Coronary left main (LM) disease is defined as the presence of a lesion leading to stenosis of ≥50% luminal diameter. About 2.5% to 10.0% of all lesions in coronary angiography are LM lesions, with 80% of LM disease involving the distal bifurcated vessels including the left anterior descending artery (LAD) and left circumflex (LCX). Another variant of LM disease is equivalent LM disease, indicated by the proximal location but without involvement of the ostium of lesions with a diameter stenosis of ≥70%, which are simultaneously localized proximal to the first diagonal or first obtuse marginal. Minimally, 75% of the left ventricular myocardium is supplied by the LM tree; therefore, increased death rate is higher in patients with LM disease, and suboptimal procedures using implantation of a drug-eluting stent (DES) is also commonly associated with frequently worse clinical events.
In the last several decades, significant developments in diagnosis and revascularization for patients with LM disease have been achieved. The 2018 European Society of Cardiology (ESC) and European Association for Cardio-Thoracic Surgery (EACTS) Guidelines made more modifications on percutaneous coronary intervention (PCI) for LM PCI. For 20 years, PCI using DES implantation has been used for the rescue of patients with LM disease in China, with early released data showing acceptable clinical results.[4–6] Recently, several randomized clinical trials in China have been completed and have provided convincing evidence favoring the improvements in short- and long-term clinical results by intravascular imaging-guided PCI.[7–12] Based on those exciting developments in engineering, materials, imaging modalities, new generation of medication (particularly antiplatelet agents), and stenting techniques, the Chinese Society of Cardiology (CSC) initialized the first guideline by interventional cardiologists from all across China for interventional treatment of LM disease. The writing committee of this guideline comprises members from 3 working groups, namely clinical research, intravascular imaging and physiology, and interventional cardiology. Members of this Task Force were selected by the CSC, and they undertook a comprehensive review of the published evidence for the diagnosis, treatment, and/or prognosis assessment of LM bifurcation lesions according to the CSC policy and estimation of expected health outcomes, where available data existed.
The level of evidence and strength of recommendation of particular treatment options were weighed and graded according to predefined scales, as outlined in Tables 1 and 2.
Table 1 -
Classes of recommendations.
|Class of recommendation
||Evidence and/or general agreements that a given treatment or procedure is beneficial, useful, and effective
||Have to be recommended
||Existence of conflicting evidence and/or divergent opinions about the usefulness/efficacy of a given treatment/procedure
| Class IIa
||Weight of evidence/opinion is in favor of usefulness or efficacy
||Should be considered
| Class IIb
||Usefulness/efficacy is less well established by evidence/opinions
||May be considered
||Evidence or general agreement that the given treatment or procedure is not useful/effective, and in some patients may be harmful
||Is not recommended
Table 2 -
Level of evidence.
|Level of evidence
|Level of evidence A
||Data derived from multiple randomized clinical trials or meta-analyses
|Level of evidence B
||Data derived from a single randomized clinical trial or large non-randomized studies
|Level of evidence C
||Consensus of opinion of the experts and/or small studies, retrospective studies, and registries
General description of LM bifurcation lesions
Anatomic features of LM lesions
LM originates directly from the left coronary sinus and is thus more clearly visible from a few particular views by angiography. Different to other coronary branches (ie, LAD, LCX, and the right coronary artery), rich elastic fibers and smooth muscle cells in the media of the LM trunk serve 2 contradictory effects: buffering the impact force of upstream blood flow (from the aorta) at high speed to downstream branches, thus minimizing the occurrence of mechanical injury to vessels distal to the LM; and prone to negative remodeling upon stimulus. Anatomically, LM is relatively short in length and has a large caliber and wider distal bifurcation angle (formed by the LAD and LCX) with unexpected abnormal blood flow and subsequent variant shear stress, a trigger for atherosclerotic development.
According to the plaque locations, LM disease is classified into 5 groups: isolated ostial disease (defined as a lesion within 3 mm from the ostium of the LM); isolated body/shaft disease (indicating the lesion is localized at the mid-shaft of the LM, usually 3–8 mm in length); distal disease (defined as a lesion located distal to the LM shaft but proximal to the ostial LAD or LCX, usually 5 mm in length), without involvement of the ostium of both branches; distal bifurcation lesions (defined as a distal lesion extending to involve the ostium of the LAD and/or LCX); and whole LM disease indicating LM involvement from the ostium to bifurcation. Acute LM occlusion is seen in patients with ST-segment elevation myocardial infarction (STEMI) or induced by guiding catheter, guide wires, and/or balloon inflation during the PCI procedure. Chronic LM occlusion is defined as total occlusion starting from the ostium or just 1 to 3 mm after the ostium of the LM, in which well-developed collaterals from the right coronary artery are life-saving for patients. Further, depending on the sources of the collaterals, LM disease is sub-grouped as follows: completely protected LM disease (wherein collaterals originate from the coronary artery itself or from 1 or more patent grafts), partially protected LM disease (collaterals only perfuse either the LAD or the LCX), and unprotected LM disease (no self-collateral or patent grafts at all).
Risk scoring systems for stratification and classifications
Both anatomic characteristics of LM and clinical variables are determinants of clinical outcomes after stenting LM. Different stratifications are summarized in Table 3.[14–19]
Table 3 -
Risk scoring systems for stratification.
||Class of recommendation
||Level of evidence
|Assessment of lesions’ complexity and strategy selection based on already accepted scoring systems[14–16]
|DEFINITION criteria differentiate simple from complex bifurcation lesions and guide the selection of stenting techniques[15,16]
|Using a combination of anatomical and clinical variables (ie, NERS II or SYNTAX II) to stratify patients, guide the stenting selection, and predict clinical outcomes after left main stenting treatment[17–19]
NERS: New risk stratification; SYNTAX: Synergy between percutaneous coronary intervention with taxus and cardiac surgery.
The Medina classification is a simple and easy-to-understand and use classification system. Thus, almost all clinical studies use this classification system to report the percentage of true or false bifurcations. Briefly, the 3 vessel segments are numericized by “1” or “0” in a clockwise direction from the proximal main vessel (MV) to the distal MV and side branch (SB) according to the presence or absence of lesions with a diameter stenosis >50%: 1 = presence, 0 = absence. Subsequently, all bifurcation lesions can be classified by true bifurcation (Medina 1, 1, 1/0, 1, 1/1, 0, 1) or false bifurcation (Medina 1, 0, 0/1, 1, 0/0, 1, 0/0, 0, 1) lesions. However, Medina 1, 0, 1 is also treated as another type of false bifurcated lesions as it only involves ostial SB rather than the ostium of the MV. Obviously, the Medina classification only tells if there is a lesion around the bifurcation area; unfortunately, it could not integrate more important variables into 1 box which are correlated with the complications during PCI procedure and clinical outcome after stenting; for example, bifurcation angle, lesion length, vessel diameter, thrombolysis in myocardial infarction (TIMI) flow, exact distribution of plaques, and plaque characteristics (such as calcification, stable or unstable plaques, and thrombus-containing lesions).
DEFINITION criteria were created from 1550 patients with coronary bifurcation lesions and were validated in another external 3660 cohorts with varied bifurcated disease. DEFINITION criteria aim to differentiate simple from complex bifurcation lesions and help interventional cardiologists to select an appropriate technique (I, B).[15,16] It consists of 2 major (according to LM and non-LM bifurcation lesions) and 6 minor criteria, by which a complex bifurcation lesion is defined as the presence of 1 major criterion and any 2 minor criteria [Table 4].
Table 4 -
|General requirement for all lesions
Vessel diameter of the side branch: ≥2.5 mm
Lesion length in the side branch: ≥10 mm
Diameter stenosis of the side branch: ≥70% (distal LM bifurcation) or ≥90% (non-LM bifurcation)
Bifurcation angle of <45° or >70°
Lesion length in the main vessel: ≥25 mm
Vessel diameter in the main vessel: <2.5 mm
A recent meta-analysis demonstrated that SB lesion length ≥10 mm is an independent factor of stent failure after provisional stenting (PS).
Synergy between PCI with taxus and cardiac surgery (SYNTAX) and SYNTAX II scores
The SYNTAX score released in 2009 and is a scoring tool solely on the basis of anatomical variables. A modified SYNTAX II scoring system published in 2013 included 1 new anatomic variable (unprotected LM disease) and 6 clinical variables (age, creatinine clearance, left ventricular function, sex, chronic obstructive pulmonary disease, and peripheral arterial disease). Multiple clinical studies demonstrated the superiority of SYNTAX II scoring to traditional SYNTAX scoring in terms of mortality after LM stenting.[17,18] Since then, the SYNTAX score II 2020 is associated with increased capacity of predicting the 10-year all-cause mortality and 5-year major adverse cardiac events (MACE) among patients with LM disease and triple vessel disease.
New risk stratification (NERS) and NERS II scores
The NERS score was created by interventional cardiologists from China, which required the combination of clinical variables, angiographic variables, whether intravascular ultrasound (IVUS) was used, and use of stenting techniques from patients with LM disease. In a similar way, NERS II scoring system was modified from original NERS scores, and it contained 16 variables including 7 clinical and 9 angiographic variables. Based on the NERS II scores, a cut-off of 19 scores significantly increased the association with 1-year mortality in patients with LM bifurcation lesions who underwent DES implantation. The correlation of higher NERS II scores with clinical events after 1 year through 5 years has been analyzed in serial DKCRUSH trials.[7–12,15,16] Notably, patients with NERS II scores of minimum 19 had a higher rate of MACE or target lesion failure through the 5-year follow-up, because of stenting procedures in patients with LM distal bifurcation lesions as included in the DKCRUSH III and DKCRUSH V trials.[7–10]
Percutaneous interventional treatment for patients with LM disease, particular for LM distal bifurcation lesions, is technically challenging. The recommendation is that the primary operator is required to have at least 25 cases/per year [Table 5].[3,23,24] Patients with LM bifurcation lesions commonly have downstream complex lesions, needing mechanical circulatory support, and reduced left ventricular ejection fraction or renal function, for whom a multidisciplinary cooperation consisting of cardiac surgeons, anesthetists, imagological experts, and vascular surgeons is recommended.
Table 5 -
Multidisciplinary team in stenting left main bifurcation lesions.
||Class of recommendation
||Level of evidence
|Having a multidisciplinary team (deciding the stenting strategy, recognizing and treating complications, improving clinical results)[3,23]
|Yearly volume of stenting left main bifurcation lesions per primary operator > 25 cases
Strategies of revascularization for LM bifurcation lesions
Pretreatment and stent platform selection
Pretreatment using conventional non-compliant balloon is frequently required and safe, with the recognition that an inflation time of usually less than 20 seconds can avoid circulatory collapse. For calcified lesions, there are multiple choices to modifying rigid plaques, including cutting balloon, dual-wire balloon, intravascular lithotripsy, laser, and rotational atherectomy, depending on the calcification specificities. While pretreatment using a cutting balloon is effective for calcified lesions localizing within a LM segment, a calcified lesion in the LM is usually extended to either LAD or LCX, and hence, rotational atherectomy is much more commonly used. Two small-scale studies confirmed the safety and efficacy of rotational atherectomy for calcified LM disease,[25,26] and this debulking technique is also recommended in international guidelines or consensuses.[27,28] The presence of superficial calcification in bifurcated vessels (as seen in the LM distal bifurcated region) is associated with the underexpansion and malapposition of a DES; therefore, coronary bifurcation lesions with severe or superficial calcification are considered the indication for rotational atherectomy. The mechanisms underlying the rotational atherectomy for bifurcation lesions are multifactorial, including differential cutting effect, debulking calcified or fibrotic plaques, minimizing the plaque volume at the bifurcated area, lessening carina shift, without obvious impact on non-calcified plaques, or a disease-free carina. Another advantage of rotational atherectomy is the lower rate of dissection and SB occlusion. Thus, a jailed wire in the SB is not required. Debulking of a calcified plaque with subsequently increased vascular compliance by rotational atherectomy is the key aspect to increase the deliverability of a DES, magnify the stent expansion, and achieve greater apposition. If only for calcified LM, a burr with a diameter of ≥1.75 mm is recommended; however, stepwise rotational atherectomy starting from a small burr is a good choice to debulk calcified plaques in the proximal LAD or LCX. Rotational atherectomy for calcified LM lesions is rarely accompanied by slow flow and no-reflow because of nourish vascular beds. However, once slow or no-reflow occurs, the consequence is usually very dangerous. Hence, for patients with calcified LM disease at large plaque burden and with reduced left ventricular function, mechanical circulator support is always recommended before rotational atherectomy.
Selection of stent platform
LM diameter can be >6 mm; thus, multiple variables of a stent should be considered before the procedure: availability of overexpansion, longitudinal distortion, cell geometric patterns, and expandable size. Overexpansion easily induces cell expansion, polymer damage, and stent fracture, which are all predictors of worse clinical events. Longitudinal compromising is frequently reported when stenting the ostial LM, most commonly caused by guiding a catheter and/or balloon with an extremely larger profile after inflation. Cell expandability determines the selection of stenting techniques for LM bifurcation lesions: crushing technique is recommended for a stent with limited cell expandability, whereas more 2-stent approaches are recommended if a stent has a wider range of cell expandability. Bioresorbable scaffold (BRS) is not recommended in the LM, unless the LM lesion is focal and the LM diameter is within the diameter range of available BRS, under the guidance of intravascular imaging.
Classification for lesions’ complexity is recommended for selecting stenting techniques [Table 6].[3,7–12,15,16,33,34]
Table 6 -
Recommendation of stenting techniques.
||Class of recommendation
||Level of evidence
|Provisional stenting for false bifurcation[3,33]
|Provisional stenting for DEFINITION criteria-defined simple bifurcation lesions[16,34]
|DK crush stenting for DEFINITION criteria-defined complex bifurcation lesions[7–12,15]
PS is recommended for false bifurcation lesions (I, A).[3,33] A subgroup analysis from the EXCEL trial revealed that PS is comparable to 2-stent for distal LM lesions without involvement of ostial LAD and LCX. PS is also the recommended approach (IIa, B) for DEFINITION criteria-defined simple LM bifurcation lesions.[16,34]
A key application of the PS procedure is to prevent SB occlusion, especially when the visual estimation for risk prediction of SB occlusion in coronary bifurcation intervention (V-RESOLVE) score is ≥12. Jailed wire is the most popularly used technique to prevent SB occlusion and it serves as a roadmap for rewiring when SB is abruptly occluded. Jailed balloon is also an effective technique, but no data demonstrating the superiority of one over another is yet available. Diameter of the MV stent is adjusted according to distal MV reference; therefore, proximal optimization technique (POT) using a large balloon with a ratio of balloon/proximal vessel at 1:1 is always recommended to enlarge the proximal stent and improve apposition. Routine ballooning SB or kissing balloon inflation (KBI) after stenting MV does not improve clinical outcome.[36,37] The recommended criteria for treating SB after MV stenting are: SB TIMI flow <3, ≥type B dissection, or fractional flow reserve (FFR) in the SB <0.8. Distal rewiring is recommended, and the whole procedure can be completed with the following sequence: POT–ballooning SB–KBI–re-POT. PS does not always mean 1 stent; it could use the 2-stent technique depending on the required position: distally rewiring-T stenting or Culotte stenting, and proximally requiring-T and protrusion (TAP).
Culotte is a modified T-stent technique. The classic Culotte stenting is considered as PS-T technique since it was created during bare metal stent era and involves the implantation of a stent into a LM and then SB. Recent evidence has shown that the first vessel to be stented is usually considered the more important vessel (supplying large amount of myocardium or abrupt occlusion could lead to death), a vessel taking off at a large angle (not easily rewiring), and severely diseased vessel. Traditional culotte stenting requires the complete overlapping of 2 stents, and hence has some limitations: longer segment with 2 layers of metal, possibly a large gap between struts and original carina, not suitable for bifurcation lesions with a distal angle >70°, and the difference in vessel diameter between 2 daughter vessels is >1 mm. More recently, a chain of modified Culotte stenting has been proposed, mainly including mini-Culotte and double-kissing culotte (DK Mini-Culotte).[41,42] DK Mini-culotte for true bifurcation lesions is superior to PS in the reduction of target lesion revascularization (TLR)/target vessel revascularization (TVR) and SB restenosis, and the treatment effect of those 2 modified culotte stenting is comparable to other 2-stent techniques.[42,43] Nevertheless, randomized controlled trials are needed to warrant the efficacy of modified culotte stenting. The major difference of the DK Mini-culotte from traditional culotte is the introduction of mini-protrusion of the first stent and distal rewiring. Accordingly, one possible problem is the shifting from mini-culotte to crushing.
Traditional T stenting
This is the father of T stenting, and a simple process with great procedural success. However, the most important limitation of traditional T stenting is the uncontrollable protrusion of the SB stent: too short leaving a gap and too much leading to high risk of stent thrombosis (ST).[45,46] The gold standard indication for traditional T stenting is a distal bifurcation angle of >70°.
Classic crush stenting
Colombo et al reported the classical Crush stenting method in 2003, which aimed to prevent abrupt SB occlusion as seen in the PS procedure. Classical crush stenting requires a 7-F guiding catheter via the femoral approach, and it consists of predilation, stenting SB, stent crush, rewiring the SB, and KBI. Usually, protrusion into the MV of a SB stent is around 3 to 5 mm and recalls the importance of perfect apposition to minimize ST. The major concerns about the classical crush stenting include a mass of metals overlapping in the distal MV which increase the difficulty of rewiring SB and KBI, a large gap between SB stent and the carina which can easily distort the SB stent if rewiring from this gap. All those drawbacks by classical crush are correlated with the increase of in-stent restenosis (ISR) and ST.[48–50]
A modified classical crush stenting, proposing a short protrusion (1–2 mm) to improve the success of KBI via trans-radial approach using a 6-F guiding catheter.
DK crush stenting
DK and double crush, just as the name implies, includes 2 crush and KBI which markedly improve the success of KBI. The key elements of DK crush procedure are as follows: short protrusion of a SB stent (2–3 mm), optimizing SB stent using a short non-compliant balloon and complete crushing (also POT) using a large balloon, rewiring SB and first KBI, stenting MV, and POT followed by rewiring-KBI-rePOT.[34,54] In addition to increasing the success of KBI, DK crush significantly promotes the quality of KBI which is correlated with clinical outcome. DKCRUSH I study reported the reduction of 1-year MACE and ST by DK crush when compared with classical crush. One meta-analysis including 21 randomized clinical trials demonstrated a 30% of reduction in TLR between DK crush versus PS, T, TAP, classical crush, and Culotte stenting. Accordingly, evidence from serial DKCRUSH trials[7–10] and more recent findings from the DEFINITION II trial state that for true complex bifurcation lesions (independent of the lesion locations), DK crush stenting is recommended (I, A).
Use of intravascular imaging and physiological assessment
Intravascular imaging and physiologic assessment play a critical role in stenting bifurcation and LM disease. The general recommendation is showed in Table 7.[28,57–62]
Table 7 -
Recommendation of intravascular imaging in stenting LM bifurcation lesions.
||Class of recommendation
||Level of evidence
|IVUS assessment prior-, during, and post-PCI[57,58]
|Minimal lumen area >6.0 mm2 measured by IVUS is indication for deferring LM PCI[58,59]
|Optical coherence tomography is feasible for guiding LM bifurcation stenting
|Fractional flow reserve determines the treatment option for side branch[60–62]
IVUS: Intravascular ultrasound; LM: Left main; PCI: Percutaneous coronary intervention.
A body of evidence has confirmed the importance of IVUS in LM bifurcation stenting.[57,58] IVUS assessment is recommended from lesion preparation, guiding device selection, and assessing stent expansion (I, B). IVUS assessment prior to stenting for LM bifurcation lesions is important, but the risk of circulatory collapse should be borne in mind.
The globally accepted cut-off of LM minimal lumen area is 6.0 mm2,[58,59] which is different from the 4.5 mm2 reported by a Korean team. For minimal lumen area between 4.5 and 6.0 mm2, FFR is recommended.[58,59] The decision of stent diameter varies depending on measurements by IVUS: equal to lumen diameter or 0.8 of vessel diameter (from media to media). The selection of the stent length is usually equal to the lesion length measured by IVUS, but varies upon the angulation and tortuosity. The commonly recommended landing zones have a plaque burden <50%. The stent coverage of the entire LM could be considered when the length of the LM is less than 8 mm. Key parameters derived from IVUS for assessing stent expansion include complete coverage (no geographic miss), no dissection or thrombus formation, and maximal expansion. Under expansion of a stent is the most common cause correlated with stent failure. Quantitative measurements for assessing stent under expansion are minimal stent area (>5 mm2), symmetry index (>0.8), expansion index (>0.9), residual plaque burden at the edges (<50%), and location/length of dissection. After LM stenting, the cut-off of the minimal stent area may vary according to population, sex, and ethnicity. Korean researchers reported the minimal stent area <8 mm2 in the LM trunk, <7 mm2 at the polygon of confluence, <6 mm2 at the ostial LAD, and <5 mm2 at the ostium of LCX could predict 1-year MACE after LM bifurcation stenting, which are smaller than the respective reported values (10, 7, and 6 mm2) from the EXCEL trial that compared the treatment difference between PCI and CABG for LM disease. Repeat dilation using larger balloon at high pressure is the effective treatment to repair under expansion. Incomplete coverage and severe dissection (deeper-to-medium with a length >3 mm) are 2 indications for additional stents. The ongoing DKCRUSH VIII trial aimed to analyze the difference in 1-year target vessel failure after DK crush for all true complex bifurcations between IVUS- and angiography-guidance.
Severe malposition is defined as the distance between struts and vessel wall >200 µm, mainly induced by stents with an extremely small diameter. Acute minor malposition is common but its correlation with clinical events is unclear. However, acquired malposition is an independent factor of MACE and ST.
Optical coherence tomography (OCT)
Compared to IVUS, OCT has an increased resolution but weak penetration. For LM bifurcation stenting, OCT is used clinically and recommended (IIa, B), because of some advantages: quick scanning for acquisition of images (36 mm/s) to minimize the impact of cardiac cycle; more accurate analysis of plaque specificities (such as calcification, inflammatory filtration, new vessel); 3-D modeling allowing precise assessment and measurements; more accurate assessment for stent expansion, vascular injury, and complications (dissection and thrombus formation). The OCTOBER trial is ongoing and aims to identify the advantage of OCT-guided bifurcation stenting. OCT is not suitable for assessing ostial LM lesion and is contraindicated in patients with heart failure and/or renal dysfunction as a contrast agent is required.
FFR and its derivatives
FFR is the gold standard of physiological assessment of myocardial ischemia and is recommended to guide LM bifurcation stenting (IIa, B). Accurate measurements of FFR for a given diseased vessel is affected by some factors such as downstream lesion of LM; thus, the pressure wire should be positioned as distally as possible; location of downstream lesion (pressure wire should be placed) in the distal point of the normal vessel, and the normal FFR is set as 0.80); true bifurcation with a SB diameter stenosis >90% or SB-FFR <0.45 (a normal FFR for the MV is set as 0.85); true bifurcation lesion (involving both LAD and LCX), manual pullback is recommended and stenting a diseased segment with the largest pressure gradient is important to re-measure FFR. For the PS procedure, after stenting the MV, SB-FFR is the only parameter to guide the need for additional treatment for SB. However, the difficulty in managing a rigid pressure wire across into the SB is impossible (failure rate: 9%). There is no randomized trial reporting the advantage of routinely measured SB-FFR in LM bifurcation stenting.
There are some derivatives of FFR including quantitative FFR (QFR),[72–77] instantaneous wave-free ratio (iFR),[78–83] and computer tomography angiography-derived FFR (FFRCT).[84–86] All those are waiting for further clinical trials to confirm their diagnostic performance. Fortunately, researches on QFR are progressing rapidly and has been studied in large-scale clinical trial showing its specificity and importance in predicting clinical outcomes.
Drug-coating balloon (DCB)
DCB for treating bifurcation lesions has been introduced by consortiums from China, Asia Pacific region, and other international areas[87–90]; however, there is a paucity of clinical data strongly supporting the advantage of DCB over conventional ballooning during the PS procedure. Ballooning using a DCB for LM bifurcations is rarely used but commonly introduced for treatment of LM-ISR lesions with or without involvement of bifurcations.[91,92] There are 2 options when using DCB for bifurcation lesions: MV-DES plus SB-DCB or DCB for both MV and SB; both are not recommended for LM or LM bifurcation lesions.
Mechanical circulatory support
Patients with LM (particularly LM bifurcation lesions) disease are at high risk of circulatory collapse during the stenting procedure. Intra-aortic balloon pump (IABP) has been used for many years in China, extracorporeal membrane oxygenation (ECMO) is available in some centers, and Impella® (Abiomed, Danvers, Massachusetts, USA) is only available in a few centers. Thus, evidence-based data are not sufficient to support the routine use of IABP for LM bifurcation stenting in patients with reduced cardiac function.[93,94] Indications and intervention timing of mechanical circulatory support for LM bifurcation stenting need to be comprehensively considered in combination with hemodynamics, morbidities, anatomical characteristics, difficulty of stenting procedure, expected complications and treatment, and operator’s experiences. It is recommended to establish a multidisciplinary team consisting of cardiology, cardiovascular surgery, anesthesiology, and critical care medicine to comprehensively evaluate and formulate technical plans, including vascular access, anesthesia methods, timing of use, support conditions, weaning, and postoperative management, to standardize the application of mechanical circulatory support and reduce the incidence of device-related complications (I, C). IABP, Impella, and ECMO are recommended for patients with LM bifurcation lesions and unstable hemodynamics, performed by an experienced multidisciplinary team (IIa, C) [Table 8].[28,93,94]
Table 8 -
Recommendations of mechanical circulatory support in stenting LM bifurcation lesions.
||Class of recommendation
||Level of evidence
|Establishing a multidisciplinary team to assess the indications and protocols of mechanical circulatory support for LM bifurcation stenting[28,93,94]
|IABP, ECMO, and Impella are recommended for high risk LM bifurcation lesions, but the procedure itself should be implemented by an experienced team[93,94]
ECMO: Extracorporeal membrane oxygenation; IABP: Intra-aortic balloon pump; LM: Left main.
Dual antiplatelet therapy (DAPT) strategy after PCI for LM bifurcation stenting
DAPT strategy aims to balance the risks of bleeding and ischemia. For any patients with LM bifurcation lesions who undergo DES implantation, the recommendation is aspirin with any 1 of the P2Y12 receptor inhibitors, so long as no contraindications exist for DAPT: aspirin plus ticagrelor for patients with acute coronary syndrome (I, A); ticagrelor is still recommended for patients with chronic stable coronary heart disease at high risk of ischemia or functional test of platelet/CYP2C19 genome analysis confirming the high possibility of resistance to clopidogrel (IIa, B) [Table 9]. [95–98]
Table 9 -
DAPT with left main bifurcation who undergo stenting.
||Class of recommendation
||Level of evidence
|DAPT using aspirin with P2Y12 receptor inhibitor, ticagrelor for ACS patients
|For patients with chronic stable ischemia at high risk of ischemia or platelet functional test or if CYP2C19 genome analysis suspects the resistance to clopidogrel, ticagrelor is recommended
|DAPT duration of at least 12 months for all left main bifurcation stenting[95–98]
|For patients at high risk of ischemia (ACS, 2-stent, and thrombus-containing lesions), DAPT >12 months is recommended
|For patients at low-risk of ischemia and high risk of bleeding, the 2 recommendations are: DAPT for 6 months, or 3–6 months DAPT then monotherapy (using P2Y12 receptor inhibitor
ACS: Acute coronary syndrome; DAPT: Dual antiplatelet therapy.
The accurate DAPT duration after LM bifurcation stenting is unknown. Existing data support a DAPT duration of at least 12 months after LM stenting, aiming to reduce the occurrence of MACE.[96–98] Furthermore, post hoc analysis from the EXCEL trial still shows a high rate of ischemic events after a 3-year DAPT treatment (no difference after adjustment). GLOBAL LEADERS and TWILIGHT trials compared the shifting from DAPT to monotherapy using ticagrelor alone after PCI, but no conclusive information was obtained for LM bifurcation stenting.[100,101] The recommendation of DAPT strategy for LM bifurcation stenting is at least 12 months (IIa, B); if patients are at high risk of ischemia (ACS, 2-stent, and thrombus-containing lesions), DAPT >12 months is recommended (IIa, B). For patients at high risk of bleeding and low-risk of ischemia, de-escalation using 6-month DAPT or 3-month DAPT then shifting to monotherapy (IIa, B) is recommended.
Clinical follow-up and long-term management after LM bifurcation stenting
The rate of ISR after LM bifurcation stenting varies from 7% to 18% at 1-year follow-up, depending on the lesion’s complexity, co-morbidities, stenting techniques, and stent platform.[7,8,102] ISR in LM is risky as it can result in a large amount of jeopardized myocardium and leads to sudden death. Routine angiographic follow-up is not recommended as it does not predict the risk of acute events like ST, death, and myocardial infarction. As a result, a long-term follow-up and management plan after LM bifurcation stenting is crucial [Table 10],[102,103] based on which a thorough secondary prevention is the only way to improve clinical outcomes (I, C). Repeat angiography is performed mostly in patients who have symptoms or evidence of ischemia. For the occurrence of ISR, re-implantation of a DES or use of a DCB is optional[91,92]; however, for second times of LM-ISR with multivessel ISR, CABG is the only recommendation. IVUS or OCT definitely deserves improvements in clinical outcome for patients with restenotic lesions after LM bifurcation stenting.[104,105]
Table 10 -
Clinical follow-up and long-term management.
||Class of recommendation
||Level of evidence
|For patients with LM bifurcation stenting, a comprehensive long-term follow-up plan and secondary prevention is necessary[102,103]
This guideline summarizes more recent evidence from both national and international trials and hence thoroughly describes the anatomical features of LM; classifications and indications of LM bifurcations; and serious assessment prior-, during, and post-stenting procedures. Finally, the current guideline clearly makes recommendations on key issues correlating with LM bifurcation stenting [Figure 1]. Our goal is to frame the practice of interventional treatment for LM bifurcations, improve clinical outcomes of patients with LM disease, and subsequently maintain our national team standing at the cutting edge in this field.
Writing group members: Junjie Zhang (Nanjing First Hospital); Zhen Ge (Nanjing First Hospital); Yang Li (General Hospital of Northern Theater Command)
Core experts: Feng Cao (Second Medical Center of Chinese People’s Liberation Army General Hospital); Shaoliang Chen (Nanjing First Hospital); Lianglong Chen (Fujian Medical University Union Hospital, Fujian Medical University); Yaling Han (General Hospital of Northern Theater Command); Jingbo Hou (The Second Affiliated Hospital of Harbin Medical University); Yi Li (General Hospital of Northern Theater Command); Yue Li (The First Affiliated Hospital of Harbin Medical University); Chun Liang (Shanghai Changzheng Hospital, Naval Medical University); Bin Liu (The Second Affiliated Hospital of Jilin University); Haiwei Liu (General Hospital of Northern Theater Command); Jian Liu (Peking University People’s Hospital); Ling Tao (Xijing Hospital, Air Force Medical University); Yan Wang (Xiamen Cardiovascular Hospital Xiamen University); Shangyu Wen (Tianjin Fourth Central Hospital, Tianjin Medical University); Kai Xu (General Hospital of Northern Theater Command); Yuejin Yang (Fuwai Hospital, Chinese Academy of Medical Sciences); Yong Zeng (Beijing Anzhen Hospital, Capital Medical University)
Expert committee members: Jian An (Shanxi Cardiovascular Hospital); Hui Chen (Beijing Friendship Hospital, Capital Medical University); Lijuan Chen (The Second Hospital of Jilin University); Tao Chen (The Second Affiliated Hospital of Harbin Medical University); Xiahuan Chen (Peking University First Hospital); Yan Chen (Fuwai Central China Cardiovascular Hospital); Hongliang Cong (Tianjin Chest Hospital); Kefei Dou (Fuwai Hospital, Chinese Academy of Medical Sciences); Xin Du (Beijing Anzhen Hospital, Capital Medical University); Chuanyu Gao (Fuwai Central China Cardiovascular Hospital); Dasheng Gao (The First Affiliated Hospital of Bengbu Medical College); Zhan Gao (Fuwai Hospital, Chinese Academy of Medical Sciences); Fentang Gao (Gansu Provincial Hospital); Ning Guo (The First Affiliated Hospital of Xi’An Jiaotong University); Yong He (West China Hospital, Sichuan University); Yuquan He (China-Japan Union Hospital of Jilin University); Qinhua Jin (Second Medical Center of Chinese People’s Liberation Army General Hospital); Chongying Jin (Sir Run Shaw Hospital, College of Medicine, Zhejiang University); Chunjian Li (The First Affiliated Hospital of Nanjing Medical University); Jing Li (Fuwai Hospital, Chinese Academy of Medical Sciences); Feng Li (Huainan Oriental Hospital Group); Jing Li (General Hospital of Northern Theater Command); Fan Liu (The Second Hospital of Hebei Medical University); Jun Liu (The First Hospital of Hebei Medical University); Qinghua Lu (The Second Hospital of Shandong University); Bo Luan (The People’s Hospital of Liaoning Province); Lifu Miao (The First Hospital of Tsinghua University); Genshan Ma (Zhongda Hospital Southeast University); Daoquan Peng (Xiangya Second Hospital Central South University); Shubin Qiao (Fuwai Hospital, Chinese Academy of Medical Sciences); Jie Qian (Fuwai Hospital, Chinese Academy of Medical Sciences); Xuesong Qian (Zhangjiagang First People’s Hospital); Hong Qu (Xuancheng City Central Hospital); Chunguang Qiu (The First Affiliated Hospital of Zhengzhou University); Weiwei Quan (Ruijin Hospital, Medical College of Shanghai Jiaotong University); Chunli Shao (Fuwai Hospital, Chinese Academy of Medical Sciences); Yibing Shao (Qingdao Municipal Hospital); Difei Shen (Renmin Hospital of Wuhan University); Linghong Shen (Shanghai Chest Hospital); Yaoming Song (Xinqiao Hospital of Army Medical University); Shengxian Tu (Shanghai Jiaotong University); Lianmin Wang (Mudanjiang Cardiovascular Hospital); Ruxing Wang (Wuxi People’s Hospital, Nanjing Medical University); Yu Wang (China Resources Medical, Beijing Jiangong Hospital); Yupeng Wang (Peking University Third Hospital); Mingliang Wang (Putuo People’s Hospital, Tongji University School of Medicine); Zhengzhong Wang (Qingdao Municipal Hospital); Yawei Xu (Shanghai Tenth People’s Hospital Affiliated Tongji University); Chang Xu (Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology); Tan Xu (Xinyang Central Hospital); Yuzeng Xue (Liaocheng People’ Hospital); Hua Yan (Wuhan Asia Heart Hospital); Kang Yao (Zhongshan Hospital, Fudan University); Zhuhua Yao (Tianjin People’ Hospital); Da Yin (First Affiliated Hospital, Dalian Medical University); Yan Yan (Beijing Anzhen Hospital, Capital Medical University); Song Yang (Affiliated Yixing People’s Hospital, Jiangsu University); Xue Yu (Beijing Hospital); Fei Ye (Nanjing First Hospital); Tao Ye (Xiamen Cardiovascular Hospital); Ran Zhang (Second Medical Center of Chinese People’s Liberation Army General Hospital); Bin Zhang (Guangdong Provincial People’s Hospital); Heng Zhang (Bengbu Medical University Affiliated the First Hospital); Lihua Zhang (Peking Union Medical College Hospital); Lei Zhao (The Second Hospital of Jilin University); Binquan Zhou (Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University)
Conflicts of interest
Editor Note: Yaling Han is the Editor-in-Chief of Cardiology Discovery, Shaoliang Chen is an associate editor of Cardiology Discovery, Feng Cao and Yi Li are editorial members of Cardiology Discovery. The article was subject to the journal’s standard procedures, with peer review handled independently of these editors and their research group.
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