Looking at the Multi-Level Disease of Critical Limb Ischemia (CLI)

Disclosure: Dr. Mustapha reports he is a consultant for Bard, Covidien, Cordis, CSI, Spectranetics, Boston Scientific, Cook, and Terumo. Dr. Diaz-Sandoval reports he is a consultant for CSI. Dr. Saab reports he is a consultant for Terumo, Cook, CSI, Covidien, Spectranetics, and Bard. Dr. Adams reports he is a consultant for Cook Medical, Daiichi Sankyo,  Lake Region Medical, Volcano, Asahi, Abbott Vascular, CSI, Medtronic, and Terumo. He is a speaker for Abbott Vascular, CSI, Cook Medical, Medtronic, and Spectranetics. He has received research support from Boston Scientific, CloSys, Daiichi Sankyo, Flexible Stenting Solutions, Medtronic, Volcano, and Mercator. 

The authors can be contacted via Dr. J.A. Mustapha at jihadmustapha@aol.com.

Three scientists with a special interest in the complex nature of critical limb ischemia (CLI) discuss what it takes to achieve successful outcomes during the therapeutic course. First, Dr. Larry Diaz shares the importance of access for crossing chronic total occlusions (CTOs) in both above- and below-the-knee interventions, as well as his experience with multiple CTO devices. Dr. Fadi Saab discusses the analysis of CTO cap composition and the morphological appearance of plaque under ultrasound. Finally, Dr. George Adams describes his vast experience with CTO crossing wires and his algorithmic decision-making process to determine which wire to use and when to use it.

I. Crossing CTOs: Access and 

Device Use

An interview with Larry J. Diaz-Sandoval, MD, Metro Health Hospital, Wyoming, Michigan.

J.A. Mustapha, MD: What percentage of your peripheral vascular practice involves CTO treatment?

Larry Diaz-Sandoval, MD: Anywhere from 33 to 50%.

J. Mustapha: What is your preferred approach to treat superficial femoral artery (SFA) CTOs: contralateral retrograde common femoral artery (CFA) (“up and over”) or ipsilateral antegrade CFA? 

L. Diaz: The access strategy depends on many factors, but in general, I prefer to use the ipsilateral antegrade, ultrasound-guided CFA access to treat SFA CTOs, unless they are ostial.

J. Mustapha: What access do you prefer for ostial SFA CTOs?

L. Diaz: Contralateral retrograde CFA (“up and over”). In patients in whom this approach is not feasible, we frequently utilize retrograde tibialpedal access at our institution.

J. Mustapha: Do you treat SFA CTOs from an upper extremity access in obese patients?

L. Diaz: We have rarely used radial and/or brachial artery access exclusively to treat CTOs in the proximal one-third of the SFA. These have been patients where the “up and over” approach was not available (due to tortuosity, previous endovascular aneurysm repair, occluded contralateral iliac, etc.) and the tibial pedal approach was not an alternative.

J. Mustapha: Why just the proximal one-third?

L. Diaz: There are several reasons. The most commonly found hurdle when attempting to cross SFA CTOs from an upper extremity approach is the limited availability of devices with enough shaft length. The steep angle from the aorta to the subclavian and innominate arteries creates a significant deconstruction of the force vector applied to crossing devices introduced from an upper extremity approach. The loss of force leads to a significant decline in pushability and trackability, qualities of paramount importance for success in crossing and treating these lesions.

J. Mustapha: What is the cut off at which you would not approach an SFA CTO from the upper extremities?

L. Diaz: First, let it be clear that upper extremity access should not be the default access to treat SFA CTOs. A good rule of thumb is to simply avoid any lesion that is located beyond a point where we would not be able to deliver a covered stent (to successfully address the potential worstcase scenario of a severe perforation that fails to improve with repeated prolonged percutaneous transluminal angioplasty).

J. Mustapha: What size sheath do you start with during your SFA CTO crossing?

L. Diaz: Since the majority of the patients I treat with SFA CTOs are approached via an ipsilateral antegrade access, I tend to start with a 5 French (Fr) sheath. 

J. Mustapha: Do you find 5F to be sufficient for complex SFA CTO crossing?

L. Diaz: At our site, we have learned that most SFA CTOs can be successfully crossed with 5Fr compatible tools including CTO crossing devices such as the Crosser (Bard PV), Viance (Covidien), TruePath (Boston Scientific), FrontRunner (Cordis), and all support catheters.

J. Mustapha: What about the Wildcat?

L. Diaz: The Wildcat (Avinger) is an excellent CTO crossing device; however, it does require the use of a 6Fr sheath.

J. Mustapha: Do you have a preferred CTO crossing device?

L. Diaz: I don’t. Based on our vast experience with CTO cap analysis, we have learned that not all CTOs are created equally, and therefore, we allow the CTO cap itself (based on its morphology and composition) to call for the adequate crossing device.

J. Mustapha: Interesting. What do you mean by letting the CTO choose the crossing device for you?

L. Diaz: Over the last 5 years, we have been analyzing CTO cap morphological composition. We have found that based on the morphology and composition of both the proximal and distal cap, we can select the most adequate access strategy (antegrade, retrograde tibial-pedal, or combined antegrade-retrograde), and the tools that will be most likely to provide successful crossing and treatment of the CTO.

J. Mustapha: Which re-entry devices do you use?

L. Diaz: It depends on the location of the re-entry point, as well as the size of the target vessel, the amount of calcium in the arterial wall, and the size of the subintimal space. Depending on these variables, we choose the Outback (Cordis), the Enteer (Covidien), or the OffRoad (Boston Scientific). Sometimes we have to use an antegrade-retrograde approach and inflate a small balloon to serve as the target to the re-entry needle of the device being utilized (particularly when the size of the subintimal space is such that the distance between the re-entry device and the target re-entry vessel is larger than the size of the needle). Once the needle is delivered into the balloon, the re-entry wire is fed into the collapsing balloon and the balloon is removed from the access entry point. This creates a “rail” over which treatment can then be delivered.

II. CTO Cap Composition Analysis and Plaque Morphology

An interview with Fadi Saab, MD, Metro Health Hospital, Wyoming, Michigan.

J. Mustapha: We learned from Dr. Diaz that your team has been working on a CTO cap morphological analysis. Can you explain to us what you have learned and the name of your study? What imagine modalities have used to evaluate the CTO caps?

F. Saab: Identifying the CTO cap morphology is the first step in determining what vascular access will be required.  We are currently conducting the C-TOP trial evaluating types of CTO caps based on angiography and ultrasound (US). US mapping can directly visualize the CTO borders if the calcium content is low. We can also take advantage of the power Doppler and pulse wave Doppler mode to define the edges of the cap.

J. Mustapha: Is there one imagining modality that you prefer over the others?

F. Saab: Ideally, having US mapping of the CTO cap will better define the edges.  Patients with multiple CTOs limit the amount of contrast that opacifies the vessel.  Even with digital subtraction, pressure within the distal vessels may not allow the vessel to be opacified. Having US can offer additional information such as calcium content and collateral blood flow.

J. Mustapha: Does calcium presence in the intima, media, or luminal calcium affect the decision on how you approach a CTO crossing?

F. Saab: Certainly. Fluoroscopy remains a poor modality to define the location of calcium. It has been our experience that acoustic shadowing with US reflects more of an intimal calcium deposition, especially with the proximal and distal CTO caps, while in-between the CTO caps, we deal with mostly medial and adventitial calcium.

J. Mustapha: How many types of CTO caps have you found in the C-TOP study?

F. Saab: We have found a total of 4 types. The best way to describe the types is summarized in Figure 1. We designed the C-TOP classification with the idea that most operators approach CTOs from a contralateral retrograde CFA access.

J. Mustapha: What was the basis for the numbering of the different types?

F. Saab: The C-TOP classification depends on the simple concept of cap appearance.  Concave vs convex cap appearance will dictate if it is easier to cross into the true lumen or become subintimal. Depending on the combination of the proximal and distal CTO caps, 4 types can be found.

J. Mustapha: Is it fair to say that some CTO caps are easier than others to cross?

F. Saab: Absolutely. Take type I, for example. The proximal CTO cap is concave and the distal CTO cap is concave. The operator modality of crossing the CTO (CTO device, catheter, and/or wire technique) will have a better chance of crossing the CTO, because of the concave nature of the proximal and distal CTO caps directing your modality of crossing into the true lumen.

J. Mustapha: You treat a high number of CLI patients. Do you see the multi-level CTO as problematic during the revascularization process?

F. Saab: This is a significant problem and a challenge for a lot of operators. Since we adopted the use of extravascular ultrasound (EVUS), we found that long CTOs tend to have multiple, complex lesions. It is common to have CTO segments within the long CTO itself. We can visualize wires and catheters getting deflected in an antegrade or retrograde fashion. It is important to recognize that possibility. It is our experience that with longer CTOs, the operator is more likely to require alternative access and advanced re-entry techniques.

J. Mustapha: Do you see a difference in cap composition between supragenicular and infragenicular CTOs?

F. Saab: The jury is still out.  We partnered with Dr. Virmani to attempt to answer this question.   We observed that the concentration of calcium within tibial vessels is higher and more prevalent than in supragenicular vessels.  Acoustic shadowing under ultrasound is an important observation that we associate with severe calcification. That is more notable in tibial vessels. Another observation in tibial vessels is the presence of islands of calcium. This has a particular appearance on fluoroscopy (Figure 2). We describe this phenomenon as the CAST sign (CAlcification Separating Tibial arteries).

J. Mustapha: Why is easier to cross CTOs from tibial retrograde approach? Or is that just a myth?

F. Saab: The C-TOP analysis has confirmed that we are able to cross in a retrograde fashion in 25% of cases. This correlates with the rate of type IV CTOs (26.7% of CTOs). Depending on the type of CTO, we required pedal access in 82% of our CTO cases. In cases where there is reconstitution of the CTO in tibial vessels or at the distal portion of P3 of the popliteal artery, tibial access is a must.

J. Mustapha: In your practice, especially for limb salvage procedures, why do you start with dual access, including tibial retrograde and ipsilateral antegrade?

F. Saab: The common practice is to attempt in an antegrade fashion and see what happens. Our approach is quite different.  We typically start with CFA antgrade access and retrograde tibial access in 28.5% of cases. When we evaluated the rate of access conversion, meaning starting with antegrade access and obtaining pedal access later during the procedure, it occurred in 30% of cases.

J. Mustapha: Do you believe it should be a routine approach to limb salvage procedures?

F. Saab: I think the accumulating body of evidence falls in favor of this approach. We are cautious in advocating pedal access unless first, the operator, and second, the team, is comfortable with treating CLI patients. Having adequate equipment and most importantly, recognizing any complication and treating it promptly, is very important.

J. Mustapha: How much time, radiation, and contrast are you willing to spend on a complex limb salvage procedure?

F. Saab: I recognize there are no clear guidelines governing this process. A common mistake is to insist on finishing the whole procedure in one episode. CLI patients are complex and have multi-level disease. They may require multiple procedures to provide a sustainable result that guarantees wound healing. However, generally speaking, we avoid fluoroscopic time beyond 60 minutes. In addition, there are multiple equations that suggest a volume cutoff of contrast. These tools are not perfect and should not be a substitute to important measures such as hydration and discontinuing nephrotoxic agents.

J. Mustapha: Do you see the staging of these complex procedures becoming more acceptable in the vascular communities?

F. Saab: Absolutely. This is in recognition of the complexity of the revascularization procedures. We have to keep in mind that CLI patients have multiple comorbidities limiting their ability to tolerate long procedures. This is also an important conversation that we always have with our patients about expectations.

J. Mustapha: What is your prediction for success in CTO crossing over the next 5 years — will it become easier or more difficult?

F. Saab: I think we are starting to see more difficult and challenging cases. However, I am hopeful that with rapidly evolving revascularization and CTO crossing technologies, we will be better equipped to tackle these challenging cases. I am also very confident that pedal access and US utilization is a game changer in this complex field.

J. Mustapha: Why do you think it may get more difficult?

F. Saab: While I believe that we made significant improvement in our medical therapy regimen, our patient population continues to age. In addition, diabetes mellitus is becoming an epidemic that impacts a large number of our patient population. Patients are holding us responsible and asking the tough questions. We see many patients that are seeking a second opinion, because they are refusing amputation. I think our patients are challenging the old dogma of  “there are no options and amputation is the only way to treat”. We as a medical community have to rise and meet the needs of our patients.

J. Mustapha: Do you have a go-to CTO crossing device?

F. Saab: No, my approach is similar to what Dr. Diaz mentioned. Also, in light of the aging population, the complexity of the CTO caps, and the presence of severe calcifications, it is difficult to create a “cookie cutter” approach to CTO crossing. It is more like an evolving art that is constantly changing. We have to change, too, just so we can keep up with all the challenges that come along with it.

J. Mustapha: When it all fails and you have to reenter, what devices do you use?

F. Saab: Understanding the limitation of re-entry devices is important. There are multiple pros and cons to each. The Enteer Re-entry System (Covidien) is an excellent low-profile tool, but I find it limited when the media, in particular, is heavily calcified or the device is more than 4mm away from the true lumen. The OffRoad Re-entry Catheter System (Boston Scientific) is another good tool, but requires pre-dilation of the subintimal track to deliver it into the desired location. The traditional re-entry devices such as the Outback Re-entry Catheter (Cordis) or Pioneer Plus (Medtronic) are great tools. The Outback provides a 7.0mm and the Pioneer up to 11.0mm needle. Both devices can be difficult to deliver in a traditional retrograde CFA access. We have utilized the Enteer in a retrospective fashion. The 2.75mm device can be used through 4Fr sheath.

J. Mustapha: What is “Re-Back”?

F. Saab: This acronym stands for revascularization utilizing antegrade Outback re-entry into retrograde balloon. This is an advanced technique we utilize mainly in the SFA/popliteal vascular beds. Typically the antegrade wire is in a subintimal space or in the CTO itself. The retrograde wire is also in a subintimal space or in the CTO itself. The operator will utilize the needle from the Outback and point it in the direction of the retrograde balloon (typically 3.0-3.5mm x 120mm). The goal is to puncture the retrograde balloon and advance the wire from the Outback into the retrograde balloon. Once the balloon is punctured, contrast extravasation is noted and the tip of the needle is within the balloon. The Outback wire should be advanced swiftly. Once the antegrade wire is advanced to the retrograde balloon, negative pressure should be applied and the balloon will collapse over the antegrade wire.  This, in turn, created a snare system where the antegrade wire can be withdrawn to the true lumen from retrograde access.

III. The Use of CTO Crossing Wires

An interview with George Adams, MD, Director of Cardiovascular and Peripheral Vascular Research, Rex Hospital, Raleigh, North Carolina.

J. Mustapha: Can we assume all coronary wires will function in the same manner when used in tibial vessels?

G. Adams: No. First, tibial lesions are usually accompanied by lesions in the popliteal and/or SFA arteries. Therefore, a guide wire in the tibials needs to be able to traverse the lesions in the more proximal vessels while retaining its performance for crossing the tibial lesion. Second, tibial vessels often contain significant levels of luminal and subintimal calcium, which is relatively uncommon in coronary lesions. Many coronary wires will not have stiff enough tips to cross tibial vessels. A hydrophilic, polymer-coated tip is often useful for sliding through microchannels. In addition, tibial vessels may have longer lesions that require intra-lesion torquability to cross the distal cap. 

J. Mustapha: Is there a difference in the type of wire composition for traversing non-CTO tibial vessels? 

G. Adams: Yes. Some non-CTO lesions will allow for an .018-inch wire that can offer superior pushability and device delivery support to a .014-inch wire. Also, a coil-tipped wire may be advantageous due to the increased tactile feel vs a polymer-tipped wire that would be better for sliding through microchannels in a CTO. A wire that has both poly- and coil-tipped ends would be advantageous over a wire with one or the other type of tip.

J. Mustapha: When you think of an atraumatic tip wire, what types of wires come to mind?

G. Adams: Low gram tip, coil tip, usually about 1gm or less. Many coronary and neuro wires have gram tip loads below 1gm.

J. Mustapha: What makes a wire tip atraumatic?

G. Adams: Many things make a wire tip atraumatic, including:

a. Diameter of the wire. The lower the diameter of the core’s final barrel at the distal tip, the lower the gram tip load and the more atraumatic the wire. 

b. Gram tip load. The gram tip load is dependent upon the core material, the spring tip, and the diameter of the core at the tip. Nitinol wires of the same diameter will have lower tip loads than stainless steel wires cores of the same diameter. A coil attached at the tip adds to the tip load and support.

c. Hydrophilicity. Guide wires that are uncoated have the least lubricity and the most difficulty sliding through microchannels. Guide wires with a hydrophilic coating have less tactile feel, but can slide through channels more easily.

d. Coil vs polymer tipped. Coil-tipped wires are more atraumatic than polymer-tipped wires, and are less apt to perforate a vessel.

J. Mustapha: Can you explain gram tip load further?

G. Adams: The gram tip of a wire is the stiffness of the distal 10mm. To measure the gram tip of a wire, a computerized force tester with the wire is advanced through a fixture and the force the distal tip exerts when buckled is measured. A force curve is generated and the buckling load is electronically collected.

J. Mustapha: Are CTO wires better utilized with a supporting catheter or independently, and why?

G. Adams: With a supporting catheter. It increases gram load by a factor of 4, centers the wire, and provides support, especially when traversing calcified lesions.

J. Mustapha: When crossing tibial CTOs, how many wires are too many? 

G. Adams: Coronary stainless steel wires will get beaten up and misshapen when banging against calcified CTOs. Nitinol wires are often superior in tibial lesions due to their non-kinking characteristics. In some patients, a collateral artery may be needed for retrograde access to the softer and potentially better-shaped distal cap of a CTO. Therefore, a wire, like a neuro wire, that can go through a very tortuous pathway and reverse direction to go retrograde is needed. These wires have a long transition zone/grind profile, often with two or three tapers and barrels. Their lateral support is relatively low and is measured from the distal tip to the proximal, unground end of the wire. Grinding the core of the wires gives the wire its overall shape, and torque and trackability profile. Lateral support can be measured by pushing the wire down in increments of 0.5cm. The result is a function of the thickness of the wire where measured and its material. A nitinol wire has lower lateral support than a stainless steel wire, but this could be preferable because it does not take a set to traverse the anatomy. Wires that traverse collaterals often have very atraumatic tips that might not be able to cross the distal or proximal cap. A double-ended wire with an atraumatic tip used to gain access to a lesion and then allow utilization of a stiffer tip might be optimal. I have used up to 20 wires to cross a tibial CTO. My go-to wire is a Cook Approach 18gm. If that is unsuccessful, I may try a poly-tipped Victory wire 18gm (Boston Scientific). I then escalate the gram tip until I get to 30gms. It would be valuable to have double-ended wires that “self-escalate”, such as a wire with 18 and 30gm, or 40 and 60gm tips with shorter grind profiles.