Techniques and Evidence for Percutaneous Coronary Intervention for Coronary Bifurcation Lesions: An Ongoing Journey : Cardiology Discovery

Journal Logo

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

Techniques and Evidence for Percutaneous Coronary Intervention for Coronary Bifurcation Lesions: An Ongoing Journey

Han, Yaling*; Li, Yang

Author Information
doi: 10.1097/CD9.0000000000000075
  • Open

Coronary bifurcation lesion (CBL) is a narrowing of coronary artery adjacent to, and/or involving the origin of, a significant side branch. CBLs encompass a wide variety of anatomic subsets and clinical scenarios, from left-main bifurcation with a significant amount of myocardium at risk to a small branching lateral branch with a negligible amount of myocardium at risk. CBLs account for approximately 15% to 20% of all cases requiring percutaneous coronary intervention (PCI).[1]

Catheter-based therapies can be technically challenging in terms of adapting available devices and strategies to the anatomy to restore vessel patency while preserving the fractal geometry of the bifurcation itself. Often, PCI of a CBL is associated with a lower prevalence of procedural success and higher prevalence of complications, thrombosis, and restenosis, than PCI of a non-bifurcation. Thus, safe and efficacious treatment strategies for CBLs are important.

Considerable progress has been made in CBL treatment thanks to rapid development of stenting strategies/technologies, a new generation of antiplatelet agents, intravascular imaging and coronary physiology, as well as deeper understanding of the abnormal flow dynamics around bifurcated areas.[2,3] These developments have resulted in fewer adverse clinical outcomes. Here, we discuss techniques and evidence for PCI of CBLs.

Stenting strategies for CBLs

Several studies have demonstrated that a stepwise, layered, provisional stenting approach with bail-out side branch stenting is similar (or even superior) to the upfront 2-stent technique if treating a CBL. Recent studies have revealed comparable results with stepwise provisional and systematic dual-stenting in true left-main bifurcation lesions. Therefore, current guidelines and consensus statements recommend a provisional stenting strategy as first-line treatment for most CBLs except for those with complex anatomy and diffuse atherosclerotic involvement of the main vessel and side branch.[4]

The provisional stenting strategy emphasizes the versatility of this approach, which allows adjustment of the treatment plan according to CBL complexity. This strategy starts with stent implantation in 1 branch and implantation of a second stent in the other branch only if indicated.[5] In a review article of this issue, Choo and Gurupparan[6] (Cardiac Vascular Sentral Kuala Lumpur, Malaysia) describe the key steps of the provisional stenting approach. However, release of the main-vessel stent often causes side branch occlusion because of shifting of the main-branch plaque or a change in the location of the carina, which leads to potentially fatal arrhythmias and perioperative myocardial infarction. Several innovative approaches have been reported as strategies for active protection of side branches: jailed wire, jailed balloon, balloon-stent kissing, and jailed Corsair. However, these approaches yield more frequent restenosis and repeat revascularization at the ostium of the side branch. Drug-coated balloons (DCBs) are a novel treatment strategy for coronary artery disease. They are based on the rapid and homogenous transfer of antiproliferative drugs into the vessel wall during inflation of a single balloon containing a lipophilic matrix without use of permanent implants.[7] Combined use of a provisional stenting technique and DCB to treat true CBLs is very attractive, and might improve clinical outcomes.[8,9]

A provisional stenting strategy is the most common default strategy. Two-stent technique (eg, T-stenting, T and protrusion, crush technique, culotte, simultaneous kissing stents, V-stenting, and Y-stenting), which differ in the amount of metal protruding into the main branch, use of a first kissing balloon, and/or the choice of stenting the side branch as the first vessel, is preferred in certain subsets of complex CBLs. The goal of these 2-stent techniques is to provide maximal apposition to the vessel wall with effective drug delivery if drug-eluting stents are used. One of the most widely evaluated upfront 2-stent PCI technique for CBLs in recent times, the “double-kissing” (DK)-crush method, was found to elicit favorable results in a series of randomized clinical trials (DKCRUSH I to VII) upon comparison with provisional and other 2-stent technique for CBLs.[10] In a review article in this issue, Kwan and Lin[11] (Lenox Hill Hospital/Norwell Health, USA) evaluated all clinical trials and studies on DK crush. Specifically, DK crush was superior to classic crush (in the DKCRUSH-I trial) and to provisional stenting (in the DKCRUSH-II trial) in true non-left-main bifurcation lesions. DK crush was also superior to culotte (in the DKCRUSH-III trial) and provisional stenting (in the DKCRUSH-V trial) in unprotected left-main bifurcations. Moreover, DKCRUSH-IV, VI, and VII are trials investigating the functional results of DK crush.

Even though PCI has evolved with different techniques for CBLs, optimal treatment in each individual case is controversial due to the high anatomic complexity and specific morphology of each CBL. A better algorithm for risk stratification and treatment based on DEFINITION criteria is available.[12]

Intravascular imaging and coronary physiology of CBLs

Angiographic ambiguity in visualization of lesions due to overlapping of the main vessel and side branch can lead to suboptimal stent deployment in complex CBLs.[13,14] Intravascular imaging, including intravascular ultrasound (IVUS) and optical coherence tomography (OCT), can provide essential information during procedure planning to ascertain anatomy and lesion preparation to check wire positions and lesion coverage after stent implantation, and to evaluate final expansion of the stent and vessel, which leads to improvement in clinical outcome. In a review article, Leesar et al[15] (University of Alabama, USA) summarized the role of IVUS and OCT for assessment of stenosis and stent optimization, and discussed new insights into the role of IVUS- and OCT-guided stenting in patients with CBLs.

Studies have shown that IVUS-guided PCI of bifurcations might reduce major adverse cardiovascular events (MACEs). A multicenter study of bifurcation registries in South Korea showed, for the first time, that IVUS guidance during PCI of bifurcations might reduce 4-year mortality significantly compared with that using conventional angiography-guided PCI.[16] Reassuringly, Chen et al[17] clarified that IVUS use following systematic 2-stent techniques for CBLs, from the data of a propensity score-matched population, was associated with a reduction in stent thrombosis (particularly a reduction in late stent thrombosis) and resulted in a significant reduction of ST-elevation myocardial infarction. In addition, a meta-analysis from 5 studies involving 7830 patients with CBLs showed that IVUS-guided revascularization could reduce the incidence of MACEs in early follow-up and cardiac death in late follow-up compared with that using an angiography-guided revascularization strategy. The ongoing randomized DKCRUSH VIII trial will evaluate differences in efficacy and safety between IVUS-guided and angiography-guided DK-crush stenting in patients with complex CBLs according to DEFINITION criteria, thereby providing IVUS-derived criteria to define optimal DK-crush stenting for CBLs of high complexity.[13]

The advent of OCT has provided some unique advantages thanks to its very high resolution. OCT can generate automatically contoured luminal areas across the variable geometry of CBLs.[18] Thus, OCT is a promising guidance method for PCI of CBLs from planning the strategy, to guidance during PCI and, finally, checking the interventional result. Development of 3-dimensional (3D) OCT allows better evaluation of coronary anatomy (particularly of the side branch ostium that is difficult to visualize by 2D OCT) to further improve the value of this technique in guiding PCI in these patients.[19] European Trial on Optical Coherence Tomography Optimized Bifurcation Event Reduction (OCTOBER) is the first adequately powered clinical trial aimed to show if routine OCT-based guidance of stent implantation improves clinical outcomes compared with standard angiographic-guided implantation in CBLs.[20] The forthcoming results will provide more evidence for the role of OCT in complex CBLs.

Knowledge of how to achieve optimal flow dynamics in CBLs is increasing. Fractional flow reserve (FFR) can guide treatment strategy, simplify the procedure, and reduce unnecessary complex interventions. In the DKCRUSH-IV trial, changes in side branch FFR were compared between patients undergoing DK crush versus provisional stenting for true CBLs.[21] The DKCRUSH-VI trial showed that angiographic guidance and FFR-based guidance of provisional stenting of true CBLs provided similar clinical outcomes at 1 year.[22] The DKCRUSH-VII trial found that a post-PCI FFR ≤0.88 predicted a higher incidence of target-vessel failure through 3-year clinical follow-up.[23]

Taken together, a compelling body of evidence has shown that use of intravascular imaging and coronary physiology during PCI for bifurcations leads to optimal stenting results and improves clinical outcomes. Researchers and interventional cardiologists may engage with these technological advances to provide more robust data on identifying clinically important strategies.

Dual antiplatelet therapy (DAPT) for PCI of bifurcations

The optimal duration of DAPT (defined as aspirin plus a P2Y12 inhibitor) in the setting of PCI for bifurcations to maintain the subtle balance between ischemia and bleeding risk is a challenge for physicians. In the Combined Insights From the Unified RAIN and COBIS bifurcation registries (BIFURCAT) encompassing 5537 patients, extended DAPT (>12 months) was associated with a lower incidence of MACEs compared with that using standard DAPT (6–12 months), driven by a reduction of all-cause death in patients with acute coronary syndrome (ACS) but not in patients with chronic coronary syndrome (CCS) after a median follow-up of 2.1 years.[24] Similarly, MACEs occurred less frequently in the extended DAPT group as compared with those in the short-DAPT (<6 months) group and standard DAPT group in ACS patients and CCS patients in the Euro Bifurcation Club registry,[25] as well as in the Korean Multicenter Angioplasty Team (KOMATE) registry and Korean Coronary Bifurcation Stenting (COBIS) registry.[26] Most studies have advocated use of extended DAPT in such high-risk patients because it has been shown to reduce ischemic events compared with standard DAPT. With regard to the choice of P2Y12 inhibitor while treating a patient using PCI for bifurcations, use of potent inhibitors instead of clopidogrel could mitigate ischemia risks. However, the beneficial effect of extended DAPT and use of a potent P2Y12 inhibitor in reducing the risk of MACEs seems to be coupled with an increased risk of bleeding (especially in patients with a high risk of bleeding). Therefore, carrying out large randomized trials, targeting specifically patients undergoing PCI for bifurcations and comparing short-term versus long-term DAPT regimens as well as the use of potent P2Y12 inhibitors, seems necessary.

CBLs remain fascinating and challenging subsets of lesions in interventional cardiology. In this issue, a clinical research article by Sheiban et al[3] (P. Pederzoli Hospital, Italy) and a meta-analysis by Kan et al[27] (Nanjing First Hospital, China) note that the broad anatomic spectrum and pathologic spectrum of CBLs are responsible for the complexity of these lesions. These articles reflect the discovery and advances in CBL intervention.

PCI methods for bifurcations have evolved substantially in the last decade, thereby resulting in improvements in CBL management. Guidelines for clinical practice are crucial to improve the procedural quality and clinical outcome, and continue to evolve owing to the rapidly changing landscape of therapeutic options.[28] The Chinese Society of Cardiology have published the first guideline on percutaneous treatment for coronary left-main bifurcation lesions to optimize procedural outcomes in patients with CBLs in China.[29] However, treatment of CBLs is controversial, and multiple technical strategies have been proposed. Nevertheless, continuous refinement of stenting techniques and accumulation of related evidence of bifurcations represent a major clinical need. Tailoring a strategy based on CBL anatomy and patient characteristics will have a greater role in future routine clinical practice.

Funding

None.

Conflicts of interest

None.

Editor note: Yaling Han is the Editor-in-Chief of Cardiology Discovery. The article was subject to the journal’s standard procedures, with peer review handled independently by this editor and her research groups.

References

[1]. Lunardi M, Louvard Y, Lefèvre T, et al. Definitions and standardized endpoints for treatment of coronary bifurcations. J Am Coll Cardiol. 2022;80(1):63–88. doi:10.1016/j.jacc.2022.04.024.
[2]. Taylor DJ, Feher J, Halliday I, et al. Refining our understanding of the flow through coronary artery branches; revisiting Murray’s law in human epicardial coronary arteries. Front Physiol. 2022;13:871912. doi:10.3389/fphys.2022.871912.
[3]. Sheiban I, Figini F, Gaspartto V, et al. Impact of coronary chronic total occlusion on long-term clinical outcome in patients with unprotected left main disease undergoing percutaneous coronary intervention. Cardiol Discov. 2022;2(3):145–151. doi:10.1097/CD9.0000000000000071
[4]. Burzotta F, Lassen JF, Louvard Y, et al. European Bifurcation Club white paper on stenting techniques for patients with bifurcated coronary artery lesions. Catheter Cardiovasc Interv. 2020;96(5):1067–1079. doi:10.1002/ccd.29071.
[5]. Hildick-Smith D, Egred M, Banning A, 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(37):3829–3839. doi:10.1093/eurheartj/ehab283.
[6]. Choo GH, Gurupparan K. Provisional stenting: a contemporary relook at the strategy and lingering issues. Cardiol Discov. 2022;2(3):191–196. doi:10.1097/CD9.0000000000000064.
[7]. Jeger RV, Eccleshall S, Wan Ahmad WA, et al. Drug-coated balloons for coronary artery disease: third report of the international DCB consensus group. JACC Cardiovasc Interv. 2020;13(12):1391–1402. doi:10.1016/j.jcin.2020.02.043.
[8]. Gao XF, Ge Z, Kan J, et al. Rationale and design for comparison of non-compliant balloon with drug-coating balloon angioplasty for side branch after provisional stenting for patients with true coronary bifurcation lesions: a prospective, multicentre and randomised DCB-BIF trial. BMJ Open. 2022;12(3):e052788. doi:10.1136/bmjopen-2021-052788.
[9]. Jing QM, Zhao X, Han YL, et al. A drug-eluting Balloon for the trEatment of coronarY bifurcatiON lesions in the side branch: a prospective multicenter ranDomized (BEYOND) clinical trial in China. Chin Med J (Engl). 2020;133(8):899–908. doi:10.1097/CM9.0000000000000743.
[10]. Vescovo GM, Chiabrando JG, Zivelonghi C, et al. Comparison of different stenting techniques in left main bifurcation disease: evidence from a network meta-analysis. J Invasive Cardiol. 2022;34(4):E334–E342.
[11]. Kwan TW, Lin P. A review of double kissing crush stenting in coronary bifurcation lesions. Cardiol Discov. 2022;2(3):174–181. doi:10.1097/CD9.0000000000000058.
[12]. Zhang JJ, Ye F, Xu K, et al. Multicentre, randomized comparison of two-stent and provisional stenting techniques in patients with complex coronary bifurcation lesions: the DEFINITION II trial. Eur Heart J. 2020;41(27):2523–2536. doi:10.1093/eurheartj/ehaa543.
[13]. Ge Z, Kan J, Gao XF, et al. Comparison of intravascular ultrasound-guided with angiography-guided double kissing crush stenting for patients with complex coronary bifurcation lesions: rationale and design of a prospective, randomized, and multicenter DKCRUSH VIII trial. Am Heart J. 2021;234:101–110. doi:10.1016/j.ahj.2021.01.011.
[14]. Zhang J, Gao X, Kan J, et al. Intravascular ultrasound versus angiography-guided drug-eluting stent implantation: the ULTIMATE trial. J Am Coll Cardiol. 2018;72(24):3126–3137. doi:10.1016/j.jacc.2018.09.013.
[15]. Leesar MA, Mering GOV, Jneid H. New insights into intravascular imaging of coronary bifurcation lesions and left main stenosis: what have we accomplished? Cardiol Discov. 2022;2(3):182–190. doi:10.1097/CD9.0000000000000069.
[16]. Kim SH, Kim YH, Kang SJ, et al. Long-term outcomes of intravascular ultrasound-guided stenting in coronary bifurcation lesions. Am J Cardiol. 2010;106(5):612–618. doi:10.1016/j.amjcard.2010.04.016.
[17]. Chen SL, Ye F, Zhang JJ, et al. Intravascular ultrasound-guided systematic two-stent techniques for coronary bifurcation lesions and reduced late stent thrombosis. Catheter Cardiovasc Interv. 2013;81(3):456–463. doi:10.1002/ccd.24601.
[18]. Wolfrum M, De Maria GL, Banning AP. Optical coherence tomography to guide percutaneous treatment of coronary bifurcation disease. Expert Rev Cardiovasc Ther. 2017;15(9):705–713. doi:10.1080/14779072.2017.1362982.
[19]. Miyazaki Y, Muramatsu T, Asano T, et al. Online three-dimensional OFDI-guided versus angiography-guided PCI in bifurcation lesions: design and rationale of the randomised OPTIMUM trial. EuroIntervention. 2021;16(16):1333–1341. doi:10.4244/eij-d-18-00902.
[20]. Holm NR, Andreasen LN, Walsh S, et al. Rational and design of the European randomized optical coherence tomography optimized bifurcation event reduction trial (OCTOBER). Am Heart J. 2018;205:97–109. doi:10.1016/j.ahj.2018.08.003.
[21]. Ye F, Chen SL, Zhang JJ, et al. Hemodynamic changes of fractional flow reserve after double kissing crush and provisional stenting technique for true bifurcation lesions. Chin Med J (Engl). 2012;125(15):2658–2662.
[22]. Chen SL, Ye F, Zhang JJ, et al. Randomized comparison of FFR-guided and angiography-guided provisional stenting of true coronary bifurcation lesions: the DKCRUSH-VI trial (Double Kissing Crush Versus Provisional Stenting Technique for Treatment of Coronary Bifurcation Lesions VI). JACC Cardiovasc Interv. 2015;8(4):536–546. doi:10.1016/j.jcin.2014.12.221.
[23]. Li SJ, Ge Z, Kan J, et al. Cutoff value and long-term prediction of clinical events by FFR measured immediately after implantation of a drug-eluting stent in patients with coronary artery disease: 1- to 3-year results from the DKCRUSH VII registry study. JACC Cardiovasc Interv. 2017;10(10):986–995. doi:10.1016/j.jcin.2017.02.012.
[24]. De Filippo O, Kang J, Bruno F, et al. Benefit of extended dual antiplatelet therapy duration in acute coronary syndrome patients treated with drug eluting stents for coronary bifurcation lesions (from the BIFURCAT registry). Am J Cardiol. 2021;156:16–23. doi:10.1016/j.amjcard.2021.07.005.
[25]. Cirillo P, Serafino L DI, Gamra H, et al. Impact of dual antiplatelet therapy duration on clinical outcome after coronary bifurcation stenting: results from the Euro Bifurcation Club registry. Panminerva Med. 2022. doi:10.23736/S0031-0808.22.04604-3. Online ahead of print.
[26]. Cho S, Kim JS, Kang TS, et al. Long-term efficacy of extended dual antiplatelet therapy after left main coronary artery bifurcation stenting. Am J Cardiol. 2020;125(3):320–327. doi:10.1016/j.amjcard.2019.10.046.
[27]. Kan J, Luo S, Wang D, et al. Impact of side branch lesion length on clinical outcome after coronary stenting techniques in patients with coronary artery bifurcation disease: a meta-analysis. Cardiol Discov. 2022;2(3):157–173. doi:10.1097/CD9.0000000000000066.
[28]. Rab T, Sheiban I, Louvard Y, et al. Current Interventions for the left main bifurcation. JACC Cardiovasc Interv. 2017;10(9):849–865. doi:10.1016/j.jcin.2017.02.037.
[29]. Chinese Society of Cardiology, Chinese Medical Association; Editorial Board of Chinese Journal of Cardiology. Chinese guideline for percutaneous coronary intervention in patients with left main bifurcation disease. Cardiol Discov. 2022;2(3):134–144. doi:10.1097/CD9.0000000000000074.
Copyright © 2022 The Chinese Medical Association, published by Wolters Kluwer Health, Inc.