Coronary chronic total occlusions (CTOs) are lesions with thrombolysis in myocardial infarction (TIMI) 0 flow for ≥3 months¹ and are commonly found in patients undergoing coronary angiography (in 18.4% to 52%).^2-5 Patients with coronary CTOs are often referred for coronary artery bypass graft surgery (CABG),^2,3 but percutaneous coronary intervention (PCI) is the preferred mode of revascularization for several patients, especially those with prior CABG and those with isolated right coronary artery CTO.⁶

Although no randomized controlled clinical trials comparing CTO PCI with medical therapy have been published to date, there is a growing body of evidence suggesting clinical benefits of CTO PCI. These benefits include an improvement in anginal symptoms,^7,8 decreased anti-anginal medication intake, improved exercise capacity,⁹ improved left ventricular systolic function,¹⁰ decreased risk for arrhythmias,¹¹ and improved survival among patients with successful versus failed CTO PCI.¹² Moreover, CTOs are the most common reason for failing to achieve complete revascularization,¹³ and incomplete revascularization is associated with worse clinical outcomes as compared with complete revascularization.^14,15

Traditionally, CTO PCI has been considered a highly challenging procedure with low success rates. In a recent analysis from the American College of Cardiology (ACC) National Cardiovascular Data Registry (NCDR) CathPCI Registry, CTO PCI represented only 3.8% of the total PCI volume for stable coronary artery disease and was associated with lower procedural success (59% vs. 96%, p <0.001) and higher major adverse cardiac event rates (1.6% vs. 0.8%, p <0.001) than non-CTO PCI.¹⁶ However, higher operator annual CTO PCI volume was associated with improved success without a significant increase in major complications. The major reason for CTO PCI failure is inability to cross the lesion with a guidewire.¹⁷ Many experienced centers have reported that contemporary crossing techniques and devices have significantly improved the likelihood of CTO PCI success.^18-20

CTO PCI starts with a careful review of the coronary angiogram that, in nearly all cases, should be performed using dual injection (Figure 1).²¹ Procedural plans are then made based on the lesion angiographic characteristics, while maintaining flexibility in case the initially selected crossing approach fails to achieve progress.²¹ The three major CTO crossing techniques currently being used are: 1) antegrade wire escalation, 2) antegrade dissection/re-entry and 3) retrograde. A brief overview of the basics and recent developments of each approach follows.

Figure 1: "Hybrid" Algorithm for Crossing CTOs

Antegrade Wire Escalation

Antegrade wire escalation is the most commonly used CTO crossing approach.^1,22 A microcatheter is advanced to the proximal cap of the occlusion, followed by crossing attempts using various guidewires. Currently, the most common initial guidewire choice is a soft tip, polymer-jacketed tapered guidewire (such as the Fielder XT, Asahi Intecc). If this fails to cross, then either a stiff, polymer-jacketed wire (such as the Pilot 200, Abbott Vascular; Santa Clara, California) or a stiff, tapered wire (such as the Confianza Pro 12, Asahi Intecc) are used.²¹ The recent introduction of composite core stiff guidewires (Gaia first, second, and third, Asahi Intecc) could further improve antegrade wiring success due to good torque control, but also require different manipulation (slower manipulation to allow torque transmission from the proximal to the distal end of the guidewire).

Understanding the course of the guidewire is critical both for enhancing the likelihood of success and for minimizing the risk for complications. This can be accomplished in most cases using dual coronary injection. If the guidewire enters the distal true lumen (as confirmed in two orthogonal projections), the microcatheter is advanced past the occlusion, and the guidewire is exchanged for a workhorse guidewire, followed by balloon angioplasty and stenting.

If the guidewire exits the vessel, it is withdrawn and redirected. If the guidewire crosses the occlusion but enters the subintimal space, true lumen re-entry could be achieved using a "parallel wire" technique or (more commonly in North America) using a dedicated re-entry system (Stingray balloon and guidewire, Boston Scientific).

Antegrade Dissection/Re-Entry

Dissection/re-entry refers to the intentional use of the subintimal space for crossing coronary CTOs. This technique was introduced by Antonio Colombo, MD, FACC, who originally advanced a knuckled guidewire through the subintimal space until it spontaneously re-entered into the distal true lumen (subintimal tracking and re-entry [STAR] technique).²³ Various modifications of this technique have been subsequently developed, but a challenge with all extensive dissection/re-entry strategies is the high rate of restenosis and reocclusion that accompanies them.²⁴ As a result, these techniques are currently used only as a last resort if all other approaches fail.

Limited dissection/re-entry strategies appear to have better short- and long-term outcomes.^25,26 Dissection can be achieved with the CrossBoss catheter (Boston Scientific; Natick, Massachusetts), which is a stiff, metallic, over-the-wire catheter with a 1 mm, blunt, rounded, hydrophilic-coated, distal tip that can advance through the occlusion when the catheter is rotated rapidly using a proximal torque device ("fast spin" technique).^1,27 In approximately one in three cases, the catheter enters the distal true lumen, whereas in the remaining two thirds, it creates a limited dissection plane that facilitates true lumen re-entry.

Re-entry can be achieved using the Stingray system (Boston Scientific).^28-30 The Stingray balloon is a flat 1 mm balloon with three exit ports that communicate with a common lumen. The distal port is used to advance the balloon into position. The other two ports, one proximal and one distal, are 180° opposed. When the balloon is inflated, it self-orients so that one port is facing the true lumen and the other is facing the adventitia. The Stingray guidewire is a stiff, angled guidewire with a 0.0035 inch distal taper that is advanced through the port facing the true lumen. To facilitate re-entry, the Stingray wire is often exchanged for a more steerable guidewire (such as the Pilot 200, Abbott Vascular) after re-entering the distal true lumen ("stick and swap" technique).¹

The Retrograde Approach

The retrograde approach to CTO crossing can significantly increase success rates, particularly in challenging lesions. A guidewire is advanced into the artery distal to the occlusion through either a bypass graft or collateral channels, followed by CTO crossing against the original direction of blood flow.^31,32 Retrograde crossing is usually easier because the distal cap is softer, more frequently tapered,³³ and less ambiguous¹ than the proximal cap. Bypass grafts³⁴ and septal collaterals^35,36 are preferred over epicardial collaterals because they are easier to cross and carry a lower risk of tamponade in case of rupture.

Crossing the collateral is facilitated via the use of dedicated microcatheters (such as the Corsair, Asahi Intecc, and Turnpike, Vascular Solutions) and guidewires, such as the composite core Sion guidewire (Asahi Intecc), and the soft polymer-jacketed guidewires (such as the Fielder FC, Asahi Intecc), and the Pilot 50 (Abbott Vascular). After guidewire crossing into the distal true lumen is confirmed, the microcatheter is advanced to the distal cap, followed by CTO crossing, which is usually done using a wire escalation or dissection re-entry technique.³¹ Currently, the most commonly used retrograde crossing technique is the reverse controlled antegrade and retrograde subintimal tracking (reverse CART) technique^31,32,36,37 in which an appropriately-sized balloon is advanced over the antegrade wire and is inflated in the subintimal space to enlarge it, followed by advancement of the retrograde guidewire into the space created by the antegrade balloon.³⁸ The retrograde guidewire and microcatheter are then advanced into the antegrade guide catheter followed by wire externalization, which has been greatly facilitated by the recent introduction of the RG3 wire (Asahi Intecc). Externalization provides excellent support for equipment delivery, but can also lead to complications due to deep guide catheter intubation. Therefore, disengagement of the donor vessel guide is recommended during the rest of the procedure.¹

Putting It All Together: The Hybrid Approach for CTO Crossing

The selection of initial and subsequent CTO crossing strategies depends on the angiographic characteristics of the lesion, as well as the operator's experience and level of expertise. The hybrid algorithm for CTO crossing provides a simple, yet comprehensive, approach and is commonly used in North America (Figure 1).²¹

The first step in the hybrid algorithm is dual coronary injection, which allows the assessment of four key angiographic characteristics: 1) proximal cap ambiguity, 2) quality of the vessel distal to the occlusion, 3) lesion length, and 4) presence of adequate collateral vessels (allowing adequate crossing strategy selection). Starting with antegrade wire escalation is the favored approach for <20 mm long lesions, whereas antegrade dissection and re-entry is the favored approach for ≥20 mm long lesions. A primary retrograde approach is favored for aorto-ostial occlusions, lesions with an ambiguous proximal cap, diffuse distal disease, and bifurcation at the distal cap when appropriate collateral vessels are present. Importantly, if the initially selected strategy fails to achieve satisfactory progress, early change is recommended to maximize the likelihood of success and minimize use of fluoroscopy and contrast. There is increasing evidence demonstrating that application of the hybrid algorithm is both safe and effective,^18,39,40 even among challenging patient and lesion subgroups.^41-43

How to Become a CTO Operator

CTO PCI requires a distinct skillset that is frequently contrary to what is needed during standard PCI. Although many early CTO operators were self-taught, there are currently many resources to facilitate training, such as print and online textbooks,¹ websites (such as www.ctofundamentals.org), and CTO-specific meetings (such as the annual Cardiovascular Research Foundation CTO Summit in New York City, the EuroCTO and Japan CTO Club meetings, and the Society for Cardiovascular Angiography and Interventions regional CTO meetings). The final (and often most important step) is proctorship, which is critical for successfully and safely developing the necessary skills for the procedure.

CTO PCI is best performed by high-volume operators with significant experience in CTO PCI. A EuroCTO Club consensus document suggested that "retrograde techniques should be reserved for very experienced antegrade operators (>300 CTOs and >50 per year),"⁴⁴ although a specific threshold is hard to define. Development of regional CTO centers of excellence will enhance the success and decrease the risk of the procedure.¹⁶

Conclusions

In summary, CTO PCI has undergone dramatic evolution in recent years. Excellent results can be achieved, with high success and low complication rates, among experienced centers and operators using all available techniques. Expanding the number of centers and operators that can achieve these outcomes will improve patient access to this procedure and improve clinical outcomes for an often challenging to treat group of patients.

References

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Keywords: Adventitia, Algorithms, Angina, Stable, Angioplasty, Balloon, Coronary, Arrhythmias, Cardiac, Consensus, Coronary Angiography, Coronary Artery Bypass, Coronary Artery Disease, Fluoroscopy, Intubation, Myocardial Infarction, Percutaneous Coronary Intervention, Polymers, Registries, Stents, Torque

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