In the past few decades, tremendous developments have been made in the field of interventional cardiology. The evolution of such tools as balloon angioplasty, bare-metal stents (BMS) and now drug-eluting stents (DES) has incrementally opened up new possibilities in the treatment of coronary artery disease and, correspondingly, an ever-decreasing need for invasive surgery. The most challenging area within the field of percutaneous coronary intervention (PCI) remains the treatment of unprotected left main stenosis (ULM) and bifurcation lesions. This short review will provide a glimpse of current developments in these two areas.
Unprotected Left Main Stenosis
ULM is by no means a rare occurrence. Between 2.5 and 10% of patients undergoing coronary angiography are found to have left main stenosis,1,2 with many also suffering from further atherosclerotic disease of the other epicardial arteries.2,3 Coronary artery bypass grafting (CABG) has been the traditional invasive strategy for such patients, but recent evidence is emerging to support the use of DES in combination with a percutaneous approach.
Assessing the Severity of Left Main Stenosis
The determination of the severity of left main stenosis needs to be accurate. This has obvious implications for the physician in the clinical decision-making process. It is accepted that coronary angiography – in particular by visual estimation – as a technique to estimate the severity of a stenosis is prone to error.4 In practice, two main modalities are used to quantify the severity of stenotic lesions: intra-coronary measurement of myocardial fractional flow reserve (FFR) and intravascular ultrasound (IVUS).
Myocardial FFR is calculated from the ratio of the mean distal coronary artery pressure and mean aortic pressure during maximal hyperaemia. An FFR <0.75 is functionally significant and correlates well with the presence of ischaemia-producing coronary artery stenotic lesions.5 A study performed by Bech et al. looked at the role of FFR measurements in deciding on CABG as a treatment for left main stenosis. They found that coronary-pressure-derived FFR correlates with inducible ischaemia caused by left main stenosis and that deferral of CABG was feasible when the FFR was >0.75.6
The advantage of IVUS over FFR is that, besides assessing the severity of the stenotic lesion, IVUS can also provide anatomical information such as vessel size, presence of calcification and extent of distal bifurcation involvement. Compared with angiography, IVUS is more sensitive at detecting early coronary atherosclerosis.7–9 Jasti et al. sought to harness both techniques. They identified an IVUS-determined minimum lumen diameter of 2.8mm and a minimum lumen area of 5.9mm2 as strong predictors of the physiological significance of left main stenosis. In patients with ambiguous left main stenosis, they found that an FFR of >0.75 was a strong predictor of event-free survival.10
Coronary Artery Bypass Grafting in Left Main Stem Revascularisation
The long-term outcomes and benefits of CABG in the management of left main coronary artery (LMCA) stenosis are well recognised.11 In the PCI guidelines written by the European Society for Cardiology (ESC), CABG remains the gold standard (if not the mainstay) treatment. Despite the overall improvement of CABG results in recent years – due in part to the increasing use of arterial conduits – this technique is still associated with significant peri- and post-operative death and morbidity. Nalysnyk et al. reviewed adverse events in 176 conventional CABG studies comprising 200,000 patients undergoing CABG between 1990 and 2001 and found that the average incidence of in-hospital death was 1.5%, non-fatal MI 2.4%, non-fatal stroke 1.3%, gastrointestinal bleeding 1.5% and renal failure 0.8%; 30-day mortality was 2.1%.12
Percutaneous Coronary Intervention for Left Main Stenosis
The advent of BMS opened up a new dimension in the treatment of ULM disease. Numerous studies have looked at the short- and long-term outcomes of using BMS. A total of six studies in 588 elective patients receiving BMS for ULM demonstrated an in-hospital mortality rate between 0 and 4%.3,13–17 The long-term follow-up – ranging from six to 31 months – showed a cardiac mortality rate of between 0.8 and 11.9%. Wong et al. reported excellent results in their study of 50 elective stenting procedures of ULM: 100% procedural success, no in-hospital cardiac events and a 20% recurrence rate of left main stenosis.17 Following these results, they concluded that PCI with BMS might be a safe alternative to CABG in ULM. However, with restenosis rates averaging around 20% – as evidenced in the Unprotected Left Main Trunk Investigation Multicenter Assessment (ULTIMA) registry18 – with potentially fatal outcomes, widespread use of BMS failed to gain much popularity.
As with BMS, the arrival of DES pushed the boundaries of interventional cardiology further. The use of DES has led to significant reductions in restenosis and target lesion revascularisation (TLR). DES is fast becoming the favoured percutaneous treatment modality for complex coronary lesions. A number of registries and non-randomised studies have demonstrated the effectiveness of DES for ULM, with no differences between paclitaxel- and sirolimus-eluting stents.19 Chieffo et al.20 performed elective DES implantation on a consecutive series of 85 patients with ULM, including patients in whom CABG was contraindicated. High mortality risk scores were present in 45% of the patient population (EuroSCORE >6 and/or Parsonnet >15). Six-month cardiac mortality rates and major adverse cardiac event (MACE)-free survival rates were 3.5 and 80%, respectively.
Lee et al.21 have recently published a non-randomised study comparing 50 DES patients with 123 consecutive CABG patients in the treatment of ULM. Forty-six per cent of the CABG group and 64% of the PCI group were deemed high-risk (Parsonnet score >15). Thirty-day mortality was lower in the PCI group (2 versus 5% for CABG), with six-month follow-up showing a non-significant advantage in the PCI group (96 versus 87% for CABG). In a recently published registry, Chieffo et al.22 evaluated outcomes of 147 patients with stenosis in the ostium and/or the mid-shaft of an ULM using DES. At a follow-up of 886±308 days, the MACE rate was 7.4% with a restenosis rate of only 0.9% (one patient).
At present, results from longer-term randomised comparisons between CABG and PCI using DES in the treatment of ULM are lacking. Until such studies conclusively show the benefits or non-inferiority of PCI, the interventional cardiologist – together with the patient and the surgeon – will need to make an informed decision based on the available clinical information.
Bifurcation lesions present a unique challenge to the interventional cardiologist. Besides the usual difficulties associated with stent placement, bifurcation lesions are further complicated by unique problems such as the plaque shift effect with compromise of the side branch. In 4.5–26% of cases,23–27 this plaque shift results in side branch occlusion that may require dilation or stenting.23
The increased turbulent blood flow in coronary bifurcations and the resultant shear stress predisposes to the development of atheromatous plaques. Several classification systems have been used to describe the spectrum of bifurcation lesions encountered. The Duke classification is based on the plaque location within the main vessel or side branch. Lefevre et al.28 classified bifurcation lesions based on their morphology and the angle of the side branch to the main vessel: Y-shaped lesions (side branch to main vessel angle <70º) or T-shaped lesions (side branch to main vessel angle >70º). The Medina Classification29 is also based on the location of the lesion. It uses a binary system, allocating 1 or 0 to indicate the presence or absence, respectively, of a lesion in the proximal or distal main vessel and side branch.
Treatment Strategies for Bifurcation Lesions Using Drug-eluting Stents
Treatment of bifurcation lesions can be broadly divided into two categories: simple stenting – consisting of stent implantation in the main branch and optional kissing balloon inflation or second stent insertion in the side branch – and complex stenting – involving stent implantation in both the main vessel and the side branch. Simple stenting strategies are usually used in situations where the side branch is small (<2mm) or has no or limited disease at the ostium.
When a simple/provisional strategy fails, and particularly when plaque shift or dissection occurs, the placement of one or more stents is required. Studies have shown that, when using BMS, placement of a second stent in the side branch has led to significantly higher rates of restenosis compared with single-stent strategies.24,25 Although the use of DES has greatly reduced this problem and improved outcomes, focal restenosis at the side branch ostium continues to be problematic.
The two main types of DES – Cypher (sirolimus) and Taxus (paclitaxel) stents – are widely used in the treatment of bifurcation lesions with good results. Pan et al.30 performed a randomised comparison looking at the benefits of using either type of stent in bifurcation lesions. They found that Cypher stents were associated with a lower main vessel restenosis rate, lower IVUS neointimal proliferation and a lower side branch restenosis rate. These results mirror a similar – albeit not randomised – comparative study in 2005, which showed a nine-month lower target vessel revascularisation rate.31 This advantage of Cypher stents is thought to be due to the greater inhibition of neointimal proliferation.30
There are four main complex techniques employed, with variable success: T-stenting, crush stenting, culotte stenting and simultaneous kissing stenting/V-stenting (SKS).
The T-stenting technique is a two-stage strategy.32 First, the main vessel is stented. A second guidewire is then introduced, crossing the metal struts of the first stent into the side branch, with the aim of deploying the second stent at the ostium of the side branch. This technique is best suited where the main vessel to side branch angle is >90°. An angle <70° is associated with either a too proximal deployment of the side branch stent – with protrusion of the stent into the main vessel – or a too distal deployment of the side branch stent – with incomplete coverage of the ostium and thus a higher risk of ostium restenosis.
Following stenting to the side branch with protrusion into the main vessel, the main stent is implanted, crushing the side branch stent. In the crush technique, the final step of kissing balloon dilatation is essential in terms of significantly reducing the long-term possibility of restenosis at the side branch ostium.33 The three layers of struts in the proximal part of the bifurcation near the side branch ostium provide a complete and firm coverage of the ostium while delivering maximum immunosuppressant effect (in DES). However, the increased rate of stent thrombosis with this technique remains a concern.
The culotte technique34 is suitable for most angles of bifurcation. This technique can be technically difficult and time-consuming. Although it provides complete stent coverage of the bifurcation, the high concentration of metalwork was associated with high rates of thrombosis and restenosis in the setting of BMS. With DES, there has been a resurgence of interest in the culotte technique. Comparing the culotte with the T-stenting technique, Kaplan et al.35 identified a higher residual diameter stenosis of the side branch ostium using the T-stenting technique versus culotte stenting (3.44±7.39% in the culotte group versus 12.55±11.47% in the T-stenting group; p<0.0001).
Simultaneous Kissing Stenting and V-stenting
The SKS technique36 is most suitable for easily assessable bifurcations with narrow bifurcation angles, large and relatively disease-free proximal main vessels and when both branches are of similar diameter. In the V-stenting technique, the proximal ends of both stents are positioned just at the carina of the bifurcation, abutting each other. Both techniques are completed with the kissing balloon inflation. Given the necessary physical conditions, the SKS and V-stenting techniques have rather limited applicability.
Simple versus Complex Strategies
It is widely accepted that both complete lesion coverage (especially at the side branch ostium) and achieving optimal stent apposition in all stented segments are critical in preventing focal restenosis, particularly at the side branch ostium;37 however, the recently published NORDIC Bifurcation study38 seemed to suggest that simple stenting was superior to complex stenting. This study randomised 413 patients with bifurcation lesions to one of two groups: simple stenting of the main vessel only (n=207) and complex stenting with stents in both the main vessel and the side branch (n=206). Of the latter group, 50% were treated by crush stenting, 21% by culotte stenting and 29% by a variety of techniques (predominantly T-stenting). Overall, only 2.7% of the patients randomised to the main vessel stenting arm received a stent in the side branch. Angiographic results at eight months showed no significant difference between the treatment strategies. Post-procedure minimum lumen diameter was increased in all parts of the bifurcation in the side-branch-stented patients, but this difference did not translate into a lower rate of restenosis at eight months. Two previous randomised studies (using DES) published in 2004 and 200539,40 also failed to demonstrate any significant benefit associated with complex stenting compared with simple stenting. The reasons for this have yet to be elucidated.
As is evident from this short review, recent advances have pushed the frontiers of interventional cardiology further into the realm of complex coronary artery lesion management, once the sole domain of the cardiothoracic surgeon. However, a number of complexities and issues remain unresolved, particularly the long-term safety of DES. With continuous advances in both materials and operator proficiency, exciting times lie ahead for the interventional cardiologist.