Background

Chronic total occlusion (CTO) remains a challenging lesion subset when considering percutaneous coronary intervention (PCI). Until recently, CTO lesions were associated with relatively low procedural success rates ranging between 60–70% despite evidence of considerable case selection1 ,2 However, the emergence of new techniques and technologies is revolutionising the field, such that procedural success rates in excess of 90% have been described by specialist operators.3 While it has long been appreciated that CTO revascularisation can improve symptoms,4 there is an increasing body of evidence to suggest prognostic benefit may follow.5

In this issue of Heart, Michael et al describe outcomes following CTO PCI among patients with previous coronary artery bypass graft surgery (CABG).6 They demonstrate that prior CABG remains a challenge in CTO PCI, with lower procedural success rates than CTO lesions in previously ungrafted patients. However, the most powerful aspect of their data is that the reporting US centres are consistently achieving high rates of procedural success (85%) despite treating increasingly complex patients. In their cohort 37% of patients had undergone prior CABG, a substantially greater proportion than any other reported registry. This suggests greater patient selection among previous registries, where CTO patients with more complex disease may have been excluded from revascularisation, a situation likely to reflect real world clinical practice. Patients who have symptoms, significant ischaemia, and/or myocardial viability may often be excluded from revascularisation on the basis of feasibility of percutaneous revascularisation —that is, anatomy rather than clinical need.

A lost population?

Although chronic occlusions may be present in up to 35% of patients undergoing coronary angiography,7 CTO PCI accounts for only around 5% of all elective PCI procedures.8 Many patients with single vessel de novo CTO are not offered revascularisation at all. Among patients with multivessel disease undergoing PCI, the presence of a CTO is a predictor of incomplete revascularisation, and in turn adverse outcome.9 In the Syntax study, incomplete revascularisation was a predictor of adverse clinical outcome at 4 years.10 Complete revascularisation was achieved in 53% of PCI patients, and 67% of CABG patients. A CTO was present in 36% and 40% of incompletely revascularised PCI and surgical patients, respectively. Meanwhile we have demonstrated that many patients who have an unsuccessful initial CTO PCI procedure are not offered repeat PCI or CABG, and have worse outcomes as a consequence.2 While these data do not answer the question of appropriateness (eg, whether an un-revascularised CTO territory is viable or ischaemic), they demonstrate that many patients with CTO are not being offered revascularisation.

Barriers to CTO revascularisation

The barriers to CTO PCI are multifactorial, but are predominantly procedure rather than patient related. The traditional view of CTO PCI has been of an inexact science, where even in the best hands success is unpredictable, and where procedure duration, contrast load, and radiation may have an adverse impact on the operator, catheter lab efficiency, and most importantly the patient. Thus a patient presenting with a significant de novo right coronary stenosis with symptoms and demonstrable ischaemia will (appropriately) undergo PCI in the vast majority of cases. A patient with an identical clinical presentation and physiology and a CTO with unfavourable clinical and angiographic features11 is more likely to be managed medically. As the anatomy is perceived to become more technically challenging the lack of prognostic benefit for revascularisation is often cited as a rationale to persist with medical therapy. However, an increasing body of registry data comparing outcomes following successful versus unsuccessful CTO recanalisation challenge this perception.1 ,2 ,5 In addition, patients presenting with acute coronary syndrome (ACS) and ST elevation in the presence of a CTO have substantially worse outcomes than those with non-CTO multivessel disease—the so called ‘double jeopardy effect’.12 Patients with prior CABG and a CTO are often not revascularised as the surgical risk may be deemed too high, especially where the internal mammary graft is intact, and where the occlusion segment may be longer and heavily calcified. Many clinicians remain unaware that contemporary CTO techniques can achieve success in this cohort. Michael et al report the largest series of such patients treated to date.6

Innovation in CTO PCI

Despite improvements in guide wire technologies, the traditional antegrade wire escalation approach to CTO recanalisation remains successful in only 70% of selected cases. In particular, longer occlusions with calcification and tortuosity are less favourable for purely wire based approaches (box 1).11 Commonly the coronary guide wire tracks into the subintimal space, with no guarantee of distal re-entry into the true vessel lumen. Two key innovations have developed and evolved to enhance procedural success: retrograde wiring via collateral channels; and manipulation of the subintimal space both retrogradely and antegradely to facilitate equipment passage.

Retrograde techniques

The retrograde technique was the first step in transforming contemporary success rates in CTO PCI. Where proximal cap anatomy is unfavourable, in particular a blunt stump with an associated side branch, wiring of the occlusion retrogradely was described as an alternative to antegrade wire techniques. Dedicated wires and microcatheters have since been developed that expedite access to the target vessel distal to the occlusion more predictably using septal and (less frequently) epicardial channels. However, wiring through the occlusion segment directly back into the proximal true lumen is achieved in the minority of retrograde cases.13 As with antegrade wiring, the retrograde wire often tracks into the subintimal space, such that re-entry into the proximal true vessel lumen can be difficult.

Dissection re-entry

The ability to understand, negotiate, and manipulate the subintimal space has been the next key step in improving success in contemporary CTO PCI, whether operating antegradely or retrogradely. As a consequence of both the resilience and distensibility of the coronary adventitia, blunt dissection techniques have been developed to negotiate safely around highly calcific, non-penetrable CTO segments that previously could not be traversed with purely guide wire based strategies.

Retrograde dissection and re-entry (RDR) is an essential component of the retrograde CTO technique. With a retrograde wire positioned within the occlusion segment (either luminal or subintimal), an antegrade system is advanced into the occlusion segment parallel to it, and balloon dilatation usually performed antegradely. This facilitates co-localisation of both antegrade and retrograde systems within the vessel architecture, whether subintimal or luminal (figure 1). A single guide wire can then be delivered through the occlusion segment, providing continuity between the true lumen proximally and distally. Angioplasty and stenting is then performed antegradely in the usual fashion, commonly over a wire that has been externalised through the antegrade guiding catheter.14 However, retrograde techniques require a suitable interventional collateral. Where collateral options are limited, and the anatomy is unfavourable for antegrade wiring, an alternative strategy is required.

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Figure 1

Techniques for chronic total occlusion (CTO) recanalisation. (A) Antegrade wiring through the CTO plaque segment (green wire), used for short occlusions (<20 mm) with a clear proximal cap. (B) Retrograde wiring through the CTO plaque segment (blue wire), used for short occlusions with proximal cap ambiguity in the presence of an interventional collateral option. (C) Antegrade dissection re-entry (ADR). Using a dedicated over-the-wire crossing technology, a guide wire (green wire) is positioned antegradely from within a controlled subintimal dissection plane into the distal true lumen. The technique is used in long occlusions with a clear proximal cap, and a favourable distal re-entry zone, without severe atheroma, or at a bifurcation. (D) Retrograde dissection re-entry (RDR). Balloon inflation over an antegrade wire positioned within the subintimal space (green wire) expands that space to facilitate passage of a retrograde guide wire (blue) from the subintimal space back into the proximal true lumen. The technique is used in long occlusions with proximal cap ambiguity and/or an unfavourable distal vessel for antegrade re-entry, in the presence of a suitable interventional collateral.

Antegrade dissection and re-entry (ADR) is conceptually identical to RDR. The difference is that the operator initially has control of the proximal lumen only. Subintimal tracking and re-entry (STAR)15 was the first reported ADR technique. It involved forceful advancement of a knuckled polymeric guide wire within the subintimal space towards the distal branches of the occluded vessel to create a communication between true and false lumens. The technique was limited, however, as there is no control over the location of the distal re-entry point, resulting in long dissections to the terminal branches and consequential occlusion of more proximal branches. However, the technique did effectively demonstrate that blunt dissection through the subintimal space could traverse occlusion segments rapidly, and without perforation of the adventitia. This stimulated the development of controlled subintimal dissection and distal vessel re-entry techniques, which minimise the size and length of the dissection plane, utilise visualisation of the distal vessel using contralateral injections, and include a dedicated crossing technology to access the lumen from the dissection plane (figure 1). The FAST (Facilitated Antegrade Steering Technique) CTO study16 demonstrated the safety and efficacy of the Bridgepoint System (Boston Scientific USA), which has become a preferred system for controlled antegrade re-entry from the subintimal space.

Uptake of novel CTO skillsets

Despite these advances there has been limited uptake to date of these techniques into routine clinical practice. A third key innovation has been the development of a mechanism to allow the operator to integrate the available techniques and technologies and understand where each may be expected to succeed.

The hybrid algorithm for CTO PCI17 was conceived with the aim of developing a systematic approach to CTO PCI that could be safe, reproducible, efficient (with respect to contrast, radiation, time, and catheter lab utilisation), and most importantly successful (figure 2). The goal was to standardise the initial and provisional procedural approaches to CTO PCI. At the centre of the algorithm are key principles. First, clinical criteria determine the decision to revascularise, while coronary anatomy dictates the interventional strategy. Secondly, multiple techniques may be utilised during a case, with the switch from a failing strategy occurring at an early stage to optimise the likelihood of success. Thirdly, where multiple interventional strategies are equally applicable, the most efficient should be employed in terms of contrast, radiation, and operating time, all of which are associated with patient outcomes.

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Figure 2

The hybrid algorithm for chronic total occlusion percutaneous coronary intervention (CTO PCI). The algorithm demonstrates provisional approaches based on anatomical features, with a switch from a failing strategy advised at an early stage. ADR, antegrade dissection re-entry; RDR, retrograde dissection re-entry. Adapted with permission from Brilakis et al.17

Utilisation of the algorithm requires detailed angiographic review and procedure planning. The interventional approach is decided by four simple angiographic features: the nature of the proximal cap, the length of the occlusion, the nature of the distal landing zone (whether diffusely diseased, at a bifurcation, and the degree to which it can be adequately visualised), and finally whether there are interventional collateral options. Dual catheter injections at the time of intervention are essential to optimise visualisation and/or utilisation of collaterals. While cases may be planned as more likely to be completed antegradely or retrogradely, all feasible strategies should be available at the time of intervention. Thus the concept of an antegrade attempt followed by referral for a future retrograde procedure if unsuccessful would be avoided, as intraprocedural failure to progress antegradely would encourage a switch to retrograde at an early stage, and vice versa. Successful application of the algorithm demands both an understanding of the anatomy, and training in the key skillsets of antegrade wiring, antegrade dissection re-entry, and retrograde CTO PCI.

Dedicated CTO programmes

The success rates of the groups reporting in Heart and similar groups in North America, Europe and the UK are the consequence of structured training and education. Attendance at didactic or live case events are a starting point, but cannot enable new operators to achieve immediate success. The skillsets described here should be applicable to any trained interventionist, but success will be best achieved by a small number of designated operators per centre to ensure sufficient case volume to develop proficiency.

Successful programmes are increasingly being developed through local training days involving groups of interventionists with an interest in CTO coming together to operate collectively with visiting trainers available for advice and hands on assistance where appropriate. Centres adopting the hybrid approach have also invited trained individuals (or proctors) to join them for more complex cases. There are similarities between this model and that of structural intervention programmes such as transcatheter aortic valve implantation (TAVI), with the important distinction that training is not based on any single device, but an integration of a number of enabling techniques and technologies. More recently additional training resources have become available with the opportunity to share clinical experience within an international CTO online community (ctofundamentals.org).

While procedural success depends on operator training, the success of a programme is contingent on clinical assessment, and case selection. CTO interventionists therefore need to communicate effectively with general cardiologists, interventionists, cardiac surgeons, and imaging colleagues, to ensure that patients with a CTO and clinical indications are appropriately investigated and referred, irrespective of the coronary anatomy. Existing multidisciplinary heart team meetings are an ideal forum, with the added opportunity to highlight the correct CTO specific diagnostic angiographic projections to trainees and colleagues alike.

Future challenges

Integrating the key CTO strategies into an understandable, reproducible, and teachable algorithm offers an opportunity to treat more complex anatomy, and therefore meet the needs of a wider patient population. However, calcification, vessel tortuosity, and adverse proximal cap anatomy remain important technical challenges—all issues frequently encountered in previous bypass surgery patients. Although contemporary CTO success rates approach 90%, Michael et al6 demonstrate that despite utilising retrograde techniques in almost half of the CABG cohort, technical success was lower than in non-CABG patients. There is therefore a need for continued innovation in CTO PCI, and in turn the interventional algorithm will evolve.