High Success, Low Complications for Chronic Total Occlusion Revascularization in the Cath Lab: The EXPERT CTO Trial

Can you define a chronic total occlusion (CTO)?

CTOs are a high-grade native coronary stenosis with TIMI grade 0 or 1 flow, typically of at least three months’ duration. 

The three-month duration is generally a best clinical estimate, based on changes in EKGs, patients having an antecedent angiogram, or a prior stress test. CTOs occur in all of the coronary arteries and their prevalence is anywhere from 15-20% of all individuals who undergo diagnostic cardiac catheterization, and the prevalence may be even higher among individuals with multi-vessel coronary disease. 

There has been, for several decades now, a great deal of attention devoted to the pathophysiology of chronic total occlusions. It should be stated, too, that CTOs occur in any part of the arterial vasculature. They commonly occur in the legs and in other arteries besides the heart. There has been a great deal of attention to coronary CTO pathophysiology over the years. Generally, coronary CTOs can be a mix of different components; namely, calcium, soft atherosclerotic plaque and dense fibrous tissue, as well as organized thrombus. So coronary CTOs can really represent all four features in various different degrees of prevalence. CTOs are some of the most commonly identified lesion subsets, and yet they are often the least frequently treated. 

Is there a timeframe for CTO development?

CTOs can occur acutely and go unrecognized, as silent clinical events, but probably in more instances than not, they occur gradually over time. Often the area of the myocardium that is subtended by the totally occluded vessel is still very viable and functional despite having an occluded artery, because over time, collaterals have developed to keep the heart tissue alive. However, the collaterals have not been shown to supply enough blood and oxygen required when the demand of the heart muscle increases. 

What do we know about collaterals?

You can see collaterals by computed tomography angiography (CTA), micro CT, and commonly, in the cath lab, under diagnostic angiography alone. Collateral channels are graded by a visual score based on the angiogram. Put simply, collaterals can emanate from the same vessel, what we call ipsilateral collaterals, that on the more proximal segment will then bridge past the occlusion and supply the downstream vessel. Or, collaterals can occur from contralateral arteries; for example, a right coronary artery chronic total occlusion may derive collaterals through the septum of the left ventricle from the left anterior descending artery. Many times these collaterals are visible on angiography alone, but there are also many microchannel collaterals that are not routinely visible. For interventional cardiologists considering a retrograde strategy for CTO recanalization, collaterals are typically characterized as septal or epicardial in location, and their anatomic course and size are important determinants of procedural outcome.

Why are some interventionalists reluctant to treat CTOs in the cath lab?

The presence of a CTO has long been recognized as the primary reason for referral to bypass surgery. It is also the most common reason for relegation of patients with significant coronary disease to medical treatment alone. What we have observed in cardiovascular medicine is what I would term a “treatment paradox” both for bypass surgery and for percutaneous revascularization. Specifically, as disease burden and complexity increase, ironically, both among surgeons and as interventional cardiologists, we perform less revascularization. This reluctance to act is largely based on historical misperceptions around the relevance and clinical impact of CTO revascularization. There are misunderstandings regarding the appropriateness and need to treat CTOs, and a lack of awareness of the benefits of treating CTOs as well. There has been a limited understanding of patients who would truly benefit from the procedure relative to perceptions around procedural failure and risk. In many instances, what clinicians do is treat the angiogram — in other words, they make decisions based on angiographic appearance, rather than on treating the patient’s need for an open artery to improve angina, heart failure or other indications. For example, let’s say a physician has a patient with a CTO of the right coronary artery, and another, similar patient, with the same symptoms, who has a 75% narrowing of the right coronary artery. Well, that physician might be very quick to place a stent in the right coronary artery of the patient with significant but non-occlusive disease and with symptoms, but is more likely to choose not to treat the CTO patient with revascularization. 

How has CTO treatment developed over the past few years?

CTO percutaneous coronary intervention (PCI) has changed substantially over the past five to seven years. For example, patient identification for appropriateness is not only based on symptoms and standard imaging such as a stress test, but also CT angiography, which helps delineate the anatomy of the occluded vessel. MRI imaging can also identify viability in the areas of the chronically occluded vessel. The goal is to determine appropriateness and identify those patients who would receive the greatest benefit from the procedure. In addition, more literature has been published as of late to dispel some of the myths of CTO revascularization; in particular, to demonstrate that CTO PCI can be associated not only with a significant reduction in angina burden and improvement in quality of life, but that it also can reduce the potential for arrhythmias, it may improve left ventricular function, and there is even some evidence that it could reduce mortality.^1,2 The technique itself has changed as well. In the United States, I think interventional cardiologists have often felt removed from CTO revascularization³, with the impression that these very complicated procedures might be performed successfully at dedicated centers or with very expert, experienced operators, but somehow, it wasn’t translational to their own cath labs. I think we now realize that is not the case⁴, and the EXPERT CTO trial is a good example of how that has changed. Finally, the technology itself has changed. In particular, advancements in guide wires and refinements in support catheters and balloon catheters, along with more specialized catheters for reentry techniques into the true lumen, have all incrementally led to higher procedural success.

How long does a CTO procedure typically take?

CTO procedures typically require greater resource time and utilization, because of the greater complexity of having to cross the lesion first with a guide wire. The most common reason for failure of a CTO revascularization is an inability for the guide wire to successfully cross into the distal true lumen. The average total procedure time is typically about 2-2.5 hours. The number of guide wires, balloon angioplasty catheters, and stents that we use is typically greater than what we commonly use for a non-CTO PCI procedure. That being said, however, we have also demonstrated that the economic benefit of doing CTO procedures is nevertheless similar to that of performing non-CTO PCI. It has been previously suggested that CTO PCI was an economic deterrent, because of greater resource utilization, but we have recently published data showing that these procedures result in a contribution margin to the hospital that is similar to that of non-CTO PCI.⁵

Can you tell us about the hybrid technique for CTO treatment? 

The hybrid technique is an advance in our approach to treating CTOs.⁶ It is a method that permits the interventionalist to treat the patient, not just address the angiogram. Using contralateral angiography in nearly all case, the operator can move between an antegrade approach, retrograde approach, and targeted subintimal reentry approach in a dynamic fashion, so that the procedure does not stall or get stuck at one point. It permits the operator to treat the whole range of CTOs that otherwise might be limited by treatment exclusive to just an antegrade procedure or a retrograde-only procedure. Operators can use all of the available skill sets to move back and forth during the procedure in order to gain greater success. The hybrid method asks four questions: 

1. What is the lesion length?
2. Is the proximal cap of the total occlusion visible? 
3. Is there a suitable distal target or landing zone of the artery for targeted reentry into the true lumen? 
4. Are there interventional collaterals that can permit guide wires and other catheters to pass through these collaterals and open the artery from a retrograde path? 

To date, the available evidence with the hybrid approach suggests not only very high rates of procedural success beyond what we have routinely observed in large observational studies, but also suggests a high degree of safety and success across CTOs of varied complexity. Even though the artery is 100% blocked, there are some CTOs that have features that might be considered more difficult than others, such as long lesions, angulated or calcified lesions and CTOs with poorly identified proximal or distal segments. 

Can you tell us about the EXPERT CTO trial?

Despite the advances in CTO revascularization in the United States, there were still many outstanding issues that were unaddressed. In particular, we wanted to learn more about the success rates of contemporary chronic total occlusion PCI in the United States and the safety of this procedure. Second, since drug-eluting stents have remarkably reduced restenosis rates in less complex disease, we wanted to know more about the outcomes in patients with very complex disease who are treated with drug-eluting stents. A third issue was that there were very few devices that were FDA-approved for use in the treatment of CTOs. The EXPERT CTO trial represented a large opportunity for us to address these issues, and so, with the sponsorship of Abbott, we undertook a multi-center trial of 250 patients that underwent elective CTO revascularization at U.S. centers that possessed varied levels of experience in CTO PCI. Patients were treated using the Progress and Pilot wires, Mini-Trek balloons, and Xience drug-eluting stents (Abbott Vascular). EXPERT CTO is specifically designed to demonstrate the procedural safety and efficacy of these guide wires and balloons, and the long-term clinical efficacy of the Xience stent in maintaining patency in the treated arteries. Enrollment was completed in February 2013, and in fact, the sub-studies related to the guide wires and balloons have already led to their FDA approval as a formal indication for CTO revascularization. The primary endpoint related to the stent is at one year of follow-up, so we won’t have the final outcome related to the primary endpoint of the trial until about March 2014. 

What did you learn about rates of procedural success?

There are many factors that influence procedural success for CTOs. Probably no single determinant alone influences success or failure, but for the reasons previously stated, I would say the most important is operator skill set. But certainly, the available device technologies, as well as certain anatomic factors related to the CTO, such as lesion length, morphology of the CTO, and interventional collaterals, are also important determinants. Because of the variability of these aspects, the success rates vary quite broadly, and in contemporary trials, they range anywhere from 50% among unselected sites to more than 90% with dedicated operators in single centers. 

The specific results from EXPERT CTO related to guide wire and low-profile angioplasty balloon success are to be presented at the SCAI meeting in early May. In general, we report an overall success rate that approaches 90% in a multicenter experience, with operators of varied backgrounds in regard to CTO PCI. This is a procedural success rate that is substantially higher than what we have observed in previous multicenter studies. I believe it highlights the evolution in technique and treatment strategy that has occurred with more contemporary CTO PCI. Also, the success rate is accompanied by a safety margin, including peri procedural adverse events and complications, that is similar to that of non-CTO PCI. The success rates of CTO PCI are now the highest we have ever observed, with the lowest rates of complications. 

EXPERT CTO is important for clinicians, because not only does it characterize the safety and efficacy of the CTO procedure and of the use of these devices, and provide reassurance about the benefits of CTO PCI, but it also provides a large opportunity for education around CTO revascularization.

What are some of the qualities of the guide wires and other devices being used that make them uniquely suited for CTO revascularization?

Guide wires specific to CTOs may be constructed with greater stiffness at the tip for penetrating force. They may have a hydrophilic or very lubricious coating to traverse through the occluded segment, and they may also have a tapered tip to engage in microchannels within the occluded segment. Normal guide wires are typically .014” in diameter, but a specialized CTO wire might have a tip that tapers down to .009” in diameter, enabling it to engage in the small microchannels and navigate through to the distal true lumen. So the primary features of the guide wires include changes in differential tip stiffness, occasionally hydrophilic coating, and the tapered tip for microchannel engagement. The Mini-Trek balloon catheter, one of the catheters tested in this trial, is very low profile, 1.2mm in diameter. After a guide wire has successfully crossed the lesion, the low profile enables the balloon catheter to advance through the very fibrous, calcified total occlusion and permit pre-dilatation. Another catheter technology that we did not test in this trial per se (although it was used in some cases) is the CrossBoss and Stingray catheter system from BridgePoint Medical/Boston Scientific. It actually enables the guide wire to re-enter from the subintimal space where the wire may be trapped in the dissection plane, and penetrate into the true lumen of the distal vessel. 

How is CTO revascularization approached at your facility?

At Piedmont Hospital, we do >250 CTO cases per year. The case begins with determining patient appropriateness and selection. We ask ourselves, is the patient symptomatic, and how? Does the patient have an abnormal stress test? Does the patient have heart failure symptoms? Does the patient have angina symptoms? Is the patient already on appropriate medical therapy and/or has the patient failed medical therapy? We review the risks and benefits of the procedure with the patient as well, because there may be some risks specific to an individual patient. We also review the angiogram, and we look at the angiogram to answer the four questions I listed earlier in our discussion of the hybrid technique to help determine the strategy for the procedure itself. The patient comes to the hospital on a given day, and we will approach the procedure based on the anatomy. It may be a purely antegrade approach with a guide wire, it may be a retrograde approach where we pass through collaterals and cross the vessel from a retrograde fashion, or it may be some type of hybrid approach as well, where we use both techniques to open the artery. No case is ever alike. Our patients typically stay overnight and go home the following day. n

Dr. Kandzari can be contacted at: david.kandzari@piedmont.org.

Disclosure: Dr. Kandzari reports research/grant support from Abbott Vascular, Medtronic CardioVascular and Boston Scientific; and consulting honoraria from Medtronic and Boston Scientific.

References

1. Stone GW, Kandzari DE, Mehran R, Colombo A, Schwartz R, Bailey S, et al. Percutaneous recanalization of chronically occluded coronary arteries: a consensus document: Part I. Circulation. 2005; 112: 2364-2372.
2. Stone GW, Reifart NJ, Moussa I, Hoye A, Cox DA, Colombo A, et al. Percutaneous recanalization of chronically occluded coronary arteries: a consensus document: Part II. Circulation. 2005; 112: 2530-2537.
3. Kandzari DE. Import and export of interventional technique: something to declare at the border. J Am Coll Cardiol Intv. 2009; 2: 843-845.
4. Karmpaliotis D, Michael T, Brilakis ES, Lembo NJ, Kalynych A, Carlson H, Banerjee S, Lombardi W, Kandzari DE. Retrograde coronary chronic total occlusion revascularization: procedural and in-hospital procedural outcomes from a multicenter registry in the United States. J Am Coll Cardiol Intv. 2012;5:1273-1279.
5. Karmpaliotis D, Lembo N, Kalynych A, Carlson H, Lombardi WL, Anderson CN, Rinehart S, Kirkland B, Shemwell KC, Kandzari DE. Development of a high-volume, multiple-operator program for percutaneous chronic total coronary occlusion revascularization: procedural, clinical, and cost-utilization outcomes. Catheter Cardiovasc Interv. 2013 Apr 11. doi: 10.1002/ccd.24387
6. Brilakis ES, Grantham JA, Rinfret S, Wyman RM, Burke NM, Karmpaliotis D, Lembo N, Pershad A, Kandzari DE, Buller CE, DeMartini T, Lombardi WL, Thompson CA. A percutaneous treatment algorithm for crossing coronary chronic total occlusions. J Am Coll Cardiol Intv. 2012; 5: 367-379.

June 15: CTO Regional Training Course

Join co-chairs David E. Kandzari, MD, PhD, FSCAI, and William L. Lombardi, MD, FSCAI, on June 15th for the one-day Chronic Total Occlusion (CTO) Regional Training Course in Atlanta, Georgia. More information is available at https://www.scai.org/CTOAtlanta.