethal arrhythmias after STEMI presentation. Indeed, if patients with STEMI were excluded from the analysis, the difference in cardiac death was no longer observed. Importantly, there were no differences between the two groups concerning ST or MI. More studies, including randomised trials, are needed to evaluate whether the differences in cardiac death rates could be related to FKBI or whether these differences are due to patient selection.
No statistical differences were found between FKBI and no FKBI regarding the efficacy endpoints TVR and TLR. This is somewhat surprising, because in most studies on two-stent bifurcation PCI, FKBI consistently reduced TVR, TLR and binary stenosis rates.13–16 Due to its design, the Tryton stent has some advantages over the classic culotte and crush two-stent techniques which could potentially explain this observation. The large-sized cells of the proximal zone of the Tryton stent allow easy delivery of the MB stent and provide the possibility to maximally expand the MB stent, while in the classic culotte technique, the expansion of the stents is limited by the sizes of the stent cells through which the stents are advanced. Furthermore, its specific design with three longitudinal fronds in the proximal zone minimises the amount of metal in the MB, whereas with the crush technique there is an excessive amount of metal at the SB ostium opposite to the carina due to three layers of stent struts.24 It could be hypothesised that these specific features of the Tryton stent overcome the disadvantages of other classic two-stent techniques. As a consequence, the influence of FKBI on clinical outcomes in Tryton procedures might resemble those found in single stenting in which no clinical benefit of FKBI was shown.19 However, it has to be borne in mind that no FKBI does result in non-apposed SB (NASB) struts, jailing the SB. An optical coherence tomography study showed delayed coverage of these NASB struts,25 potentially resulting in higher ST rates. Furthermore, a case report with three-dimensional optical coherence tomography reconstruction26 showed redundant tissue growth on those NASB struts causing focal ostial SB restenosis.
Randomised studies, comparing FKBI with no FKBI in bifurcation procedures using Tryton, are needed to evaluate whether FKBI is really necessary and beneficial with respect to clinical outcomes.
The most important limitation of our study was that the explicit reason why FKBI was not performed was not captured in the dataset. To reveal the potential factors to be responsible for FKBI failure a multivariable analysis was performed. However, such analysis should be interpreted with caution and appreciated as hypothesis-generating, since variables not included in the dataset and considerations of the operator during the procedure are not taken into account. Another limitation was obviously the selection bias for FKBI use. The true effect of FKBI in bifurcation stenting using Tryton should be assessed with a randomised clinical trial, which is planned to be performed by the Nordic-Baltic bifurcation study group. Besides selection bias, another limitation is the relative small sample size of the no-FKBI group. Small differences in clinical outcomes between groups could therefore not be detected due to a lack of power. Furthermore, all angiographic characteristics were visual estimates, which could have resulted in inconsistencies of the angiographic data. No follow-up angiography with intravascular imaging was systematically performed which could have resulted in underdetection of ISR and which could have given more insights in the mechanisms of ISR in patients without FKBI. None of the included registry studies used a clinical endpoint committee to adjudicate the clinical end points, which could have introduced inaccuracies regarding clinical endpoint adjudication.
A lower cardiac death rate was observed in patients in whom FKBI was performed compared with a selection of patients in whom FKBI could not be performed, which might be explained by an unbalance in the risk profile of the patients at baseline. No statistically significant differences were observed regarding ST, re-MI, TLR and TVR rates between both groups. In order to evaluate potential factors to be associated with unsuccessful FKBI, we performed an exploratory analysis revealing renal dysfunction, STEMI as PCI indication, narrow (<30°) bifurcation angle and certain stent platforms independently associated with unsuccessful FKBI. A randomised trial will be needed to investigate the true effect of FKBI on outcomes after coronary bifurcation stenting using Tryton. Until such trial is performed, we recommend to attempt to perform FKBI in every procedure with Tryton.
What is already known on this subject?
Being a two-stent technique, it is recommended by the instructions for use to end a Tryton procedure with final kissing balloon inflation (FKBI), based on previous studies on two-stent techniques using conventional, tubular stents for the treatment of bifurcation lesions. However, FKBI can be technically challenging and time consuming and is therefore not performed in all Tryton cases in daily clinical practice.
What does this study add?
Until to date, data on Tryton procedures without FKBI are lacking and it is unclear whether patients in whom FKBI cannot be performed are at higher risk for the occurrence of clinical adverse events than patients in whom FKBI is successfully performed.
How might this impact on clinical practice?
The current study results are suggesting that if FKBI cannot be performed it does not impact on clinical results during follow-up, although randomised trials are needed to confirm this. Until such trials are performed, we would still recommend attempting to perform a FKBI in every patient treated with the Tryton stent.
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Files in this Data Supplement:
- Data supplement 1 - Online table
Contributors MJG: Collection and analysis of data (Amsterdam registry), Conception and design of study, Analysis and interpretation of data (pooled dataset), Writing the manuscript. SA: Collection and analysis of data (Dublin registry), Critically commenting and amending the manuscript. PD: Conception and design of study, Analysis and interpretation of data (pooled dataset), Writing the manuscript. ML: Collection and analysis of data (Poznan registry), Critically commenting and amending the manuscript. MSN: Collection and analysis of data (Wolverhamtpon registry), Critically commenting and amending the manuscript. EG: Data acquisition (eTryton Spain), Critically commenting and amending the manuscript. AB: Collection and analysis of data (eTryton Spain), Critically commenting and amending the manuscript. PW: Collection of data (Amsterdam registry), Critically commenting and amending the manuscript. KTK: Collection of data (Amsterdam registry), Critically commenting and amending the manuscript. MMV: Collection of data (Amsterdam registry), Critically commenting and amending the manuscript. JPH: Collection of data (Amsterdam registry), Critically commenting and amending the manuscript. YO: Collection and analysis of data (First-in-Man), Critically commenting and amending the manuscript. DPF: Collection and analysis of data (eTryton Benelux/150), Critically commenting and amending the manuscript. ALB: Collection and analysis of data (IUVANT), Writing the manuscript. PRS: Collection and analysis of data (eTryton Benelux/150), Critically commenting and amending the manuscript, JGT: Conception and design of study, Critically commenting and amending the manuscript. RJdW: Collection of data (Amsterdam registry), Conception and design of study, Critically commenting and amending the manuscript. JJW: Collection and analysis of data (Amsterdam registry), Conception and design of study, Writing the manuscript.
Competing interests MJG, ML, MSN, and JJW receive consultancy fees from Tryton Medical. PRS and ALB are members of the Tryton IDE trial steering committee.
Ethics approval Patients signed written informed consent, except if ethics approval was waived by local institutional review boards (IRBs) when Tryton was implanted as part of the daily clinical routine (after the device received CE mark), and the study data could be retrieved from existing clinical patient data.
Provenance and peer review Not commissioned; externally peer reviewed.
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