A Primer on Chronic Total Occlusion (CTO) Percutaneous Coronary Intervention for the Cath Lab

A question came from one of our cath lab staff, who asked if we could describe how chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is done and what the options are for a successful procedure. For full disclosure, I am a strong advocate of our trainees learning CTO technique, as noted in one of the earlier CLD editor’s pages (see June 2015’s Chronic Total Occlusion [CTO] Revascularization: Seeing the Future), but I am not a CTO operator, as we have elected to concentrate clinical expertise in only a couple of selected interventionalists. The four stages of learning CTO PCI (Figure 1) are described by Peter Tajti and Emmanouil S. Brilakis.¹ Case complexity and success rates increase with the operator’s skill acquisition and experience over time. Dr. Arnold Seto and I thought we could provide a primer on the techniques, indications, complications, and clinical benefits for the lab staff. The crossing strategies for CTO PCI will be summarized in a simplified form to enhance our understanding of this significant technical advance in coronary intervention. There are several good references for more in-depth understanding in the suggested readings.  

CTO Success and Outcomes (Table 1)

CTOs are found in up to 20% of patients. CTO PCI success rates in experienced centers ranges from 85-90%, significantly higher than the 50-80% reported for an all-comer registry rate. Increased CTO success comes with experience and use of novel equipment and techniques, as well as comprehensive training in high-volume CTO centers. New as well as experienced operators can increase their success through continued education, live case workshops, and proctoring. Concentrating experience in a few motivated operators is recommended for most laboratory operations.

While the benefits of CTO PCI have been thought to be positive, at this time there are few randomized, controlled trials demonstrating an unequivocal benefit of CTO revascularization. Lack of positive trial outcomes are in part related to study designs and limitations, which may include a high prevalence of non-CTO lesions that are treated without lesion-specific ischemia or symptoms, high rates of crossover from medical therapy to CTO PCI, and only mild baseline symptoms, which obscures the main benefit of CTO improvement and will not likely demonstrate improvement in mortality. The best outcomes with CTO PCI are in patients who are symptomatic or who have demonstrated ischemia or viability on stress testing, similar to typical PCI procedures.   

Complications of CTO PCI (Table 2)

The main complications of CTO PCI are perforation (1-4%), ischemia, and acute vessel closure. Other complications are those typical for non-CTO PCI and coronary angiography in general. Figure 2 diagrams the complications that may be encountered with CTO PCI.  

High radiation exposure is also of concern for CTO patients, operators, and staff. Stopping the procedure because of high radiation exposure should be strongly considered when a limit of 5 to 10 Gy air kerma dose has been reached. In such cases of high radiation exposure, post procedural monitoring and referral for dermatologist follow-up are recommended for air kerma doses >5 Gy.

CTO PCI Techniques

There are three main CTO techniques:  antegrade wire escalation (AWE), antegrade dissection and reentry (ADR), and the retrograde approach. Each method is used as appropriate for the anatomy (Figure 3). 

Antegrade Wire Escalation (AWE)

The AWE method is used for the lower complexity occlusions. While there are several variations, one method begins with a microcatheter and guidewire. Microcatheters are preferred to over-the-wire (OTW) balloons, because they are more flexible, with a lower profile. To cross the CTO, a specialized CTO guidewire is selected and the tip is shaped (NB: the Gaia guidewires [Asahi Intecc] have pre-shaped tips). In contrast to standard PCI tip bends, a small (1 mm long, 30- to 45-degree) distal bend is usually preferred. The shaped guidewire selected to cross the CTO replaces the workhorse wire. 

To cross the CTO, the guidewire is advanced using sliding, drilling, or penetration, or a combination of these techniques. Sliding is performed with the forward movement of a tapered, polymer-jacketed guidewire into microchannels within the CTO. Drilling is performed by controlled rotation of the guidewire in both directions. Penetration consists of forward guidewire advancement intentionally directing the wire in different planes. This maneuver is often best done using a stiff wire (Gaia Third or Confianza Pro 12 [Abbott Vascular]) to penetrate the cap of the occlusion. 

Forceful antegrade injections should be avoided, because hydraulic force can propagate a dissection along the guidewire. Antegrade injection may turn a benign guidewire perforation into an uncontrolled, free-flowing perforation. If an automatic injector is used, it should be limited to contralateral angiography.

There are three potential wire positions: (a) crossing into the distal true lumen, (b) passing into the subintimal space, and (c) exiting the vessel structure (wire perforation). Wire position is most commonly assessed by retrograde angiography. Inadequate wire support and penetrating force often requires specialized microcatheters such as the Corsair (Asahi Intecc) or Turnpike (Teleflex) catheters.  Upfront use of such microcatheters will tend to reduce procedure times by allowing for wire exchanges as needed to cross the lesion.

Once the wire is across the lesion, balloon angioplasty and stenting can usually proceed. Occasionally a lesion is not crossable with a balloon, requiring laser or rotational atherectomy techniques. Rotational atherectomy mandates, however, an exchange of the CTO guidewire for a Rotawire (Boston Scientific), which can be especially challenging and sometimes not possible to pass distally.

Antegrade Dissection/Reentry (ADR)

The ADR technique uses the subintimal (or subadventitial) space for crossing the occlusion, followed by reentry into the distal true lumen using guidewires or unique balloon systems, such as the Stingray balloon and guidewire (Boston Scientific). ADR technique is a key component of contemporary CTO PCI, especially for crossing more complex occlusions. Despite concerns about using the subintimal space, ADR recanalization is associated with favorable short- and long-term outcomes. 

The first ADR method described was called the subintimal tracking and reentry (STAR) technique. It involves forceful advancement of a polymeric guidewire with a curve tip (knuckled) within the subintimal space toward the distal branches of the occluded vessel to connect the false and true lumens. The reentry was often uncontrolled and unpredictable, and the knuckled guidewire could create a wide dissection plane. 

The use of the CrossBoss catheter (Boston Scientific) is designed to provide a controlled dissection of the subintimal space, followed by the Stingray LP balloon placed at the proposed reentry site. The Stingray wire is then used to puncture the intimal flap and re-enter the true lumen (Figure 4). With this method, a more controlled reentry point can be achieved.

The Stingray balloon is 2.5 mm in diameter, 10 mm in length, and has a flat shape with two side exit ports opposed 180 degrees apart; upon low-pressure (2-4 atmospheres [atm]) inflation, it orients with one exit port facing the true lumen and one exit port pointing away from the true lumen (Figure 5). This configuration allows for wire puncture into the distal true lumen when oriented toward the appropriate port. The 0.014-inch Stingray wire has an icepick-like prong at its tip to facilitate puncturing into the true lumen. Once the lumen has been punctured, the Stingray wire can be advanced after a retrograde contrast injection confirms the wire is in the true lumen, or exchanged with a workhorse wire (“stick and swap”). The Stingray balloon is then deflated and exchanged for an over-the-wire catheter to perform subsequent dilatation and stenting of the CTO.

The Retrograde Approach

The retrograde approach involves advancement of a guidewire through a collateral vessel or bypass grafts into the distal true lumen, followed by CTO crossing against the antegrade direction of blood flow. Similar to ADR, the retrograde approach is an essential tool for achieving high success rates in CTO PCI. Retrograde CTO PCI is especially useful in more complex cases and when antegrade crossing strategies are not feasible or fail. 

However, the retrograde approach carries higher risk for procedure-related complications.  The European CTO Club reported 75% technical and 71% clinical success among 1582 retrograde CTO PCIs, with significant improvement over time. The overall procedural complication rate was 7%, whereas the in-hospital major adverse cardiac and cerebrovascular event rate was 0.8%. During a mean follow-up of 25 months, all-cause mortality rate was 4%, cardiac mortality rate was 2%, and the overall major adverse cardiac and cerebrovascular event rate was 13%.

Using a retrograde approach, a CTO wire can be passed lumen-to-lumen, which occurs in the minority of cases (10-20%) or by dissection-reentry as in most other cases (Figure 6). The definition of a satisfactory “interventional” collateral channel varies among operators and depends in large part on the operator’s experience. There are two primary types of retrograde conduits: collateral channels or surgical bypass grafts and are the preferred pathways for retrograde crossing, because they are easier to cross and carry a lower risk for complications. The following steps are used in many retrograde CTO PCIs: 

Step 1: Getting to the collateral channels. 

Step 2: Crossing a collateral channel. 

Step 3: Advancing the microcatheter to the distal CTO cap. 

Step 4: Crossing the CTO.

Step 5: Externalization of the retrograde guidewire, or dissection reentry towards the antegrade guidewire.

Step 6: Antegrade PCI on an externalized guidewire or antegrade guidewire. 

Step 7: Pulling out the retrograde gear.

The Hybrid CTO Algorithm

The hybrid approach (Figure 7) starts with dual angiography and focuses on assessment of four anatomic features (proximal cap ambiguity, distal target vessel, suitable interventional collaterals, and lesion length) to determine the initial crossing strategy. Setting up for all potential strategies (including retrograde techniques) increases the change of a successful outcome and reduces the need for repeat procedures. It is recommended that an early (every 5-15 minutes) change in approach occur if the initially selected strategy is not successful.

CTO Operational Considerations 

For femoral approaches, 8 French (Fr) guiding catheters are preferred, because they provide the strongest support and the ability to use balloon trapping and balloon anchoring techniques. Access with ultrasound and fluoroscopic guidance will reduce the risk for access complications. Most operators prefer bilateral femoral access with 8 Fr catheters to accommodate special equipment. Long (45 cm) 8 Fr sheaths also enhance catheter support and are frequently used. Radial access may be limited to smaller guide catheter diameters and equipment options. The most commonly used guide types are Amplatz left (AL) 1 for the right coronary artery (RCA) and a supportive C-curved catheter (e.g., XB 3.5 or EBU 3.75) for the left coronary artery. Side hole guides may allow some antegrade flow, but may provide a false sense of security with deep intubation, because flow through the side holes is simply inadequate. Guide catheter extensions (GuideLiner [6-8 Fr] [Teleflex], Guidezilla [6 Fr] [Boston Scientific]) and side-branch anchoring may be needed during CTO PCI.

Ad Hoc vs Planned Approach

CTO PCI should be planned as a stand-alone procedure rather than ad hoc following a diagnostic procedure. This approach will allow for reduced contrast load and radiation dose. The lab staff can ensure that adequate cath lab time is available, necessary equipment is secured, and a ‘game plan’ is in place. The plan is based on the angiography review, assessment of technical strategies, and discussion with the patient and his or her family regarding the risks and benefits of the procedure. Some cases may benefit from a heart team approach. Because the CTO procedure can be prolonged, many labs adopt a dedicated CTO day. Adequate lab time and flexibility for those procedures that take longer to complete than expected will ease the stress in the lab.

The Bottom Line for CTO PCI 

• Have a “game plan” and set contrast, radiation, and table time limits. A game plan for approaching the CTO begins with a detailed review of the diagnostic coronary angiogram.   
• Use bilateral coronary angiography to characterize CTO length and course. 
• Anticoagulation: Unfractionated heparin is preferred because it can be reversed if a complication occurs. Glycoprotein IIb/IIIa inhibitors or bivalirudin should be used sparingly, it at all.  
• Contrast/radiation limits: The amount of contrast considered acceptable relates specifically to the risk of contrast-induced nephropathy. Radiation doses should be monitored and relative limits determined before the procedure is started.
• Use a stepwise strategy for CTO recanalization, moving expeditiously from one technique to another based on the algorithm in use.
• Be aware of stopping points, particularly in regard to perforations. Stop if a type II or III perforation occurs and manage with anticoagulation reversal, balloon tamponade, and covered stent techniques if necessary. 

Suggested Reading

1. Brilakis ES, Tajti P. Chronic total occlusion percutaneous coronary intervention: evidence and controversies. J Am Heart Assoc. 2018;7:e006732 
2. Tajti P, Burke MN, Karmpaliotis D, et al. Update in the percutaneous management of coronary chronic total occlusions. JACC Cardiovasc Interv. 2018 Apr 9; 11(7): 615-625.
3. Michael TT, Papayannis AC, Banerjee S, Brilakis ES. Subintimal dissection/reentry strategies in coronary chronic total occlusion interventions. Circ Cardiovasc Interv. 2012; 5: 729-738.

Disclosure: Dr. Kern is a consultant for Abiomed, Merit Medical, Abbott Vascular, Philips Volcano, ACIST Medical, Opsens Inc., and Heartflow Inc.