A coronary CTO is defined as a total occlusion in a coronary artery with noncollateral thrombolysis in myocardial infarction (TIMI) flow grade 0 for at least 3 months.9 Patients were considered to have undergone retrograde CTO PCI if a guidewire was introduced into a collateral channel supplying the target vessel. A procedure was defined as an antegrade wire escalation if no guidewire was introduced into a collateral channel, as previously defined. A procedure was defined as antegrade dissection re-entry (ADR) if wire or device-based vessel dissection was adopted as part of the CTO recanalization strategy, either primarily or as bailout.

A bifurcation lesion is defined as a coronary artery narrowing occurring adjacent to, and/or involving, the origin of a significant SB.10 Provisional stenting refers to the reconstruction of bifurcation anatomy with a single stent, implanted from the proximal to the distal segment of the main vessel (MV) across the ostium of the SB and followed by the systematic proximal optimization technique.10,11 Two-stent techniques use a second stent implantation in the SB, either upfront or as bailout.10 Specific techniques have been extensively studied in the literature and described in detail by dedicated groups of experts.10,11 Anatomical criteria and the risk of SB occlusion/reaccess are key determinants of the treatment strategy, which is based either on MV stenting first (T/TAP-T/T and Protrusion-technique, culotte stenting) or SB stenting first (mini crush, inverted T/TAP, inverted culotte, DK-crush).10,11

The baseline bifurcation anatomy was assessed using the Medina classification.12 The pattern of bifurcation disease was further classified into ‘true’ bifurcation lesions, in which the stenosis diameters in both the main branch and the SB were>50% and ‘false’ bifurcation lesions, in which only the MV or the SB showed significant narrowing. Bifurcation lesions were divided into 3 types according to the SB take-off from the MV; bifurcation lesions within the occluded segment and those located within 5mm of the proximal or distal CTO cap (figure 1). Lesions were further classified into 5 types to agree with relevant published literature.13 The strategy for CTO revascularization and bifurcation treatment was left to the operator's discretion.

Figure 1.

CTO bifurcation lesions divided according to side branch (SB) take-off from the main vessel. A: bifurcation lesion located within 5mm proximal to CTO cap. B: bifurcation lesion arising within the CTO body. C: bifurcation lesion located within 5mm distal to CTO cap. The final post-PCI angiographic result can be seen at the inserts. CTO, chronic total occlusion; PCI, percutaneous coronary intervention; SB, side branch.

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Technical success was defined as angiographic success (final residual stenosis<30% on visual estimation and TIMI flow grade 3 after CTO recanalization). Technical success was defined as residual stenosis of<30% in the MV and a final TIMI flow grade 3 in both branches. Procedural success was defined as angiographic success without the occurrence of in-hospital major adverse cardiac events (MACE).

In-hospital MACE were defined as a composite of non-Q wave and Q wave myocardial infarction (MI), recurrent angina requiring urgent repeat revascularization with PCI or CABG, stroke, death, pericardiocentecis, or surgical drainage of pericardial hematoma. Periprocedural MI definition was derived from the recent Academic Research Consortium-2 consensus document.14

Continuous variables are expressed as the mean±standard deviation and were compared with 1-way analysis of variance. Categorical variables are expressed as percentages and were compared with the chi-square test. IBM SPSS Statistics version 22 software package (IBM Corporation, United States) and R language were used for all analyses. Two-sided P values<.05 were considered as indicative of statistical significance.

Previous series on bifurcation-CTO lesions reported an incidence ranging from 26.5% to 67%.13,15–18 In line with our study (40.4% incidence), Ojeda et al.17 (30.3%), Galassi et al.16 (26.5%) and Baystrukov et al.13 (54.3%) reported single-center experiences and used the same definitions (proximal, within the CTO body, distal bifurcation). Chen et al.18 reported proximal and distal SB arising from the CTO segment (47% incidence), whereas Nikolakopoulos et al.15 reported only bifurcation-CTOs with SB arising within 5mm of the proximal or distal cap (67% incidence).

Procedural success in our study was high, averaging 78.9%. Dedicated groups of experts worldwide have consistently reported success rates in the range of 90% in the last few years.5,19–23 In our study, the procedural complexity of the treated patients was relatively high (J-CTO score 2.30±1.16) compared with that reported in studies based on large scale European24 and Japanese registries.25 Of note, in 2018 the EuroCTO Club reported a mean J-CTO score of 2.37±1.14 in failed cases vs 2.08±1.15 in successful cases (P<.001; 17 626 procedures cohort).24

As per European practice,24 the predominant revascularization strategy was the antegrade approach (71.9%), followed by retrograde (19.9%) and ADR (8.2%). CTO crossing was successful with soft and moderate stiffness wires in most cases, reflecting contemporary technique and wire technology development.24

The overall J-CTO score and PROGRESS-CTO score in our study were 2.30±1.16 and 1.37±0.94, respectively. Procedural complexity was higher in CTOs involving a bifurcation lesion than in non–BIF-CTO, as assessed by both J-CTO score (2.42±1.01 vs 2.21±1.23; P=.025) and PROGRESS-CTO score (1.60±0.95 vs 1.22±0.90; P<.001) (figure 2). Similar to our study, Nikolakopoulos et al.15 reported a higher J-CTO score in BIF-CTO patients. All the other relevant studies reported data from relatively small cohorts and identified no differences in procedural complexity.13,16–18 The PROGRESS-CTO complication score was 2.66±1.85 overall and was similar in both arms (P=.147).

Procedural success was similar in the 2 treatment cohorts (80.4% for BIF-CTO patients, 77.8% for non–BIF-CTO patients; P=.447), even though procedural complexity was higher in patients with BIF-CTO, as assessed by J-CTO and PROGRESS-CTO scores (figure 2). All other relevant studies reported lower procedural success rates in CTO involving bifurcation lesions, with Galassi et al.16 reporting a single operator experience and Nikolakopoulos et al.15 reporting data from a global US registry. Compared with the above studies, in our cohort the provisional stenting strategy for bifurcation treatment was predominant (93.4%) and ADR techniques were infrequently adopted (8.2%).

Bifurcation treatment has greatly evolved over the years and has reached a period of standardization in terminology and practice.10 Provisional stenting has been established as the preferred treatment modality, since complex coronary interventions with 2 stents have been associated with greater periprocedural MI, target lesion revascularization, and mortality.26–28 In our study, the provisional strategy was the predominant approach and was applied in 93.46% of bifurcations, matching the results of other contemporary European cohorts.17 The ADR approach, by definition responsible for controlled vessel dissection in contemporary CTO PCI, had low adoption in our center (8.2% in BIF-CTO patients), accounting, to a certain extent, for the low use of techniques requiring 2-stent implantation (6.5%).

In the context of CTO PCI, the presence of dissection affecting the SB origin has been identified as a predictor for the adoption of the 2-stent strategy,17 leading to a 46% adoption of 2-stent techniques in a single operator cohort.16 Larger studies reported the use of the 2-stent technique in the range of 8% to 8.9%.17,29 Adachi et al.29 reported that 2-stent techniques were more efficient in preserving SB patency for bifurcations located within the CTO body. Ojeda et al.30 reported no differences in procedural and mid-term clinical outcomes between 1-stent and 2-stent techniques for the treatment of CTO bifurcation lesions. Interestingly, a single center randomized study comparing the mini crush technique and the provisional approach in CTOs involving bifurcation lesions revealed no differences in angiographic or clinical success but did reveal improved 1-year outcomes with the mini crush technique.13

SB patency with TIMI III flow was achieved in 92.2% of the bifurcations treated. Baseline SB wiring, a well identified predictor of procedural success in non-CTO bifurcation PCI, 31 was achieved in all SBs located proximal to the CTO, but in only 51.8% of the SBs located within or distal to the CTO. A previous study reported unsuccessful baseline SB wiring in 25% of nonproximal BIF-CTO,17 which can be largely attributed to dissections involving the carina during CTO crossing. A dual lumen microcatheter was used for SB wiring in 10.6% of the patients.

SB compromise is a well identified cause of periprocedural myocardial injury in coronary interventions.32 In the context of CTO PCI, Adachi et al.29 identified the presence of stenosis in the SB, bifurcations located within the occluded segment and subintimal tracking at the SB ostium as independent predictors of a suboptimal result in SB. In that study, a suboptimal SB result itself, had an impact on target lesion revascularization of the main branch for lesions located in the right coronary artery.29 Another single-center CTO PCI study identified SB occlusion as the only parameter associated with troponin elevation during the procedure.33 Elevation of cardiac biomarkers reflects myocardial necrosis and has been linked to an increased risk of future cardiac events.33–35

In this study, the presence of a bifurcation had no impact on the in-hospital complication rate following CTO revascularization. In our cohort, the key determinants for this result were operator expertise, a predominantly provisional stenting strategy for bifurcation treatment (93.4%), and low adoption of dissection re-entry techniques for CTO crossing (8.2%). Prior studies identified higher periprocedural MI17 and more frequent coronary perforation and cardiac tamponade in CTOs with bifurcation lesions.16 In the first study, ADR was applied in up to 31% of the cases and in the second study, 1-stent techniques for bifurcation treatment were applied in only 54% of the patients. In our cohort, periprocedural MI was documented in 2.4% of the patients overall. Of note, periprocedural MI in CTOs involving bifurcations seems to affect MACE-free survival and mortality at 12 months.17,36

Our study has a number of limitations. First, all patients in our registry were treated by experienced operators, with varied experience in CTO treatment and extensive experience in the treatment of bifurcation lesions. The data presented in this study reflect their practice and might not be generalizable to centers with limited complex PCI experience. Second, this is an observational retrospective single center study, with all the inherent bias of this kind of design. Yet, no randomized data are available on this topic. Third, the angiographic data were estimated by visual assessment only; no quantitative coronary angiographic analysis or core laboratory adjudication was performed. Fourth, no follow-up was available in our study.