Chronic Total Occlusions

General description of procedure, equipment, technique

A chronic total occlusion (CTO) is defined as the complete obstruction of a coronary artery, exhibiting TIMI 0 or TIMI 1 flow, with an occlusion duration of >3 months. The prevalence has been described as high as 30%, and 13% of cases exhibit more than one CTO.

These are a fairly challenging lesion subsets, and as such, have been neglected as targets for revascularization. CTO cases have been plagued with difficulties including inability to cross the lesion and deliver stents, increased use of resources, and up to 2 times the procedure and fluoroscopy time compared with non-CTO percutaneous coronary intervention (PCI).

Increased failure rates, technical complexity, cost (of equipment, manpower) and procedure length have historically discouraged percutaneous revascularization attempts. Compared with non-CTO PCI, the success rate of CTO PCI has been quoted as low as 50% versus 97%, where success is defined as TIMI 3 flow. It is important to note, however, that the periprocedural complication rate is similar to non-CTO cases.

With the emergence of novel techniques and advanced equipment, technical difficulties have become much less limiting. Operators trained in the CTO treatment algorithm with the mentorship of an expert can become successful using these advanced strategies. Contemporary appropriateness criteria, coupled with safety guidelines, have commenced a new era of percutaneous intervention, targeting a well-defined subset with groundbreaking ideas and technology.

Indications and patient selection

Between 2004 and 2008, the success rate for percutaneous revascularization of CTOs remained stagnant, estimated at 70%. The major adverse cardiac event (MACE) rate was low, but the PCI attempt rate was also low. This was due to the complexity of the cases, but also the notion that the territory supplied by the occluded artery was well collateralized and not significantly ischemic. A landmark study, using fractional flow reserve (FFR) to evaluate collateral blood flow, disproved this theory by revealing that collaterals are rarely sufficient to substantially reduce ischemia in CTOs.

Patients with CTOs are generally referred for angiography for refractory angina or a significant ischemic burden on noninvasive stress testing. These are the same indications for angiography in patients referred for non-CTO PCI. Historically, due to lesion complexity, the patients with CTOs were turned away. Now, given the routine success of the procedure, the indications for treatment have been more completely outlined.

Marked improvement in quality of life and symptoms, including angina, heart failure, and fatigue, have been clearly documented. CTO patients undergoing successful PCI had a significant reduction in recurrent angina compared with those who underwent unsuccessful PCI.

Cardiac mortality is in part a function of the myocardium at ischemic risk in patients treated with medical therapy. In a Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial subset, rates of death were directly related to percentage of ischemic myocardium, with myocardium at risk measured by nuclear single-photon emission computed tomography (SPECT) imaging.

Patients who derive the greatest benefit from revascularization are those with the largest burden of ischemia, even in the absence of symptoms. In an ischemia-based algorithm, measured by SPECT imaging, patients with >12.5% ischemic myocardium per summed stress score (SSS) should be considered for PCI. If the percentage is 6.25% to 12.5%, patients should be considered for PCI if they have failed maximal medical therapy.

Left ventricular function, be it regional or global, can be significantly improved as demonstrated by cardiac MRI measurements of left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and fractional shortening at 5 months postprocedure.

In terms of morbidity, patients undergoing revascularization of CTO show improved tolerance to subsequent acute myocardial infarction (AMI), most likely due to complete revascularization. The biggest predictor of mortality for a post-STEMI (ST segment elevation myocardial infarction) patient is having a CTO on medical therapy.

The presence of a CTO in a patient with multivessel disease signals a poorer prognosis and decreased survival. A recent meta-analysis of 13 observational studies revealed a 44% relative reduction in mortality in patients with successful PCI for CTO compared with their counterparts.

Medical therapy of these lesions comes with a higher 1- and 5-year mortality compared with revascularization with PCI or surgery. Unfortunately, at the time of coronary artery bypass graft (CABG), >30% of CTOs are not bypassed due to a multitude of reasons, including small size, inability to find a distal target, and diffuse disease.

Contraindications

The contraindications are the same as for non-CTO PCI. Additionally, asymptomatic patients with good exercise tolerance are generally not candidates for CTO intervention, at least based on present data.

Details of how the procedure is performed

Basics

Dual arterial access should be obtained. The placement of long femoral sheaths improves passive guide support and minimizes iliac tortuosity. Femoral-femoral guides are common and allow for larger catheters and more access for equipment.

Femoral-radial access may be used by experienced operators but size does become a limitation in some cases. The retrograde catheter should be a 90 cm guide to allow room for wire externalization if required.

This length of guide may be purchased from the manufacturer or created in the lab using a dilator as the linchpin once the appropriate length of guide has been cut from the body of the catheter. Managing guides is important, especially when a long wire has been externalized causing damping and increasing the risk for dissection. Side holes may be used for this reason; they are used more commonly in the right coronary artery, less commonly in the left coronary system.

Retrograde Approach

Anterograde success if used as the sole strategy ranges from 50% to 70%; with the addition of retrograde techniques, the success rate can improve to 90%. In experienced hands, the retrograde approach can improve success rates, lower procedural time, and decrease contrast utilization.

Based on anatomy, this approach can be used as a bailout strategy after failing antegrade, or as the primary approach based on distal cap ambiguity. Predictors of antegrade failure include long lesions, a small distal target, a side branch that is flush with the proximal cap or a bifurcation at the distal cap.

Predictors of retrograde success include a visible collateral, less than 90% tortuosity of the collateral, and less than a 90-degree angle at the anastomosis between the collateral and the CTO vessel. An operator should perform at least 100 antegrade cases before attempting retrograde maneuvers. Septal collaterals should be used by inexperienced operators before attempting the use of epicardial collaterals because of the higher risk of complications with the latter, including perforation.

A primary retrograde approach involves advancing of the retrograde wire from distal to the CTO to the proximal true lumen. Wire escalation may be used for this technique if the workhorse wire does not cross the CTO.

Exchanges for advanced CTO wires are best completed through microcatheters or over-the-wire balloons. Once in the true lumen, the wire can be advanced into the aorta and snared, or into the retrograde catheter and trapped.

Dilating the septal collateral (this cannot be done if using an epicardial collateral) with a 1.5 mm balloon may allow easier passage of equipment. Once the wire has been externalized, with or without the addition of retrograde PTCA, typical anterograde PCI may be performed.

Equipment

See Table I. Types of Wires

Table I.

Characteristic	Force	Tip	Use	Examples
Hydrophilic and/or polymer-jacketed	Low-gram	Tapered 0.009- inch tip	Antegrade probing and knuckle techniques	FielderXT™ wire (Asahi Intecc) and the Runthrough taper™ wire (Terumo).
Hydrophilic, polymer-jacketed	Low-gram	Nontapered	Collateral channel crossing(Retrograde procedures)	FielderFC™ wire (Asahi Intecc) and Pilot 50™ wire (Abbott Vascular).
Polymer-jacketed	Moderately high-gram (4-6 gram)	Nontapered	Complex lesion crossing, long lesions, knuckle technique, and dissection/reentry	Pilot 200™ wire (Abbott Vascular).
Non-jacketed tip	High-gram	Tapered	Penetration techniques: cap puncture, complex lesion crossing, and lumen reentry	Confianza Pro 12 ™ wire (Asahi Intecc)

Microcatheters

The Corsair™ microcatheter (Asahi Intecc) is a 2.7 Fr catheter with a lubricious outer coating, which provides a platform for retrograde crossing as well as support for antegrade wiring. The Finecross™ (Terumo Corp.) and Quick-Cross™ (Spectranetics Corp., Colorado Springs, CO) catheters are useful for wire support and exchange.

Small over-the-wire (OTW) balloons may also be used for wire support and exchange. The Tornus™ microcatheter (Asahi Intecc) has a braided wire mesh over the wire microcatheter with left-handed thread allowing for channel preparation and lesion crossing in resistant occlusions.

Lesion Crossing and Lumen Reentry Technologies

The Crossboss™ catheter (BridgePoint Medical) is a metal over-the-wire microcatheter with a rounded tip to prevent vessel exit. When rotated rapidly, in either direction, it can advance forward through a CTO without the wire in the lead.

If a subintimal/subadventitial position is attained beside the true lumen, reentry is performed. The Stingray™ balloon (BridgePoint Medical) is a 1 mm flat balloon with three exit ports: The distal exit port is used to place the balloon in position while the other two ports are 180 degrees opposed; one oriented to the lumen and the other toward the adventitia. Using fluoroscopy for directional orientation, the Stingray guidewire is used to penetrate the distal true lumen and gain guidewire position.

Safety devices

To be prepared for complications, certain equipment must be available. This includes covered stents and embolization coils to manage perforation, as well as thrombectomy devices in case of thrombosis.

If tamponade occurs, timely availability of transthoracic echo and pericardiocentesis kits is critical. The presence of hemodynamic support systems including intraaortic balloon pumps and/or percutaneous LVADs are extremely important in cases of shock or cardiac arrest.

Techniques

Wire Escalation

A workhorse wire with a standard working bend is loaded in an over the wire (OTW) balloon catheter or microcatheter and advanced as far into the occlusion as possible. Occasionally the working wire will find a microchannel and cross partly or completely across the occlusion.

If the wire buckles and does not advance beyond the proximal cap, remove the working wire. A soft, tapered hydrophilic jacketed wire such as the Fielder XT (Asahi) is the next choice. This should be shaped with a 45-degree, 1 mm tip. If after 60 seconds the wire does not cross the occlusion directly, another wire is chosen.

The next wire choice depends on the characteristics of the CTO segment. If the occlusion is relatively short and seemingly well defined, a heavy weight, high puncture force CTO-specific crossing wire such as the Confianza Pro 12 (Asahi) should be used.

If the occlusion is tortuous and the path is ill-defined, a jacketed stiff tipped wire such as the Pilot 200 (Abbott Vascular) can decrease the chance of perforation outside the vessel architecture. Once the wire appears to cross the distal cap, careful confirmation of the intraluminal position is critical before continuing.

Angiography should be performed in at least two orthogonal views before the antegrade wire is advanced. Once a microcatheter or balloon is advanced beyond the CTO distal tip, balloon angioplasty and stenting can then be performed per usual practice.

Kissing wire: The retrograde wire is placed in the true lumen distal to the CTO, then advanced into the CTO. The antegrade wire is advanced using the retrograde wire as a target. This technique improves orientation and decreases contrast exposure.

Dissection reentry

The main tools for this strategy include the Crossboss or a knuckle wire. The goal is to advance antegrade through the subintimal space. To knuckle a wire, a looped wire is advanced without rotation. It is important to manage the size of the loop, or the knuckle, as creating too large a space can result in an intramural hematoma, making it difficult to successfully reenter. The adventitial distensibility, likened by some to an inner tube, accommodates blunt objects such as a looped wire or the cross boss while remaining susceptible to perforation with sharp objects such as high gram wires. It is important to avoid small branches using this technique.

Reentry-based or device-based

A stiff guidewire, such as the Confianza, is directed toward the true lumen. The stingray balloon appears as two radiopaque ports that can be identified on fluoroscopy.

Orienting oneself based on the markers, a wire is advanced through the true lumen to “stick” through the intervening tissue. A nontraumatic wire may then replace the initial wire so that distal wiring may be accomplished without additional trauma to the vessel.

Controlled antegrade and retrograde tracking (CART/Reverse CART)

A controlled dissection is used as a bridge to connect the proximal and distal true lumens by bypassing the occlusion. This strategy consists of an antegrade and retrograde wire, both advanced into the CTO lesion. A balloon is advanced retrogradely and inflated, disrupting the architecture and creating a connection between the 2 spaces.

Once the retrograde wire is in the true lumen it can be advanced into the anterograde guide catheter or captured with a snare. A 330 cm length ViperWire is useful in this setting as it has the length to traverse the intracoronary distance from the retrograde guide through the collaterals and then become externalized through the anterograde guide, providing support for subsequent PCI.

Appropriate balloon size is important for the success of this endeavor; intravascular ultrasound (IVUS) may be helpful to determine the necessary dimension. The strategy may be performed with an anterograde balloon inflation as well (reverse CART).

Algorithm

This comprehensive strategy allows for efficiency and success of an otherwise lengthy and sometimes frustrating procedure. Two guide catheters are placed to allow for dual coronary injection.

Simultaneous injection is extremely important to assess the distal cap and to identify collaterals. It is important not to pan during the initial picture to allow for easier identification of the collaterals and their course. Also of importance is the ability to delineate the vessel in a retrograde manner, decreasing the opportunity for hydraulic enlargement of a dissection plane during antegrade injection in the setting of dissection reentry.

The initial guide shots, as well as previous diagnostic film should be carefully analyzed; ad hoc CTO PCI is strongly discouraged. The initial views will aid in determination of the primary and alternative strategy.

The most important characteristics to note when studying a CTO are (1) identification of the proximal cap, (2) lesion length, (3) presence of branches as well as size and quality of the distal cap, and (4) suitability of collaterals.

First, determine whether the lesion length is less than or greater than 20 mm. Occlusions greater than 20 mm are associated with increased procedure times and decreased success rates, and may benefit from an alternative technique from the primary.

A hybrid approach anticipates that almost all cases may be completed in either an antegrade or retrograde fashion and the equipment and strategy take that into account. If the lesion is short (<20 mm) and has a clear proximal cap, antegrade wire escalation is the procedure of choice. This can be easily followed as a four-wire strategy using the main wire characteristics.

If the lesion is long but the proximal and distal cap remain clear, antegrade dissection reentry should be the primary strategy. If there are poor distal targets or ambiguous access, a retrograde approach may be tried initially.

It is of utmost importance to remain flexible in alternating between strategies. Using a benchmark of 5 to 10 minutes per strategy will aid in the decision to abandon one plan in favor of another. The goal is efficiency as well as success, which includes decreased time, radiation, and contrast use.

Outcomes (applies only to therapeutic procedures)

Compared with bare metal stents, drug-eluting stents improve the long-term patency of CTOs that are successfully opened. To date, however, no large randomized clinical trial has demonstrated a mortality benefit to opening of CTOs versus medical therapy, though several observational analyses suggest this.

Alternative and/or additional procedures to consider

Further escalation of medical therapy or CABG can be considered if a CTO cannot be crossed.

Complications and their management

The periprocedural complication rates of CTO are similar to that of non-CTO PCI. There are, however, complications and risks that are more common or specific to CTO cases.

Dissection is a complication that may be encountered in any PCI case. It is important to recognize the complication and be familiar with treatment options; these may be treated conservatively or with stent placement.

Thrombosis is more common with CTO cases, specifically involving the retrograde (donor) vessel. Prevention of this complication is paramount, and keeping the activated clotting time (ACT) greater than 300 seconds is key.

Perforation is the third major complication involving vessel injury. It is usually of less consequence when involving only a wire, but becomes a bigger issue when larger equipment, such as a microcatheter, exits the vessel.

When involving the main vessel, perforation is usually readily apparent. It can quickly lead to tamponade or cardiac arrest, so timely occlusion, reversal of anticoagulation, stat evaluation by echo, and potential covered stent placement are very important.

This is one of the reasons that heparin, with its potential for reversibility, is preferred over anticoagulation with bivalirudin. If a distal branch or vessel perforation occurs, it may be more subtle, and can be treated with embolization.

Tamponade with distal perforation can be a late presenting complication. Use of septal collaterals carries a lower perforation risk compared with epicardial collaterals. It is recommended that operators do not attempt using epicardial collaterals until they have become very experienced with septal crossing, as perforation and resulting tamponade are an inherent risk. There is less risk of frank tamponade in post-CABG patients due to the disruption of their pericardium.

Complications such as contrast reactions and access issues are nonspecific for CTO and should be managed traditionally. Radiation-induced skin injuries are more strongly associated with CTO cases due to increased procedure and fluoroscopy times. The preventive measures include:

Limiting fluoroscopy, using a lower frame rate and non-magnified views
Varying the image-intensifier angle
Using the fluoro store capability to limit cine
Monitoring dose—when reaching 6 to 8 gray air kerma dose, consider stopping the procedure if the lesion has not yet been crossed
Injecting the donor vessel before stepping on the pedal

Program/skill development

Complex CTO revascularization can be performed safely and successfully. While experience with non-CTO PCI does not necessarily translate to success with CTO, mentorship by experts, mastering the techniques, and understanding the algorithm greatly increase the chance of success.

Developing a strong CTO program requires implementation of quality and performance guidelines and knowledge of appropriateness. Skills including wiring of collaterals, antegrade dissection/reentry, and experience with retrograde techniques comprise a large learning curve and take time to master.

Of course, it is extremely important to understand the risks and complications; and to have both an informed operator and patient. The website www.ctofundamentals.org has been developed to be a resource for those interested in pursuing CTO PCI, offering lectures, resources, and community support.

What’s the evidence?

Joyal, D, Thompson, CA, Grantham, JA, Buller, CEH, Rinfret, S. “The retrograde technique for recanalization of chronic total occlusions: a step-by-step approach”. JACC Cardiovasc Interv. vol. 5. 2012. pp. 1-11. (This is a detailed technical guide to retrograde CTO PCI.)

Werner, GS, Schofer, J, Sievert, H, Kugler, C, Reifart, NJ. “Multicentre experience with the BridgePoint devices to facilitate recanalisation of chronic total coronary occlusions through controlled subintimal re-entry”. EuroIntervention. vol. 7. 2011. pp. 192-200. (This is the first publication regarding controlled antegrade dissection and reentry.)

Mehran, R, Claessen, BE, Godino, C. “Long-term outcome of percutaneous coronary intervention for chronic total occlusions”. JACC Cardiovasc Interv. vol. 4. 2011. pp. 952-61. (Supports the mortality benefit of CTO PCI.)

Galassi, AR, Tomasello, SD, Reifart, N. “In-hospital outcomes of percutaneous coronary intervention in patients with chronic total occlusion: insights from the ERCTO (European Registry of Chronic Total Occlusion) registry”. EuroIntervention. vol. 7. 2011. pp. 472-9. (Reviews the European experience in regards to outcome and improvement in success rates across a wide array of operators and the variability in approach based on operator.)

van der Schaaf, RJ, Claessen, BE, Vis, MM. “Effect of multivessel coronary disease with or without concurrent chronic total occlusion on one-year mortality in patients treated with primary percutaneous coronary intervention for cardiogenic shock”. Am J Cardiol. vol. 105. 2010. pp. 955-9. (Evidence of CTO as a predictor of mortality in this high risk population.)

van der Schaaf, RJ, Claessen, BE, Hoebers, LP. “Rationale and design of EXPLORE: a randomized, prospective, multicenter trial investigating the impact of recanalization of a chronic total occlusion on left ventricular function in patients after primary percutaneous coronary intervention for acute ST-elevation myocardial infarction”. Trials. vol. 11. 2010. pp. 89(Ongoing study demonstrating the mortality benefit of CTO PCI in patients who have had a STEMI involving another vessel.)

Saeed, B, Kandzari, D, Agostoni, P. “Use of drug-eluting stents for chronic total occlusions: a systematic review and meta-analysis”. Catheter Cardiovasc Interv. vol. 77. 2010. pp. 315-32. (Meta-analysis of the patency rates and outcomes of CTOs treated with drug-eluting stents.)

Joyal, D, Afilalo, J, Rinfret, S. “Effectiveness of recanalization of chronic total occlusions: a systematic review and meta-analysis”. Am Heart J. vol. 160. 2010. pp. 179-87. (Meta-analysis of successful versus failed CTO PCI, demonstrating improvements in mortality and quality of life with reduction in myocardial infarction with successful recanalization.)

Grantham, JA, Jones, PG, Cannon, L, Spertus, JA. “Quantifying the early health status benefits of successful chronic total occlusion recanalization: results from the FlowCardia's Approach to Chronic Total Occlusion Recanalization (FACTOR) trial”. Circ Cardiovasc Qual Outcomes. vol. 3. 2010. pp. 284-90. (One of many studies demonstrating improvement in quality of life following CTO PCI revascularization.)

Claessen, BE, Hoebers, LP, van der Schaaf, RJ. “Prevalence and impact of a chronic total occlusion in a non-infarct-related artery on long-term mortality in diabetic patients with ST elevation myocardial infarction”. Heart. vol. 96. 2010. pp. 1968-72. (Data emphasizing CTO as a major predictor of adverse events in diabetic patients.)

Banerjee, S, Master, R, Brilakis, ES. “Intravascular ultrasound-guided true lumen re-entry for successful recanalization of chronic total occlusions”. J Invasive Cardiol. vol. 22. 2010. pp. 608-10. (Niche antegrade technique to improve acute CTO PCI outcomes.)

Wu, EB, Chan, WW, Yu, CM. “The confluent balloon technique–two cases illustrating a novel method to achieve rapid wire crossing of chronic total occlusion during retrograde approach percutaneous coronary intervention”. J Invasive Cardiol. vol. 21. 2009. pp. 539-42. (Niche technique to improve retrograde dissection and reentry in resistant lesions.)

Thompson, CA, Jayne, JE, Robb, JF. “Retrograde techniques and the impact of operator volume on percutaneous intervention for coronary chronic total occlusions an early U.S. experience”. JACC Cardiovasc Interv. vol. 2. 2009. pp. 834-42. (First U.S. study of CTO PCI, which shows both the learning curve of CTO PCI as well as that high procedural success rates can be achieved in the U.S.)

Kimura, M, Katoh, O, Tsuchikane, E. “The efficacy of a bilateral approach for treating lesions with chronic total occlusions the CART (controlled antegrade and retrograde subintimal tracking) registry”. JACC Cardiovasc Interv. vol. 2. 2009. pp. 1135-41. (Seminal paper on the description of retrograde dissection and reentry, and its benefits to CTO PCI.)

Claessen, BE, van der Schaaf, RJ, Verouden, NJ. “Evaluation of the effect of a concurrent chronic total occlusion on long-term mortality and left ventricular function in patients after primary percutaneous coronary intervention”. JACC Cardiovasc Interv. vol. 2. 2009. pp. 1128-34. (This paper demonstrates that, in the setting of an STEMI, a second vessel with a CTO is the biggest predictor of acute and chronic mortality.)

Sianos, G, Barlis, P, Di Mario, C. “European experience with the retrograde approach for the recanalisation of coronary artery chronic total occlusions. A report on behalf of the euroCTO club”. EuroIntervention. vol. 4. 2008. pp. 84-92. (The first paper describing the European experience adopting retrograde techniques and the wide variability among the operators' use and techniques.)

Safley, DM, House, JA, Marso, SP, Grantham, JA, Rutherford, BD. “Improvement in survival following successful percutaneous coronary intervention of coronary chronic total occlusions: variability by target vessel”. JACC Cardiovasc Interv. vol. 1. 2008. pp. 295-302. (The first paper to suggest that the vessel involved may predict mortality [in this case the LAD artery]. Subsequent papers have demonstrated that revascularization of RCA and LCX artery CTOs may also improve mortality.)

Kirschbaum, SW, Baks, T, van den Ent, M. “Evaluation of left ventricular function three years after percutaneous recanalization of chronic total coronary occlusions”. Am J Cardiol. vol. 101. 2008. pp. 179-85. (Demonstrates that revascularization of a CTO supplying hibernating myocardium leads to improvement in left ventricular function.)

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