New Insights into Intravascular Imaging of Coronary Bifurcation Lesions and Left Main Stenosis: What Have We Accomplished? : Cardiology Discovery

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Special Issue for Coronary Bifurcation Lesions, Guest Editor, Shaoliang Chen: Hot Topics

New Insights into Intravascular Imaging of Coronary Bifurcation Lesions and Left Main Stenosis: What Have We Accomplished?

Leesar, Massoud A.1,*; Von Mering, Gregory O.1; Jneid, Hani2

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doi: 10.1097/CD9.0000000000000069
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Coronary bifurcation lesions (CBL) constitute 15% to 20% of all coronary interventions[1] and remain one of the most technically challenging lesions in interventional cardiology.[1–3] In the era of drug-eluting stents (DES), the 2 primary interventional strategies for stenting CBL include complex (main vessel (MV) and side branch (SB) stenting), and the simple (provisional) strategy—MV stenting with provisional SB stenting—is based on the severity of SB stenosis after MV stenting.[1–3]

According to the latest European Bifurcation Club (EBC) recommendation,[3] the provisional SB stenting strategy is considered the “standard” approach for treatment of a vast majority of bifurcation lesions. A recent meta-analysis of randomized trials of complex versus simple strategy in 3265 patients demonstrated that there was no difference in cardiac events, myocardial infarction, target lesion revascularization (TLR), or stent thrombosis (ST), but the provisional strategy was associated with a reduction in all-cause mortality at the long-term follow-up.[4] However, the results from Double Kissing (DK) Crush (DKCRUSH) trials have shown significant reductions in revascularization, myocardial infarction, or ST in patients with complex CBL.[5–7] The discrepancy in clinical outcomes between randomized trials and DKCRUSH trials may have been the result of differences in lesion complexity. Recently, the DEFINITION II (Definitions and impact of complEx biFurcation lesIons on clinical outcomes after percutaneous coronary intervention (PCI) using drug-eluting steNts) trial randomized 660 patients with complex CBL to the complex strategy (MV and SB stenting) or provisional stenting (MV stenting).[8] They reported that the rate of target lesion failure (TLF) such as due to cardiac death and myocardial infarction and TLR was lower at the 1-year follow-up among those randomized to the complex strategy. This was largely driven by increased target vessel myocardial infarction and clinically driven TLR in the provisional stenting group. In addition, at the 1-year follow-up, the incidence of cardiac death was not significantly different between the 2 groups.

Intravascular imaging including intravascular ultrasound (IVUS) and optical coherence tomography (OCT) plays a pivotal role in detecting suboptimal stenting results and improving the outcome of PCI. In this review, we discuss the impact of intravascular imaging on lesion assessment, stent optimization, and improving the outcomes of patients undergoing stenting for CBL and left main (LM) coronary stenosis. In addition, we discuss new insights into the role of IVUS- and OCT-guided stenting in patients with CBL and LM stenosis provided by the ongoing randomized trials.

The role of IVUS on stent optimization and clinical outcome in patients with CBL

Provisional stenting is generally accepted as the first-line treatment for CBL. Kissing balloon inflation (KBI) after MV stenting leads to reduction in SB stenosis and maintains patency of the SB. However, the impact of KBI on outcomes has recently been questioned, because it can lead to asymmetric proximal MV stent [Figure 1]. Bench testing of CBL has shown that SB dilation resulted in expansion of the SB ostium, but it compromised the MV stent lumen area.[9] Consistent with this finding, we also reported that SB dilation compromised the MV stent area [Figure 2].[10] However, while KBI improved the lumen of the MV stent, it resulted in asymmetrical stent expansion [Figure 2], which could increase the stain to the vessel wall and ultimately increase the risk of stent dissection. Alternatively, the proximal optimization technique (POT) was reported to dilate the stent from its proximal part to just proximal to the carina by using a short, oversized balloon [Figures 3 and 4].[1,2] The EBC recommended MV stenting with POT and provisional SB stenting as the primary approach for CBL.[3] POT involves the use of a short, oversized balloon for dilation at the proximal segment of the stent, which leads to stent apposition to the vessel wall before the SB wire exchange. This enables easier SB wire access and reduces stent strut distortion and malapposition. Several recent bench models of CBL have demonstrated that POT expands the proximal segment of the stent symmetrically and opens the SB struts.[11,12] During stenting, particularly when using the 2-stent strategy or repeat KBI (ie, provisional stenting), the first POT is easy to perform. However, the second POT after KBI should be performed with a short, oversized, non-compliant balloon, such that the distal tip of the balloon should be positioned proximal to the carina to prevent shifting of the carina to the SB.

Figure 1::
Representative IVUS images of a bifurcation lesion with KBI. (A) Coronary angiogram shows critical stenosis of the LAD (red arrow); (B) IVUS shows bifurcation of the LAD (LA = 2.8 mm2) and the diagonal; (C) After stenting, stenosis of the LAD significantly improved; (D) KBI of the LAD and diagonal; (E) After KBI, the LAD and diagonal showed wide patency; (F) IVUS shows that the stent is well expanded in the LAD, but the stent struts are not floating between the LAD and diagonal and are opposed to the vessel wall after KBI. In addition, IVUS shows that after KBI, the stent was asymmetrically expanded. Adapted from: Int J Cardiol 2015; 187: 48–57. doi: 10.1016/j.ijcard.2015.03.183.[ 1 ] IVUS: Intravascular ultrasound; KBI: Kissing balloon inflation; LA: Lumen area; LAD: Left anterior descending.
Figure 2::
MSA and stent symmetry index after MV stenting and KBI. (A) MSA in the proximal, bifurcation, and distal stent segments after MV stenting, SB dilation, and KBI. Notably, MSA significantly reduced after SB dilation in the bifurcation segment, which significantly improved after KBI; (B) SSI in the proximal, bifurcation, and distal stent segments after MV stenting, SB dilation, and KBI. The SSI was significantly lower after KBI versus after MV stenting in the bifurcation and proximal segments. Adapt from: JACC Cardiovasc Interv 2013; 6(9): 923–931. doi: 10.1016/j.jcin.2013.04.019.[ 10 ] KBI: Kissing balloon inflation; MSA: Minimal stent area; MV: Main vessel; SB: Side branch; SSI: Stent symmetry index.
Figure 3::
Representative IVUS images of a CBL that underwent stenting and POT. (A) Critical stenosis of the LAD at bifurcation (purple arrow); (B) IVUS of the LAD shows a lumen area of 2.3 mm2 at bifurcation with a patent diagonal; (C) After stenting the LAD and proximal optimization with a short and large balloon, there was stenosis at the ostial diagonal; (D) FFR of the diagonal was 0.85 (shown by red arrow in C); and (E) IVUS shows that the stent is well expanded (stent area = 8.6 mm2); in addition, the stent is symmetrically expanded with struts floating between the LAD and diagonal (red arrows). Adapted from: Int J Cardiol 2015; 187: 48–57. doi: 10.1016/j.ijcard.2015.03.183.[ 1 ] CBL: Coronary bifurcation lesion; FFR: Fractional flow reserve; IVUS: Intravascular ultrasound; LAD: Left anterior descending; POT: Proximal optimization technique.
Figure 4::
Schematic illustration of POT. (A) Coronary bifurcation lesion after main vessel stenting; (B) POT using a short balloon sized to the proximal vessel and inflated in the stented segment just proximal to the carina. Adapted from: Int J Cardiol 2015; 187: 48–57. doi: 10.1016/j.ijcard.2015.03.183.[ 1 ] POT: Proximal optimization technique.

We performed IVUS examinations of the MV at baseline, after MV stenting, and after POT.[13] We showed by IVUS that in the proximal and bifurcation segments, the minimum stent area (MSA) was significantly larger after POT versus MV stenting, and the percentages of stent symmetry index (SSI) were not significantly different after POT versus MV stenting [Figure 5]. In the distal segment, IVUS parameters and SSI were not significantly different after POT versus MV stenting. Of note, both techniques can be used in the same patient; after KBI, POT should be performed to resolve asymmetric expansion of the stent [Figure 6]. The clinical outcome of KBI versus POT is yet unknown. As recommended by the EBC, the POT strategy seems a preferred technique, because KBI expands the stent asymmetrically and may induce dissection in the SB requiring stenting of the SB.

Figure 5::
MSA and SSI. (A) Comparisons of MSA in the proximal, bifurcation, and distal stent segments after POT versus MV stenting. Notably, MSA was significantly larger after POT versus MV stenting in the proximal and bifurcation segments; (B) Comparisons of SSI in the proximal, bifurcation, and distal stent segments after POT versus MV stenting. The SSI was not significantly different after POT versus MV stenting in any of the segments. Adapt from: Circ Cardiovasc Interv 2017; 10(10): e005535. doi: 10.1161/CIRCINTERVENTIONS.117.005535.[ 13 ] MSA: Minimal stent area; MV: Main vessel; POT: Proximal optimization technique; SSI: Stent symmetry index.
Figure 6::
KBI and POT. (A) After MV stenting; (B) After side branch dilation which reduced the stent area and distorted the stent; (C) After KBI, the stent is now expanded asymmetrically; (D) The proximal edge of the stent is malapposed; and (E) After the POT stent is well expanded symmetrically. Adapted from: Int J Cardiol 2015; 187: 48–57. doi: 10.1016/j.ijcard.2015.03.183.[ 1 ] KBI: Kissing balloon inflation; MV: Main vessel; POT: Proximal optimization technique.

In a propensity-matched analysis of 487 patients undergoing PCI of non-LM bifurcations with DES and by predominantly using a single-stent strategy, an IVUS-guided PCI strategy was associated with larger post-stent lumen diameters in both the MV and SB than an angiography-guided PCI strategy.[14] Notably, IVUS- versus angiography-guided PCI significantly reduced death or myocardial infarction. A recently conducted large IVUS randomized trial—the ULTIMATE (Intravascular Ultrasound Guided Drug-eluting Stents Implantation in All-Comers Coronary Lesions, including patients with CBL) trial—showed that IVUS-guided PCI was associated with significantly lower rates of target vessel failure (TVF) and ST at the 3-year follow-up.[15] A recent meta-analysis of 7830 patients with CBL showed that the incidence of major adverse cardiac events (MACE) in the IVUS-guided strategy were lower than those in the angiography-guided strategy.[16]

The role of OCT on stent optimization and clinical outcome in patients with CBL

OCT is an intracoronary imaging device, which provides comprehensive imaging for the assessment and treatment of CBL. OCT can provide more accurate and detailed information on thrombus and dissection in the vessels than IVUS. Burzotta et al[17] conducted an OCT study in 55 patients with CBL. They found that the stent was malapposed commonly at the proximal stent edge, but they also found more tissue prolapse at the distal stent edge. Hariki et al[18] conducted an OCT study in 72 patients with CBL. They reported that the rate of uncovered struts was lower in patients who underwent KBI than in those who did not. Furthermore, the rate of thrombus in the SB ostium was lower in patients who underwent KBI versus those who did not. However, the clinical outcome of the above observation by OCT will need to be confirmed.

Several case reports have provided further insights into the feasibility of online visualization of the guidewire position in CBL. Recently, the OPTIMUM (Online 3-dimensional Optical Frequency Domain Imaging (3D-OFDI) to Optimize Bifurcation Stenting Using Ultimaster Stent) trial randomized 110 patients to either 3D-OFDI or angiography-guided PCI.[19] After MV stenting and POT, those randomized to the 3D-OFDI-guided strategy underwent 3D-OFDI-guided rewiring into the jailed side branch, while patients randomized to the angiography-guided strategy underwent rewiring using angiography. The results showed that the rate of incomplete stent apposition was significantly lower in the 3D-OFDI-guided strategy than in the angiography-guided strategy. They also showed that the rate of optimal distal strut rewiring was 54% at the first attempt in the OFDI-guidance group. This indicates that even after POT, the wiring position was not optimal in about 50% cases, and that increased to 100% after the third rewiring attempt. The implication of the above study is that 3D-OFDI-guided stenting significantly reduced the rate of overhanging struts at the SB ostium. It is worth noting that overhanging struts in the bifurcation can alter microcirculation and shear rate, which might increase the neointimal growth within the area of low shear stress.[20] A pathological study also demonstrated a higher rate of stent malapposition and late ST at the flow divider region of the carina.[21] Future trials are required to investigate the impact of the overhanging struts in the bifurcation segment.

Recently, the PROPOT (Proximal Optimization Technique vs. Final KBI in CBLs) trial randomized 120 patients with CBL to POT followed by SB dilation versus KBI after MV stenting.[22] OCT was performed at baseline, immediately after wire recrossing to the SB, and at the final procedure. They showed that the rate of malapposed struts did not differ between the groups. However, more procedures such as POT + SB dilation + re-POT were needed in the POT groups than the KBI group. The above study was small and the outcome of patients was not significantly different at the 1-year follow-up.

Finally, the OCT Optimized Bifurcation Event Reduction (OCTOBER) trial is an ongoing randomized multicenter trial to determine the superiority of OCT- versus angiography-guided stenting in 1200 patients with CBL.[23] The primary outcome will be the TVF defined as the composite of cardiac death, target lesion myocardial infarction, and ischemia-driven TLR. Based on the study design, stenting will be performed by the provisional SB or 2-stent techniques depending on the complexity of lesions determined by online OCT analysis. The OCT-guidance will be used to determine (1) lesion preparation; (2) lesion length; (3) reference vessel sizes; (4) lesion coverage; (5) percent stent expansion; (6) strut malapposition rate; and (7) guidewire positions. The results of the OCTOBER trial may help establish a new role for OCT as a routine tool for optimization of complex CBL.

The role of IVUS on stent optimization and clinical outcome in patients with LM stenosis

IVUS is an imaging modality for assessment of the vessel lumen and wall. The higher ultrasound penetration into the vessel wall as compared with light resulted in increased application of IVUS for the assessment of LM coronary artery than OCT. This indicates that IVUS is the preferred imaging modality for LM coronary lesions. After a cutoff point of minimum lumen area (MLA) ≤9.0 mm2 was proposed to determine significant LM stenosis,[24] a number of studies reported that the cut-point for LM MLA for significant stenosis is actually lower than that reported in previous studies. Indeed, an LM MLA of 6.0 mm2 was validated against fractional flow reserve (FFR).[25] Furthermore, this cutoff point was validated by the multicenter, prospective Spanish Working Group on Interventional Cardiology (LITRO) study in which there was no difference in the 2-year mortality among patients in whom LM revascularization was deferred versus those who underwent revascularization.[26] However, smaller LM MLA cutoff points between 4.8 and 4.5 mm2 have been validated with FFR in recent studies.[27,28] Given that these studies have been conducted in Asian populations, the results might not apply to other ethnic groups.[27,28] Overall, the consensus is that to defer revascularization of the LM coronary stenosis in patients with MLA is >6 mm2.

Kang et al[29] investigated the optimal IVUS MSA cutoff points for prediction of event rates after DES stenting of unprotected LM coronary stenosis. In this study, 403 patients who underwent single- or 2-stent strategies were screened by immediate post-stenting IVUS and 9-month follow-up angiography. MSA was measured in each of the 4 segments: ostial left anterior descending (LAD), ostial left circumflex (LCX), polygon of confluence (POC, confluence zone of LAD and LCX), and proximal LM above the POC. The best MSA criteria that predicted angiographic restenosis on a segmental basis were 5.0 mm2 for the LCX ostium; 6.3 mm2 for the LAD artery ostium; 7.2 mm2 for the POC, and 8.2 mm2 for the proximal LM above the POC [Figure 7]. They showed that post-stent under-expansion was an independent predictor of 2-year MACE, particularly repeat revascularization.

Figure 7::
Minimum stent area cutoff values for the prediction of angiographic in-stent restenosis on a segmental basis. (A) Standard criteria; and (B) Post-EXCEL criteria. LAD: Left anterior descending artery; LCX: left circumflex artery.

Based on the EXCEL trial results,[30] it has recently been suggested that for large people, higher post-stenting cutoffs should be applied in order to decrease TLR rates, that is, 9.8 mm2 (10) in LM, 7.3 mm2 (7) in LAD, and 5.7 mm2 (6) in LCx [Figure 7].

The Nordic-Baltic-British LM Revascularization (NOBLE) study is a prospective, randomized, open-label trial of 1201 patients with unprotected LM coronary artery stenosis treated with PCI versus CABG.[30] Of 603 patients treated by PCI, 435 (72%) underwent post-PCI IVUS assessment. At 5 years, the composite of MACE was not significantly different in patients who underwent post-PCI IVUS versus those who underwent angiography-guided stenting. However, TLR was significantly lower in the IVUS group than in the angiography-guided group. They concluded that reduction in TLR by IVUS would likely improve outcomes.

Recently, Kinnaird et al[31] investigated the use of intravascular imaging (IVUS and OCT) in patients undergoing PCI of the LM coronary artery stenosis. They used the British Cardiovascular Intervention Society database. Propensity matching was conducted in 5056 patients who had PCI of the LM coronary artery stenosis with and without intravascular imaging. They showed that the use of intravascular imaging resulted in a lower rate of complications, and improved 30-day and 12-month survival. They concluded that in their largest study to date, the use of intravascular imaging resulted in a 34% reduction in mortality among patients underwent stenting of the LM coronary artery stenosis.

Zhang et al[8] reported that the DKCRUSH technique compared with provisional stenting significantly reduced event rates in patients with CBL and complex distal LM stenosis. Recently, the ULTIMATE trial showed a significant reduction in event rates by IVUS-guided stenting in all patients, including patients with CBL.[15] However, the clinical outcomes of patients with complex bifurcation lesions after IVUS-guided DKCRUSH stenting versus angiography-guided stenting has never been studied in a randomized trial. In this respect, the ongoing randomized DKCRUSH VIII trial meeting the DEFINITION criteria will investigate the outcomes of the IVUS-guided versus angiography-guided DKCRUSH stenting among patients with complex bifurcation lesions.[32] In this study, 556 patients with complex LM or non-LM bifurcation lesions will be randomized to IVUS- versus angiography-guided DKCRUSH stenting. The primary end point of the study is to investigate the rate of 12-month TVF, defined as cardiac death, target vessel myocardial infarction, or clinically driven TVR. All patients will be followed-up for 3 years after the index procedure to investigate the long-term outcome. This study will also provide further insights into the optimal IVUS-guided DKCRUSH stenting among patients with CBL who meet the high complexity criteria.

The role of OCT on stent optimization in patients with LM stenosis

Acquiring OCT images of the LM trunk is challenging. In addition, imaging of the ostial lesions by OCT is impossible in principle, given the fact that the guiding catheter is engaged into the ostium of the LM trunk. Even if the guiding catheter is withdrawn from the ostium, image acquisition is difficult because of incomplete elimination of red blood cells. In the current European guidelines for myocardial revascularization, OCT is not considered for LM intervention, whereas IVUS is a class IIa recommendation for this indication.


Both IVUS and OCT have significantly improved the assessment of complex lesions in interventional cardiology. IVUS and OCT have proven to be valuable tools in cardiac catheterization laboratories in the era of contemporary interventional cardiology. In particular, IVUS has proven to be of utmost importance in complex coronary lesion subsets such as LM stenosis, ostial, and CBL. In these lesion subsets, IVUS provides significant insights for decision-making and to reduce the incidence of MACE.

To our knowledge, the clinical impact of IVUS for stent optimization in patients with complex CBL and LM coronary stenosis has not been investigated in a randomized trial. In this respect, the results of the DKCRUSH VIII trial will shed light on the superiority of the IVUS-guided versus angiography-guided DKCRUSH stenting in patients with CBL. Along the same lines, OCT has a promising role in stent optimization for CBL. The results of the OCTOBER trial will elucidate the role of OCT-guided stent optimization in patients with CBL. If the above randomized trials provide convincing evidence regarding the benefit of IVUS and OCT on the outcome of stent optimization, these data may serve as an impetus for changing clinical practice and upgrading IVUS and OCT to the class I recommendation.

The European expert consensus recommends the “upfront use of imaging” to fully assess the vessel wall morphology, degree of calcification, and lesion characteristics prior to stent implantation.[33] This will lead to upfront planning of the PCI strategy, including the need for additional lesion preparation or adjunctive treatment, and provide guidance for stent selection and optimization. Subsequent imaging examinations are needed to assess and optimize the stenting results. IVUS has been used since the 1990s and has therefore achieved greater penetration worldwide than OCT, which became commercially available only in the late 2000s. Both modalities are used based on the operators’ preferences. The major barriers to adoption of intravascular imaging are lack of adequate experience, extended procedure time, and catheter cost, but these are offset by improving outcomes.



Conflicts of interest



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Tomography; optical coherence; Intravascular ultrasound; Coronary interventions

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