Treatment for bifurcation lesions include a provisional one stent strategy and a dedicated up-front two-stent approach. In the provisional one stent strategy, both the main vessel and side branch are wired and only the main vessel is intervened upon with a DES. Following stent insertion, the proximal optimization technique (POT) is used to ensure main vessel stent apposition in the relatively increased proximal vessel diameter and to facilitate a larger strut opening in the side branch to allow for guidewire exchange while minimizing carinal shift [15]. The provisional stent technique is usually successful without the need for a rescue stent in the side branch.

The provisional technique can be converted to a two-stent strategy with an additional stent in the side branch if there is a residual stenosis that can lead to significant ischemia, if there is compromised flow in the side branch or if there is side branch dissection. This can be achieved with T and small Protrusion (TAP) stenting, Culotte technique stenting or reverse Crush stenting [15]. In the TAP technique, the side branch stent protrudes completely into the carina to allow for full coverage of the carina. The Culotte technique provides complete coverage, as the side branch stent extends more fully into the main vessel. It is most appropriate for bifurcations with more shallow angles, although it may be limited by the number of times it requires rewiring [17]. In the reverse Crush technique, the second stent is deployed in the side branch, protruding 2–3 mm into the main vessel, followed by noncompliant inflation in the main vessel to flatten the side branch stent against the main vessel wall [18]. Routine kissing balloons should be used when two stents are inserted [3, 19]. Fig. 2 provides an illustration of the end formation of each of these techniques.

Fig. 2.

The final two stent conformation in bifurcation lesions based on approach. Crush: The first stent is placed in the side branch with protrusion into the main vessel. The protruding portion is ‘crushed’ against the wall by dilatation with a balloon with subsequent stent placement in the main vessel. The procedure is completed with a final kissing balloon. TAP: The first stent is placed in the main vessel followed by rewiring of the side branch and kissing balloon to open the ostium. Subsequently, the side branch stent is deployed with minimal protrusion and a final kissing balloon is performed. Culotte: The first stent is placed in the side branch with protrusion into the main vessel. The main vessel is rewired through the strut of the first stent. A second stent is then placed in the main vessel and finished with a final kissing balloon.

The 2011 ACC/AHA/SCAI guidelines and the EBC still recommend a provisional stenting technique for the majority of lesions [15, 20]. The 2021 ACC/AHA/SCAI guidelines did not comment on the optimal bifurcation stenting technique [21]. Notable landmark trials that have not shown any benefit of dedicated two-stent techniques include the Nordic Bifurcation Study, the British Bifurcation Coronary Study, the CACTUS (Coronary Bifurcations: Application of Crushing Technique using Sirolimus-eluting stents) study, and the Nordic-Baltic Bifurcation Study IV [22, 23, 24, 25]. A meta-analysis investigating differences between provisional stenting and up-front two-stent interventions found no benefit to the two-stent approach [26]. Additionally, a combined analysis of the Nordic Bifurcation Study and the British Bifurcation Coronary Study showed a lower 5-year survival as well as an increase in fluoroscopy time, contrast volume, and higher peri-procedural biomarkers in up-front two-stent interventions [27].

There may, however; be a role for an up-front two-stent approach in certain bifurcation lesions. The DEFINITION (Definitions and Impact of Complex Bifurcation Lesions on Clinical Outcomes After Percutaneous Coronary Intervention Using Drug-Eluting Stents) study proposed indications including a side branch with a diameter stenosis $>$70% and a lesion length of $>$10 mm or two minor criteria including moderate-severe calcification, multiple lesions, LAD-LCx bifurcation angle $>$70, main vessel diameter 2.5 mm, thrombus-containing lesions and main vessel length $>$25 mm. These criteria were validated in the initial cohort study. In a secondary analysis of lesions that met the complex criteria, the up-front two-stent approach had an overall lower incidence of major adverse cardiovascular events (MACE) and target lesion failure compared to provisional stenting [28].

These criteria were subsequently confirmed in the DEFINITION II RCT, which demonstrated a decrease in target lesion revascularization (TLR) and target vessel myocardial infarction (MI) in the two-stent cohort [29]. The study, however; did include mandatory angiography at 12 months which may have led to an increase in TLR at this time-point. Therefore, there were potentially more sub-clinical target lesion restenosis in the provisional cohort that were identified in the clinical trial that may otherwise not have been identified in clinical practice. Likewise, target vessel MI occurred in the provisional stent cohort mostly at the time of the index procedure and may be due to restrictive optimization of the side branch for provisional stenting dictated by the study protocol. Nevertheless, the DEFINITION studies provide a framework for a “lesion-specific” individual approach to a heterogenous group of bifurcation lesions that offers clinicians reasonable support for a dedicated two-stent technique.

In scenarios where the up-front two-stent technique is used, the crush techniques are preferable (Fig. 2) [30]. This recommendation is based on the DKCRUSH (Double Kissing Crush versus Provisional Stenting Technique for Treatment of Coronary Bifurcation Lesions) II trial, which showed superiority of the DK crush technique to provisional stenting in non-left main bifurcations [31]. While this study provides evidence that the DK Crush technique may be preferable, other derivations of the crush technique, including the Mini Crush technique, as well as the Culotte technique, Simultaneous Kissing Stents, V Stenting, T Stenting or TAP may also be considered in the appropriate clinical scenario (Fig. 2).

Currently, ESC guidelines recommend a two-stent approach if the scenario includes a large side branch with a long ostial side branch lesion or a distal left main (LM) bifurcation, or if difficulty is anticipated in accessing an important side branch after main branch stenting [32]. The European Bifurcation Club acknowledges a two-stent technique may benefit lesions involving a large and significantly diseased side branch [15].

Additional considerations need to be taken for LM bifurcation lesions as opposed to non-LM bifurcations. Specific considerations for LM bifurcations include the relatively large diameter of the vessel, the frequency of trifurcation lesions, and the atherosclerosis pattern which tends to be longitudinal and diffuse extending into both branches [33]. Perhaps the most relevant consideration is that the side branch is frequently the Left Circumflex artery (LCx), which is unique in its wide angulation and the relatively large amount of myocardium it supplies [33].

Due to these differences, several technical considerations need to be considered. First it is generally recommended to wire both branches before balloon dilatation for protection [33]. If LM coverage can be achieved with the same stent that is implanted in the Left Anterior Descending artery (LAD) or LCx, then the stent should be sized based on the diameter of the distal vessel and the POT should be used to achieve proper apposition within the LM [33]. The 13th and 14th consensus documents by the European Bifurcation Club also recommend the provisional technique for LM bifurcation disease that does not include both branches [33, 34]. If bail-out side branch stenting is needed, T-stent, TAP or Culotte stenting are preferred [33, 34].

If LM bifurcation disease involves both branches, the stent technique should depend on the coronary anatomy and the operator’s skill [33]. If an up-front two-stent strategy is pursued, evidence favors using the DK crush technique if technically feasible. This recommendation is based on the results of the DKCRUSH-III and DKCRUSH-V trials which showed the benefit of the DK crush technique for LM bifurcation stenting as compared to the Culotte technique and provisional strategy, respectively [35, 36]. Other recent trials have still shown the benefit of provisional stenting [37]. The proper approach to LM bifurcation stenting is not yet clearly defined and remains open for debate.

It is unclear if there is any role for dedicated devices in bifurcation lesions in the current era. Most notably, in 2015, there was a study using a Tryton Side Branch Stent, a bare-metal stent (BMS), that had inferior outcomes compared to provisional stenting [37]. Another tool that may be useful in the setting of bifurcation lesions is drug-eluting balloons (DEB). These devices can be incorporated into the single stent approach while still providing anti-restenosis drug delivery into side branches. They have been shown to provide acceptable rates of late lumen loss in management of side branch lesions [38]. A meta-analysis comparing DEB to traditional balloon angioplasty in the management of side branch lesions showed decreased rates of side branch lumen loss in the DEB arm [39]. Additionally, DEB may be efficacious in treatment of side branch stenosis in distal left main bifurcation disease [40]. Additional information on lesion-specific interventions, tips and management of complications can be found in the BifurcAID application [41]. Future studies in this field will hopefully determine which specific lesions dictate an up-front two-stent approach and the best two-stent technique to achieve success.

If PCI is elected for LMCAD revascularization, technical considerations include the use of intravascular imaging and functional assessments, the use of hemodynamic support and management of bifurcation lesions. IVUS can help determine anatomy, plaque configuration and distribution of bifurcations. Typically, an IVUS minimal luminal area 6 mm${}^2$ has been used as a cutoff for clinically significant left main disease, although a smaller cutoff may be needed for patients of Asian descent [21, 32, 52]. By comparison, optical coherence tomography (OCT) is of more limited utility for LMCAD, particularly ostial LMCAD, because this technology requires blood clearance through the use of contrast injection [21]. Pooled analysis shows IVUS-guided left main interventions have demonstrated a mortality benefit compared to ‘unguided’ PCI [53]. Fractional flow reserve (FFR) can also be helpful in determining which unprotected distal left main lesions warrant intervention. A cutoff of $>$0.80 has been shown to have similar outcomes in medically treated patients compared with revascularization [54].

Identifying anatomy is of particular concern in LMCAD given differences in PCI outcomes between ostial or body lesions compared to distal bifurcation lesions. Ostial and body lesions account for approximately one third of LMCAD [55]. These lesions have more favorable outcomes and a lower incidence of restenosis [56]. While single stent insertion into ostial lesions can be straightforward, care must be taken not to overextend stents by more than 2 millimeters into the aorta to allow for subsequent re-engagement into the LM artery [57]. The specialized double ostial flash balloon can aid interventionalists in providing complete coverage of the aorto-ostial interface while also keeping the lumen patent for re-engagement. Bifurcation lesions, by comparison, represent the majority of LMCAD, are more technically challenging, and are associated with worse outcomes [56, 58]. Specific considerations for left main bifurcation lesions have been previously described.

Another consideration is whether the use of hemodynamic support during LM PCI is warranted, especially in scenarios of acute coronary syndrome (ACS) where patients with LM culprit lesions are more likely to present in cardiogenic shock [59]. Briguori et al. [60] evaluated prophylactic use of an intra-aortic balloon pump (IABP) in elective unprotected LM disease undergoing PCI and showed that the IABP group had lower intraprocedural events. SCAI and the ACC/AHA recommend considering MCS in those patients with reduced EF, decompensated hemodynamics, or expected prolonged ischemic times due to the anatomy of the lesions and the need for atherectomy [61].

There is unanimous support by both cardiothoracic surgeons as well as cardiologists to deploy a Heart Team approach to determine the best strategy for coronary revascularization in an individual patient. This multidisciplinary team should consider the patient’s comorbidities, SYNTAX score, Society of Thoracic Surgery (STS) risk score and patient preferences to determine the best intervention in each clinical setting [43].

Calcium modification techniques such as specialized balloons, atherectomy, lithotripsy, and laser technology can improve stent deployment and outcomes (Table 2). Traditional balloon angioplasty can lead to coronary dissection or perforation if applied to calcified lesions because of the non-homogenous nature of calcific plaques. Ultra-high pressure noncompliant balloons have been developed that allow for more symmetrical expansion and small studies have shown that they provide a high degree of procedural success and low rates of perforation in calcified lesions [71, 72].

Cutting and scoring balloons have also been developed to break calcium as they expand. Cutting balloons are an older technology, and evidence to support its use is mixed as some studies have shown limited efficacy with higher rates of perforation [73, 74]. Scoring balloons are thought to be a safer option and enhance stent expansion compared to traditional balloon angioplasty with an acceptable side effect profile [75]. Both the ESC and ACC/AHA/SCAI offer limited guidance on the use of these technologies [21, 32].

Atherectomy can remove calcified plaque and aid in stent delivery and expansion. Presently there are two types of atherectomy devices available: rotational (RA) and orbital (OA) atherectomy. Rotational devices have been generally more studied. The ROTAXUS (Rotational Atherectomy Prior to TAXUS Stent Treatment for Complex Native Coronary Artery Disease) trial illustrated improved procedural success associated with RA compared to stenting without atherectomy but did not show any difference in 9 month outcomes [76]. OA devices were evaluated in the ORBIT II (Evaluate the Safety and Efficacy of OAS in Treating Severely Calcified Coronary Lesions) trial, which achieved its pre-specified safety and efficacy endpoints with sufficient freedom from 30 day MACE and low rates of residual stenosis [77, 78].

A systematic review and meta-analysis comparing OA and RA yielded similar results [79]. At this time the choice between which device to use should be based on user preference and institutional availability. Current recommendations by the ACC/AHA/SCAI suggest RA in scenarios of fibrotic or heavily calcified plaques to improve procedural success. However, new indications for use are currently being investigated. Lee et al. [80] advocates atherectomy use for severe coronary artery calcification (CAC) by angiography and further evaluation with IVUS and OCT for moderate CAC. Atherectomy should be used if CAC is greater than 270° and considered if CAC is 180°–270°. Additionally, calcium scoring systems using IVUS and OCT have been developed that can help predict stent under-expansion and may guide operators on when to perform atherectomy [81, 82]. Intravascular imaging also provides information on calcium length and thickness, which are predictive of procedural success and can guide operators on which tools may be most effective [83].

Laser atherectomy (ELCA) is another alternative for calcifications however early studies showed that it was inferior compared to balloon angioplasty alone [84, 85]. It may be helpful to treat lesions that lead to stent under-expansion that cannot be dilated with high-pressure balloons, however ELCA tends to be ineffective for severe calcification [21, 80]. The use of ELCA along with iodinated contrast injection for treatment of focal calcific lesions has also been described.

Intravascular lithotripsy is another contemporary option which uses pressure waves that fracture the intimal and medial wall calcium. The Disrupt-CAD III (Disrupt Coronary Artery Disease) trial proved that it is a safe and effective modality for intervening on calcium plaques. It should be noted however, that long-term safety and efficacy have yet to be determined and long-term outcomes from the initial trauma are unknown [86, 87].