Abstract
Background
Intracoronary imaging improves clinical outcomes after stenting of complex coronary bifurcation lesions (CBLs), but the impact of Medina classification-based CBL distribution on outcomes of imaging-guided bifurcation stenting is unclear.
Methods
In this integrated analysis of four previous studies, in which all CBLs were treated with drug-eluting stents under intravascular ultrasound or optical coherence tomography guidance, the distribution of 763 CBLs was assessed using angiographic Medina classification. Major adverse cardiac events (MACE), including target lesion revascularization (TLR), myocardial infarction, stent thrombosis, and cardiac death, were investigated at 1-year follow-up.
Results
The most and least prevalent Medina subtypes were 0-1-0 (27.9 %) and 0-0-1 lesions (2.8 %). The most and least frequent MACE/TLR rates were 18.2 %/18.2 % for 0-0-1 lesions and 4.1 %/2.8 % for 0-1-0 lesions. Risks were higher for 0-0-1 lesions than for 0-1-0 lesions for both MACE (hazard ratio [HR]: 4.04, 95 % confidence interval [CI]: 1.21–13.45, p = 0.02) and TLR (HR: 6.19, 95 % CI: 1.69–22.74, p = 0.006). MACE rates were similar for true and non-true CBLs excluding 0-0-1 lesions (8.2 % and 5.9 %, HR 1.54, 95 % CI: 0.86–2.77, p = 0.15), while MACE (HR: 3.25, 95 % CI: 1.10–9.63, p = 0.03) and TLR (HR: 4.24, 95 % CI: 1.38–12.96, p = 0.01) risks were higher for 0-0-1 lesions.
Conclusions
This integrated analysis of imaging-guided bifurcation stenting demonstrated similar clinical outcomes in true and non-true CBLs, except for 0-0-1 lesions, which had a significantly higher risk of MACE/TLR.
Keywords: Coronary bifurcation, Drug-eluting stent, Intracoronary imaging, Medina classification
1. Introduction
The Medina classification is widely used to characterise coronary bifurcation lesions (CBLs) by indicating the presence or absence of significant stenosis in the proximal main vessel (MV), distal MV, and side branches (SB) during coronary angiography [1], [2]. This classification helps understand lesion distribution, stratify percutaneous coronary intervention (PCI), and predict prognosis. True CBLs (those with significant stenosis in both the MV and SB) require more SB treatment and complex procedures, such as kissing balloon inflation (KBI) and two-stent deployment, and are associated with an increased risk of target lesion failure compared with non-true CBLs [3], [4]. However, in complex true CBLs, which have more diffuse or tighter SB stenosis and calcified lesions, elective two-stenting had superior clinical outcomes compared with provisional stenting [5], [6]. Although the impact of lesion subgroups in the Medina classification has not been systematically investigated, a recent analysis revealed that Medina 0-0-1 lesions (SB lesions only) and Medina 1-1-1 lesions (the most complex) had a higher risk of target lesion failure than Medina 1-0-0 lesions (hazard ratios [HRs] 4.0 and 2.6, respectively). The paradoxical finding of a higher risk associated with both the simplest and most complex lesions is striking, but might be influenced by the limited use of imaging guidance (12 %) [7]. Imaging guidance enhances accurate lesion assessment, and PCI optimisation and reduces unnecessary SB stenting [8], [9]. However, the impact of imaging guidance on CBL intervention by CBL distribution has not yet been studied on a large scale. This study explored the influence of the CBL distribution according to the angiographic Medina classification on the clinical outcomes of CBL interventions using comprehensive imaging guidance.
2. Methods
2.1. Study population
The study included 778 CBLs from 769 patients treated with drug-eluting stent (DES) implantation under the guidance of intravascular ultrasound (IVUS) or optical coherence tomography (OCT)/optical frequency domain imaging (OFDI) in four previous studies (Fig. 1). The studies included two multicentre prospective registry studies (J-REVERSE; 300 CBLs with IVUS guidance [10]; and 3D OCT Bifurcation Registry; 168 CBLs with OCT guidance [11]), one multicentre randomised study (PROPOT; 119 CBLs with OCT/OFDI guidance) [12], and one single-centre prospective registry study (Glider Balloon Registry; 201 CBLs with IVUS or OCT/OFDI guidance) [13]. Common inclusion criteria were: ≥ 75 % stenosis in the MV, with or without ≥ 75 % stenosis in the SB; MV reference diameter ≥ 2.5 mm; and SB reference diameter ≥ 2.0 mm. Mandatory imaging was performed during and after the procedures. The exclusion criteria included contraindications to antiplatelet or anticoagulant therapy, allergies to contrast agents, in-stent restenosis, cardiogenic shock, chronic total occlusion, and bypass graft lesions. Medina classifications were determined by on-site visual assessment of baseline coronary angiography, and were expressed as the presence (“1″) or absence (”0″) of significant stenosis in the proximal MV, distal MV, and SB. Significant stenosis was regarded as ≥ 75 % stenosis, or ≥ 50 % stenosis in the left main coronary artery. True CBL (both MV and SB stenosis) was defined as Medina 1-1-1, 1-0-1, or 0-1-1 lesions. After excluding 15 cases without a reported classification, 763 CBL cases were analysed; 390 (51 %) using IVUS guidance and 373 (49 %) using OCT/OFDI guidance. Clinical events, including target lesion revascularisation (TLR), cardiac death, myocardial infarction, and definite stent thrombosis, were recorded 9–12 months after CBL intervention. Ethical approval was obtained for each study and the patients provided written informed consent in accordance with the Declaration of Helsinki.
Fig. 1.
Study flow and integrated analysis. The endpoint of the study is listed at the bottom right. IVUS: intravascular ultrasound; OCT: optical coherence tomography; CBL: coronary bifurcation lesion.
2.2. PCI
After the administration of an appropriate dose of a combination of dual antiplatelet agents, provisional CBL stenting using a DES is recommended. In cases of occlusion, serious dissection, or diffuse lesions in the non-stenting branch, two-stenting was performed [10], [11], [12], [13].
2.3. Outcome
The primary outcomes were major adverse cardiac events (MACE), a composite of TLR due to PCI or surgery, cardiac death, myocardial infarction, and definite stent thrombosis.
2.4. Statistical analysis
The data were expressed as mean ± standard deviation, or number and percentage. Between-group comparisons of continuous variables were performed using a one-way analysis of variance. Between-group differences in counts and percentages were examined using chi-squared tests and corrected using Fisher’s exact test when appropriate. A Cox proportional hazards regression analysis was performed using Medina 0-1-0 as a reference, with adjustments for the following factors: acute coronary syndrome, lesion location, age, sex, hypertension, diabetes mellitus, dyslipidaemia, and current smoking. All p-values were two-sided and considered statistically significant at p < 0.05. All analyses were performed using R (version 3.6.1; R Foundation for Statistical Computing, Vienna, Austria).
3. Results
3.1. Lesion distribution according to the Medina classification
As shown in Fig. 2, the CBL subsets 1-1-1, 1-0-1, 0-1-1, 1-1-0, 1-0-0, 0-1-0, and 0-0-1 accounted for 17.4, 6.3, 12.6, 18.3, 12.9, 27.9, and 2.8 % of all CBLs, respectively. The most prevalent were 0-1-0 lesions; the least prevalent were 0-0-1 lesions.
Fig. 2.
Distribution of Medina classification in coronary bifurcation lesions (CBLs).
3.2. Baseline patient characteristics
Patients’ baseline characteristics are summarised in Table 1. Mean ages ranged from 66 to 71 years and males accounted for 69–89 %. Hypertension was present in 73–82 %, diabetes mellitus in 33–43 %, dyslipidaemia in 61–82 %, and current smokers accounted for 16–28 %. No significant difference was observed in baseline characteristics among the Medina classification groups. Acute coronary syndrome was frequently observed in 1-1-1, 1-1-0, and 0-0-1 lesions (18–20 %) and less frequently in 1-0-1, 1-0-0, and 0-1-0 lesions (6–9 %; p = 0.02).
Table 1.
Patient background in coronary bifurcation lesion subsets of Medina classification.
| Medina classification | number | Age (year old) |
Male | Hypertension | Diabetes mellitus | Dyslipidemia | Current smoking | Acute coronary syndrome |
|---|---|---|---|---|---|---|---|---|
| 1-1-1 | 135 | 69.1 ± 11.0 | 72 % | 79 % | 37 % | 74 % | 27 % | 20 % |
| 1-0-1 | 49 | 70.1 ± 9.9 | 69 % | 73 % | 33 % | 61 % | 16 % | 6 % |
| 0-1-1 | 98 | 68.7 ± 10.1 | 76 % | 82 % | 50 % | 71 % | 28 % | 10 % |
| 1-1-0 | 142 | 69.7 ± 9.7 | 82 % | 82 % | 40 % | 79 % | 22 % | 18 % |
| 1-0-0 | 100 | 66.4 ± 10.1 | 89 % | 80 % | 38 % | 79 % | 19 % | 8 % |
| 0-1-0 | 217 | 68.8 ± 9.6 | 77 % | 75 % | 43 % | 71 % | 24 % | 9 % |
| 0-0-1 | 22 | 70.8 ± 8.9 | 77 % | 77 % | 41 % | 82 % | 27 % | 18 % |
| P-value | 0.10 | 0.81 | 0.99 | 0.71 | 0.89 | 0.70 | 0.02 |
3.3. Lesion characteristics
As shown in Table 2, the left anterior descending artery (LAD) was the most frequently treated artery in all Medina classifications (48–68 %). The 0-0-1 lesions in the left circumflex artery (23 %) and the 1-0-0 lesions in the right coronary artery (20 %, p = 0.002) were treated more frequently than the other CBLs. The 0-1-1 lesion was less frequently observed in the left main (LM) coronary artery (7 %, p = 0.03).
Table 2.
Lesion location and procedure of coronary bifurcation intervention in lesion subsets of Medina classification.
| Medina classification | Lesion location |
Main vessel stent |
Side branch stent |
2-stent | POT | KBI | SB dilation alone | Any SB dilation | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| LAD | LCX | RCA | LM | Incidence | Size (mm) | Length (mm) | Incidence | Size (mm) | Length (mm) | ||||||
| 1-1-1 | 67 % | 10 % | 4 % | 19 % | 100 % | 3.0 ± 0.4 | 22.6 ± 6.8 | 19 % | 2.6 ± 0.3 | 22.0 ± 8.1 | 19 % | 47 % | 41 % | 50 % | 92 % |
| 1-0-1 | 59 % | 8 % | 8 % | 24 % | 100 % | 3.0 ± 0.4 | 24.1 ± 6.3 | 4 % | 2.5 ± 0.0 | 11.5 ± 3.5 | 4 % | 43 % | 47 % | 31 % | 78 % |
| 0-1-1 | 68 % | 19 % | 5 % | 7 % | 100 % | 3.1 ± 0.4 | 24.5 ± 6.5 | 9 % | 2.6 ± 0.3 | 23.8 ± 8.9 | 10 % | 45 % | 41 % | 41 % | 82 % |
| 1-1-0 | 48 % | 19 % | 8 % | 25 % | 100 % | 3.0 ± 0.4 | 22.3 ± 7.3 | 2 % | 2.4 ± 0.1 | 18.5 ± 5.5 | 2 % | 58 % | 40 % | 44 % | 85 % |
| 1-0-0 | 56 % | 12 % | 20 % | 12 % | 100 % | 2.9 ± 0.5 | 24.2 ± 6.3 | 0 % | – | – | 0 % | 57 % | 39 % | 28 % | 67 % |
| 0-1-0 | 57 % | 17 % | 7 % | 19 % | 100 % | 3.1 ± 0.4 | 21.5 ± 6.2 | 3 % | 2.6 ± 0.2 | 20.5 ± 9.5 | 3 % | 44 % | 54 % | 23 % | 76 % |
| 0-0-1 | 55 % | 23 % | 9 % | 14 % | 91 % | 2.9 ± 0.4 | 22.7 ± 7.0 | 18 % | 2.6 ± 0.1 | 16.5 ± 3.8 | 9 % | 32 % | 59 % | 27 % | 86 % |
| P-value | 0.41 | 0.25 | 0.002 | 0.03 | 1.00 | 0.007 | 0.004 | <0.001 | 0.89 | 0.39 | <0.001 | 0.35 | 0.31 | <0.001 | 0.001 |
LAD: left anterior descending artery, LCX: left circumflex artery, RCA: right coronary artery, LM: left main coronary artery, POT: proximal optimization technique, KBI: kissing balloon inflation, SB: side branch.
3.4. Procedure characteristics
As shown in Table 2, crossover stenting from the proximal to the distal MV was performed in all CBLs except for 0-0-1 lesions (91 %). SB stenting was frequently performed for 1-1-1 (19 %) and 0-0-1 (18 %, P < 0.001) lesions. More two-stent deployment was performed for 0-0-1 lesions (9 %) and true CBL (1-1-1 lesions, 19 %; 0-1-1 lesions, 10 %; p < 0.001). Although the incidence of usage the proximal optimisation technique (POT) was not significantly different among between lesions, fewer POT procedures were performed for 0-0-1 lesions (32 %). SB dilation (KBI or SB dilation alone) was performed most frequently in 1-1-1 and 0-0-1 lesions (92 % and 86 %, respectively) and least frequently in 1-0-0 and 0-1-0 lesions (67 % and 76 %, respectively; p = 0.001).
3.5. Clinical events
As shown in Fig. 3, MACE rates were highest for 0-0-1 lesions (18.2 %) and lowest for 0-1-0 lesions (4.1 %). The HR after adjusting for confounding factors using 0-1-0 lesions (lowest MACE rate) as a reference was significantly increased only in 0-0-1 lesions (HR 4.04, 95 % confidence interval [CI]:1.31–13.45, p = 0.02), not in any other lesion subset, even 1-1-1 lesions. The survival rate up to 1 year was also significantly decreased only for 0-0-1 lesions (0.758, 95 % CI: 0.378–0.924, p = 0.02), as shown in the Supplementary Figure. The TLR rates are indicated in Fig. 4, and the highest and lowest prevalence rates of TLR were similar in 0-0-1 and 0-1-0 lesions (18.2 % and 2.8 %, respectively). The adjusted HR was significantly elevated only for 0-0-1 lesions (HR 6.19, 95 % CI: 1.69–22.74, p = 0.006).
Fig. 3.
Major adverse cardiac events at 1-year follow-up for each lesion subset of the Medina classification. Lower table shows hazard analysis using the value in the 0-1-0 lesion as a reference. CBL: coronary bifurcation lesion.
Fig. 4.
Target lesion revascularization at the 1-year follow-up for each lesion subset of the Medina classification. Lower table shows hazard analysis using the value in the 0-1-0 lesion as a reference. CBL: coronary bifurcation lesion.
In the hazard regression analysis using non-true CBLs other than 0-0-1 lesions as a reference, true CBLs did not present significantly higher adjusted HRs for 1-year MACE (HR: 1.54, 95 % CI: 0.86–2.77, p = 0.15), whereas 0-0-1 lesions presented an elevated risk (HR: 3.25, 95 % CI: 1.10–9.63, p = 0.03). Similarly, for 1-year TLR, true CBLs did not present a significant risk elevation (HR: 1.06, 95 % CI: 0.51–2.22, p = 0.87), whereas the TLR risk was higher for the 0-0-1 lesion (HR: 4.24, 95 % CI: 1.39–12.96, p = 0.01).
4. Discussion
4.1. Medina classification lesion distribution
The present study with complete imaging guidance demonstrated fewer true CBLs (36.3 % vs. 47–52 %) [4], [7], [14], [15] and LM bifurcations (18 % vs. 23–30 %) [4], [14], [15] than those identified in previous studies with less imaging guidance (14–39 %) (Table 3). Overestimation of Medina classification based on angiography was reported in comparison with the classification based on coronary computed tomography angiography (CCTA), with a discordance in 63 % and decrease in the incidence of true CBL from 61.3 % to 44.8 % [16]. Considering the tendency to overestimate lumen narrowing in CCTA compared to that revealed by intracoronary imaging due to the blooming of calcification, some of the true CBLs may have been overestimated. The on-site imaging observations used in the present study might have affected the assessment of the angiography-based Medina classification, corrected the actual plaque distribution, and recruited more angiographically nonsignificant lesions with concrete atheromatous plaques. Considering these overestimations of angiography-based assessments, the lesion distribution in the present study was appropriate and unlikely to have been influenced by a selection bias toward lower lesion complexity or underestimation.
Table 3.
Coronary bifurcation lesion distribution according to Medina classification in previous and present studies.
| COBIS II4 | Vergara et al.14 | BIFURCAT15 | e-Ultimaster7 | CT-PRECISION16 | Present study | |
|---|---|---|---|---|---|---|
| Case number | 2897 | 1368 | 5537 | 4003 | 400 | 763 |
| Imaging-guide PCI | 39 % | 39 % | ND | 14 % | CCTA 100 % | 100 % |
| LM bifurcation | 29 % | 23 % | 30 % | 12 % | ND | 18 % |
| Medina classification | ||||||
| 1-1-1 | 32.4 % | 32.6 % | 32.1 % | 35.5 % | 32.8 % | 17.4 % |
| 0-1-1 | 12.2 % | 2.3 % | 7.7 % | 7.2 % | 8.0 % | 12.6 % |
| 1-0-1 | 7.3 % | 1.7 % | 7.9 % | 8.7 % | 4.0 % | 6.3 % |
| 1-1-0 | 14.7 % | 51.6 % | 24.7 % | 26.8 % | 27.2 % | 18.3 % |
| 1-0-0 | 11.9 % | 10.5 % | 9.8 % | 8.3 % | 13.8 % | 12.9 % |
| 0-1-0 | 17.5 % | 0.4 % | 13.6 % | 10.0 % | 14.2 % | 27.9 % |
| 0-0-1 | 3.9 % | 1.0 % | 4.2 % | 3.5 % | 0 % | 2.8 % |
PCI: percutaneous coronary intervention, LM: left main coronary artery, ND: not described, CCTA: coronary computed tomography angiography.
4.2. True CBL vs. Non-true CBLs other than 0-0-1 lesions
Worse MACE was reported in cases with true CBLs compared with non-true CBLs (HR 1.39) in 2,897 patients in the COBIS II study [4], and worse target lesion failure occurred in cases with 1-1-1 lesions (HR 2.6) compared to that observed in cases with 1–0-0 lesions in 4003 patients in the e-Ultimaster registry [7]. This is because more complex anatomy results in myocardial ischaemia or insufficient lumen dilation [3], [4], [7]. Pre-PCI intracoronary imaging facilitates the development of an effective PCI strategy and the selection of optimal device size and length by referring to lesion severity, distribution, plaque morphology, and reference diameter [8], [9]. Post-PCI intracoronary imaging contributes to the reduction of procedural failures, such as stent under-expansion, mal-apposition, deformation, intra-stent protrusion, and edge dissection [8], [9]. In particular, imaging of the SB is useful for identifying actual lumen dilation, the degree of dissection, and determining the necessity of more aggressive treatment (i.e., additional SB stenting, elective two-stenting, KBI, and more SB ostial dilation). In the present study, two-stenting was less commonly used for true CBLs (total 13 %, minimum 4 % in 1–0-1 lesion, maximum 19 % in 1-1-1 lesion) compared with previous studies (22–47 %) [17], [4], [5], [6], [7]. This was because SB dissection after balloon dilation was assessed accurately in the imaging and was relatively mild due to optimal balloon sizing based on the pre-PCI imaging observation, even when the angiographic image remained indistinct. Angiographic assessment of the residual SB ostial lesion was difficult because of SB foreshortening at a particular angle, overlapping of the branches, uncertain visualisation of the bifurcation site, and ambiguous images reflected by the SB ostial stent struts. An increase in imaging guidance avoided unnecessary two-stent deployment for true CBLs, regardless of the uncertainty of the angiographic findings.
In the present study, with complete imaging guidance, no significant increase in the HR for MACE or TLR was observed in the true CBL group at 1-year follow-up. Although imaging guidance can overcome these events, regardless of the complexity of the procedure, a longer follow-up study is warranted to detect long-progressed in-stent neo-atherosclerosis, asymptomatic organised thrombus accumulation, and myocardial infarction due to late-phase stent thrombosis.
4.3. 0-0-1 lesions
The present study found worse clinical outcomes in 0-0-1 lesions, despite complete imaging guidance. Previous IVUS studies demonstrated that SB ostial lesions alone were rare (1 % of cases), and consecutive atherosclerotic plaques were found in the proximal MV [18]. Although angiography did not reveal significant MV stenosis, imaging revealed mild-to-moderate plaques. The treatment approach for 0-0-1 lesions was similar to that for true CBLs, including higher rates of MV crossover stenting (91 % vs. 100 % true CBLs), SB stenting (18 % vs. 13 %), two-stenting (9 % vs. 13 %), and SB dilation (86 % vs. 86 %). These treatments aim to address the severity of myocardial ischaemia induced by MV lesions and avoid adverse effects (MV compromise and SB stent protrusion into the MV ostium). Compared with other non-true CBLs, 0-0-1 lesions exhibited higher frequencies of SB stenting (18 % vs. 2 %) and two-stenting (9 % vs. 2 %). These are characterised by fibrocalcific plaques and negative remodelling [19], leading to limited lumen gain and an increased risk of recoil after dilation. Rheological turbulence in the SB ostium contributes to low shear stress [20], promoting neointimal hyperplasia and thrombotic events. Hinge motion of the SB ostium further increases the risk of stent fracture and reactive intimal hyperplasia [21].
The e-Ultimaster study showed an elevated risk of cardiac death with 0-0-1 lesions (HR = 4.6) [7], whereas the present study observed no cardiac death. Complete imaging guidance facilitated optimal device and procedure selection and reduced unnecessary treatments such as two-stenting (9 % vs. 27 %) [7]. While elective two-stenting has limited superiority in complex true CBLs [5], [6], [17], [22], it should generally be avoided in 0-0-1 lesions, except when accompanied by diffuse lesions or severe dissection in the MV.
Preventing the overtreatment of 0-0-1 lesions is crucial. In a previous study, computed tomography showed that SB with a perfusion territory > 10 % of the left ventricle, indicating the superiority of PCI over medical therapy, was 21 % for non-LM bifurcations and 96 % for LM bifurcations.[23]. Discordance between angiographically significant stenosis in stent-jailed SBs and physiological assessment is common (27–29 %), highlighting the usefulness of physiological assessment for avoiding unnecessary additional SB treatment [24].
Crossover stenting from the proximal MV to the SB, followed by use of POT and KBI, is a reasonable treatment option [25]. However, there is a higher TLR rate for LM-LCX crossover stenting compared with LM-LAD stenting (18.2 % vs. 3.0 %) [26]. Wide bifurcation angles and dynamic hinge motion in the LM bifurcation may have contributed to this outcome. Another treatment option involves stent deployment by nailing the SB ostium, but this carries the risk of missing an SB ostial lesion or protruding into the MV ostium. Precise identification of the SB ostium during imaging and fluoroscopic recording enhances the accuracy of stent positioning. However, this procedure remains challenging because of cardiac motion, patient breathing, and stent migration caused by the distal balloon contact with the vessel. Stent nailing for LAD ostial lesions has been associated with higher rates of target vessel revascularization than those associated with LM-LAD crossover stenting (21.0 % vs. 5.6 %, respectively) [27].
Although not examined in this study, previous studies have suggested the efficacy of drug-coated balloon (DCB) treatment in SB. The DEBSIDE trial observed a lower late lumen loss in the SB (-0.04 ± 0.34 mm) at 6-month follow-up angiography when 50 patients received DES in the MV and DCB treatment in the SB [28]. In a randomised trial (PEPCAD-BIF) involving 64 patients with branch ostial lesions (0-1-0 or 0-0-1 lesions), DCB treatment demonstrated a significantly lower late lumen loss (0.13 mm vs. 0.51 mm) and restenosis rate (6 % vs. 26 %) compared with plain balloon angioplasty [29]. However, among the 49 patients with 0-0-1 lesions who were treated with DCB after cutting balloon dilation, the target lesion failure rate at 1-year follow-up was 14 %[30], which was relatively higher than that observed in other studies where DCB treatment was used for other CBL subsets. Whether DCB treatment can effectively address the specific characteristics of 0-0-1 lesions remains unclear.
4.4. Medina classification in imaging-guided PCI
Angiography-based Medina classification is invaluable for the swift evaluation of CBL distribution and stratification of PCI procedure. The most complex true CBLs (1-1-1 lesions) more frequently necessitated two-stent deployment and SB dilation. Nonetheless, the precise evaluation of pre-PCI imaging mitigated potential overestimations and subsequent overtreatment resulting from ambiguous angiographic findings in CBLs. Procedural imaging guidance enabled more optimal PCI, which ultimately led to a decreased risk of MACE and TLR in true CBLs, as well as in non-true CBLs other than 0-0-1 lesions. This contrasts with previous studies that used limited imaging. Even with imaging guidance, 0-0-1 lesions continued to exhibit a higher risk of MACE and TLR, warranting further investigation into management and outcomes for these lesions.
4.5. Study limitations
The study included three nonrandomised trials, so the selection of the lesion and interventional treatment included some bias. The SB dilation methods varied among the trials. The identification of the Medina classification on baseline angiography may have been influenced by on-site imaging observations. SB stenosis after MV stenting was assessed only by visual estimation on angiography and not by physiological assessment. Patients undergoing SB or distal MV ostial stenting were excluded from the study. Clinical outcomes at long-term follow-up have not yet been investigated.
5. Conclusions
Imaging-guided bifurcation stenting yields the highest and lowest MACE/TLR rates in 0-0-1 and 0-1-0 lesions, respectively. Imaging guidance improves clinical outcomes for complex CBLs and leads to comparable outcomes for true and non-true CBLs, except for 0-0-1 lesions. Even with the aid of imaging guidance, 0-0-1 lesions have a higher risk of MACE and TLR similarly treated as in true CBLs.
CRediT authorship contribution statement
Yoshinobu Murasato: Conceptualization, Writing – original draft, Formal analysis, Data curation, Funding acquisition. Yoshihisa Kinoshita: Investigation, Funding acquisition, Writing – review & editing. Masahiro Yamawaki: . Takayuki Okamura: Investigation, Formal analysis, Data curation, Writing – review & editing. Ryoji Nagoshi: Investigation, Formal analysis, Data curation, Writing – review & editing. Yusuke Watanabe: Investigation, Formal analysis, Data curation, Writing – review & editing. Nobuaki Suzuki: Investigation, Formal analysis, Data curation, Writing – review & editing. Takahiro Mori: Investigation, Formal analysis, Writing – review & editing. Toshiro Shinke: Investigation, Formal analysis, Writing – review & editing. Junya Shite: Investigation, Formal analysis, Writing – review & editing, Funding acquisition. Ken Kozuma: Investigation, Formal analysis, Writing – review & editing, Funding acquisition.
Declaration of Competing Interest
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Y. Murasato has received speaker fees from Abbott Medical, Medtronic, Terumo, and Kaneka. N. Suzuki has received speaker fees from Abbott Medical, Actelion Pharmaceuticals, Astellas, Astellas-Amgen, Bayer Healthcare Pharmaceuticals, Boston Scientific, Bristol Myers Squibb, Daiichi Sankyo, Nipro, Otsuka, Sanofi and Toa Eiyo. T. Okamura and J. Shite have received honoraria for technical consulting from Abbott Medical. K. Kozuma received lecture fees from Boston Scientific, Abbott Medical, Medtronic, Otsuka, Takeda, Daiichi-Sankyo, Amgen, Novartis, Behringer, Bayer, Life Science Institute, Mochida, and Zeon Medical, and research grants from Boston Scientific and Abbott Medical. The other authors have no conflicts of interest to declare.
Acknowledgments
None.
Funding
J-REVERSE was supported by unrestricted research grants from Abbott Vascular, Cordis Corporation, Orbus Neich, and Kaneka Corporation. 3D-OCT Bifurcation Registry was supported by an unrestricted research grant from Abbott Vascular. PROPOT was funded by Medtronic Japan.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.ijcha.2023.101311.
Appendix A. Supplementary material
The following are the Supplementary data to this article:
Supplementary figure 1.
References
- 1.Medina A., Suarez de Lezo J., Pan M. A new classification of coronary bifurcation lesions. Rev Esp Cardiol. 2006;59:183. [PubMed] [Google Scholar]
- 2.Sawaya F.J., Lefevre T., Chevalier B., Garot P., Hovasse T., Morice M.C., et al. Contemporary Approach to Coronary Bifurcation Lesion Treatment. JACC Cardiovasc Interv. 2016;9:1861–1878. doi: 10.1016/j.jcin.2016.06.056. [DOI] [PubMed] [Google Scholar]
- 3.Tsuchida K., Colombo A., Lefevre T., Oldroyd K.G., Guetta V., Guagliumi G., et al. The clinical outcome of percutaneous treatment of bifurcation lesions in multivessel coronary artery disease with the sirolimus-eluting stent: insights from the Arterial Revascularization Therapies Study part II (ARTS II) Eur Heart J. 2007;28:433–442. doi: 10.1093/eurheartj/ehl539. [DOI] [PubMed] [Google Scholar]
- 4.Park T.K., Park Y.H., Song Y.B., Oh J.H., Chun W.J., Kang G.H., et al. Long-term clinical outcomes of true and non-true bifurcation lesions according to medina classification- results from the COBIS (COronary BIfurcation Stent) II Registry. Circ J. 2015;79:1954–1962. doi: 10.1253/circj.CJ-15-0264. [DOI] [PubMed] [Google Scholar]
- 5.Chen X., Li X., Zhang J.J., Han Y., Kan J., Chen L., et al. 3-Year Outcomes of the DKCRUSH-V Trial Comparing DK Crush With Provisional Stenting for Left Main Bifurcation Lesions. JACC Cardiovasc Interv. 2019;12:1927–1937. doi: 10.1016/j.jcin.2019.04.056. [DOI] [PubMed] [Google Scholar]
- 6.Kan J., Zhang J.J., Sheiban I., Santoso T., Munawar M., Tresukosol D., et al. 3-year outcomes after 2-stent with provisional stenting for complex bifurcation lesions defined by DEFINITION Criteria. JACC Cardiovasc Interv. 2022;15:1310–1320. doi: 10.1016/j.jcin.2022.05.026. [DOI] [PubMed] [Google Scholar]
- 7.Mohamed M.O., Lamellas P., Roguin A., Oemrawsingh R.M., Ijsselmuiden A.J.J., Routledge H., et al. clinical outcomes of percutaneous coronary intervention for bifurcation lesions according to Medina classification. J Am Heart Assoc. 2022;11:e025459. doi: 10.1161/JAHA.122.025459. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Raber L., Mintz G.S., Koskinas K.C., Johnson T.W., Holm N.R., Onuma Y., et al. Clinical use of intracoronary imaging. Part 1: guidance and optimization of coronary interventions. An expert consensus document of the European Association of Percutaneous Cardiovascular Interventions. Eur Heart J. 2018;39:3281–3300. doi: 10.1093/eurheartj/ehy285. [DOI] [PubMed] [Google Scholar]
- 9.Takagi K., Nagoshi R., Kim B.K., Kim W., Kinoshita Y., Shite J., et al. Efficacy of coronary imaging on bifurcation intervention. Cardiovasc Interv Ther. 2021;36:54–66. doi: 10.1007/s12928-020-00701-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Murasato Y., Kinoshita Y., Yamawaki M., Shinke T., Otake H., Takeda Y., et al. Efficacy of kissing balloon inflation after provisional stenting in bifurcation lesions guided by intravascular ultrasound: short and midterm results of the J-REVERSE registry. EuroIntervention. 2016;11:e1237–e1248. doi: 10.4244/EIJV11I11A245. [DOI] [PubMed] [Google Scholar]
- 11.Okamura T., Nagoshi R., Fujimura T., Murasato Y., Yamawaki M., Ono S., et al. Impact of guidewire recrossing point into stent jailed side branch for optimal kissing balloon dilatation: core lab 3D optical coherence tomography analysis. EuroIntervention. 2018;13:e1785–e1793. doi: 10.4244/EIJ-D-17-00591. [DOI] [PubMed] [Google Scholar]
- 12.Watanabe Y., Murasato Y., Yamawaki M., Kinoshita Y., Okubo M., Yumoto K., et al. Proximal optimisation technique versus final kissing balloon inflation in coronary bifurcation lesions: the randomised, multicentre PROPOT trial. EuroIntervention. 2021;17:747–756. doi: 10.4244/EIJ-D-20-01386. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Murasato Y., Nishihara M., Mori T., Meno K., Shibao K., Takenaka K., et al. Feasibility and efficacy of an ultra-short side branch-dedicated balloon in coronary bifurcation stenting. EuroIntervention. 2021;17:e425–e432. doi: 10.4244/EIJ-D-20-00334. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Vergara R., Valenti R., Migliorini A., Ciabatti M., Grazia De Gregorio M., Taborchi G., et al. Clinical and angiographic outcomes comparison of patients with left main vs non-left main bifurcation lesions treated with percutaneous coronary intervention with second-generation drug-eluting stents. J Invasive Cardiol. 2018;30:443–446. [PubMed] [Google Scholar]
- 15.Kang J., Bruno F., Rhee T.M., De Luca L., Han J.K., de Filippo O., et al. Impact of clinical and lesion features on outcomes after percutaneous coronary intervention in bifurcation lesions. JACC Asia. 2022;2:607–618. doi: 10.1016/j.jacasi.2022.05.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Grodecki K., Opolski M.P., Staruch A.D., Michalowska A.M., Kepka C., Wolny R., et al. Comparison of computed tomography angiography versus invasive angiography to assess Medina classification in coronary bifurcations. Am J Cardiol. 2020;125:1479–1485. doi: 10.1016/j.amjcard.2020.02.026. [DOI] [PubMed] [Google Scholar]
- 17.Hildick-Smith D., Egred M., Banning A., Brunel P., Ferenc M., Hovasse T., et al. The European bifurcation club Left Main Coronary Stent study: a randomized comparison of stepwise provisional vs. systematic dual stenting strategies (EBC MAIN) Eur Heart J. 2021;42:3829–3839. doi: 10.1093/eurheartj/ehab283. [DOI] [PubMed] [Google Scholar]
- 18.Oviedo C., Maehara A., Mintz G.S., Araki H., Choi S.Y., Tsujita K., et al. Intravascular ultrasound classification of plaque distribution in left main coronary artery bifurcations: where is the plaque really located? Circ Cardiovasc Interv. 2010;3:105–112. doi: 10.1161/CIRCINTERVENTIONS.109.906016. [DOI] [PubMed] [Google Scholar]
- 19.Costa R.A., Feres F., Staico R., Abizaid A., Costa J.R., Jr., Siqueira D., et al. Vessel remodeling and plaque distribution in side branch of complex coronary bifurcation lesions: a grayscale intravascular ultrasound study. Int J Cardiovasc Imaging. 2013;29:1657–1666. doi: 10.1007/s10554-013-0263-1. [DOI] [PubMed] [Google Scholar]
- 20.Antoniadis A.P., Mortier P., Kassab G., Dubini G., Foin N., Murasato Y., et al. Biomechanical modeling to improve coronary artery bifurcation stenting: expert review document on techniques and clinical implementation. JACC Cardiovasc Interv. 2015;8:1281–1296. doi: 10.1016/j.jcin.2015.06.015. [DOI] [PubMed] [Google Scholar]
- 21.Ohya M., Kadota K., Tada T., Habara S., Shimada T., Amano H., et al. stent fracture after sirolimus-eluting stent implantation: 8-year clinical outcomes. Circ Cardiovasc Interv. 2015;8:e002664. doi: 10.1161/CIRCINTERVENTIONS.115.002664. [DOI] [PubMed] [Google Scholar]
- 22.Hildick-Smith D., Arunothayaraj S., Stankovic G., Chen S.L. Percutaneous coronary intervention of bifurcation lesions. EuroIntervention. 2022;18:e273–e291. doi: 10.4244/EIJ-D-21-01065. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Kim H.Y., Doh J.H., Lim H.S., Nam C.W., Shin E.S., Koo B.K., et al. Identification of coronary artery side branch supplying myocardial mass that may benefit from revascularization. JACC Cardiovasc Interv. 2017;10:571–581. doi: 10.1016/j.jcin.2016.11.033. [DOI] [PubMed] [Google Scholar]
- 24.Lee H.S., Kim U., Yang S., Murasato Y., Louvard Y., Song Y.B., et al. Physiological approach for coronary artery bifurcation disease: position statement by Korean, Japanese, and European bifurcation clubs. JACC Cardiovasc Interv. 2022;15:1297–1309. doi: 10.1016/j.jcin.2022.05.002. [DOI] [PubMed] [Google Scholar]
- 25.Brunel P., Martin G., Bressollette E., Leurent B., Banus Y. “Inverted” provisional T stenting, a new technique for Medina 0,0,1 coronary bifurcation lesions: feasibility and follow-up. EuroIntervention. 2010;5:814–820. doi: 10.4244/eijv5i7a136. [DOI] [PubMed] [Google Scholar]
- 26.Naganuma T., Chieffo A., Basavarajaiah S., Takagi K., Costopoulos C., Latib A., et al. Single-stent crossover technique from distal unprotected left main coronary artery to the left circumflex artery. Catheter Cardiovasc Interv. 2013;82:757–764. doi: 10.1002/ccd.24988. [DOI] [PubMed] [Google Scholar]
- 27.Rigatelli G., Zuin M., Baracca E., Galasso P., Carraro M., Mazza A., et al. Long-term clinical outcomes of isolated ostial left anterior descending disease treatment: ostial stenting versus left main cross-over stenting. Cardiovasc Revasc Med. 2019;20:1058–1062. doi: 10.1016/j.carrev.2019.01.030. [DOI] [PubMed] [Google Scholar]
- 28.Berland J., Lefevre T., Brenot P., Fajadet J., Motreff P., Guerin P., et al. DANUBIO - a new drug-eluting balloon for the treatment of side branches in bifurcation lesions: six-month angiographic follow-up results of the DEBSIDE trial. EuroIntervention. 2015;11:868–876. doi: 10.4244/EIJV11I8A177. [DOI] [PubMed] [Google Scholar]
- 29.Kleber F.X., Rittger H., Ludwig J., Schulz A., Mathey D.G., Boxberger M., et al. Drug eluting balloons as stand alone procedure for coronary bifurcational lesions: results of the randomized multicenter PEPCAD-BIF trial. Clin Res Cardiol. 2016;105:613–621. doi: 10.1007/s00392-015-0957-6. [DOI] [PubMed] [Google Scholar]
- 30.Vaquerizo B., Fernandez-Nofreiras E., Oategui I., Suarez de Lezo J., Rumoroso J.R., Martin P., et al. Second-generation drug-eluting balloon for ostial side branch lesions (001-bifurcations): mid-term clinical and angiographic results. J Interv Cardiol. 2016;29:285–292. doi: 10.1111/joic.12292. [DOI] [PubMed] [Google Scholar]
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