New Tools for Treatment of Chronic Total Occlusions of the Peripheral Arteries

History

It is estimated that 200 million people worldwide have peripheral arterial disease with 18 million Americans afflicted.¹ The annual cost for hospitalizations of patients with peripheral arterial disease in the United States is estimated to be in excess of $21 billion.² Left untreated, peripheral artery disease can lead to critical limb ischemia and as many as 160,000-180,000 patients with critical limb ischemia undergo amputation without angiography performed in over 50% of these patients. Up to 40% of patients with symptomatic peripheral arterial disease have chronic total occlusions (CTOs). Many of these occlusions are in the superficial femoral artery. As in the coronary arteries, peripheral CTOs may be challenging, leading to prolonged procedure time, increased radiation exposure, higher contrast utilization and peri-procedural complications, including dissection, creation of an arteriovenous fistula, or perforation. Revascularization is hindered with the inability to maintain the guidewire in the true lumen. Heavily calcified CTOs treated with standard techniques result in failure 20% of the time.³ As with coronary CTOs, understanding the course of the vessel and the location of collaterals is essential to success.  

Standard wire and balloon techniques result in intraluminal recanalization in 50% of cases depending on operator experience, lesion morphology, and location.³ More recently, subintimal angioplasty using a hydrophilic wire has had success rates approaching 80%.³ However, this technique requires operator experience as an important part of success. The importance of decreasing crossing time and consistent intraluminal positioning can be aided with some of the newer CTO crossing devices. Although the available devices in general are designed to remain in the true lumen, we now have subintimal tracking and re-entry devices to facilitate re-entering the true lumen. The pedal and popliteal approach has, in some cases, allowed us to be more aggressive in treating CTOs, knowing that we can always come from below to obtain an intraluminal successful recanalization with the retrograde approach. Here, we describe some of the technical and clinical aspects of the newer peripheral CTO devices. 

Crosser CTO Device

The Crosser CTO device (Bard Peripheral Vascular) is a unique system designed to achieve intraluminal penetration over long occlusions. It is approved for coronary and peripheral applications.⁴ The generator is controlled with a foot switch with a high frequency transducer and the Crosser catheter. High frequency vibrations are created and propagated by a stainless steel tip that facilitates penetration of hard, calcific lesions. It is available in .014-inch and .018-inch guidewire versions. The PATRIOT trial formed the basis for approval. In this study, after guidewire failure, the technical success was 84% with crossing of the peripheral CTO. The average lesion length was 117 mm with 75% of the lesions described as moderate to severely calcified.⁵  

TruePath

The TruePath catheter (Boston Scientific) is an .018-inch wire that rotates at 13,000 rotations per minute and the tip can be bent at 15% for steerability. The ReOpen study formed the basis for approval. In this study, the technical success was 80% with a safety endpoint of 98.8%. The mean lesion length was 116 mm and the time of device activation during the study was a mean of 8.2 minutes.³  

Avinger CTO Devices

The Avinger CTO device was originally approved as standard support for peripheral intervention. The smaller version includes the .014-inch Kittycat and Kittycat 2.

The Wildcat is an .035-compatible system with hydrophilic coating (inner cutter extended in lower picture). We find the Wildcat to be quite supportive and very useful in difficult chronic total occlusions (Figures 1A-E). It has become progressively improved, including the latest CTO version, the Ocelot device, which combines optical coherence tomography to image the CTO (Figures 2A-E).

Although these devices are clearly very sophisticated, calcific fibrotic lesions that, in the past, were thought to be more easily treated with hydrophilic wires, in fact, may be more easily crossed and more efficiently crossed with a stiff, very supportive .035-compatible device.⁶  

The Viance Device

The Viance device is a novel device developed originally from Bridgepoint Medical and now is marketed by Medtronic. This rigid device is composed of a crossing catheter for intraluminal recanalization with an .014-inch guidewire. We have found it to be very useful in resistant lesions in the coronaries and peripheral arteries. It is 150 mm in shaft length. The coronary version of the CrossBoss CTO catheter (Boston Scientific), the Viance was described in the FAST CTO trial as having 77% technical success, and fluoroscopy and procedural times significantly less than historic controls.⁷ The Viance device has also had excellent results with technical success of initial crossing without the use of a re-entry device achieved in 87.9% of cases and procedural success obtained in 82.6% of the time.⁸ The Viance CTO crossing catheter appears to cross infrainguinal arterial CTOs with high success, as well as low complications and significant symptomatic improvement. The CrossBoss was also developed with a re-entry device called the Stingray (Boston Scientific).

Re-entry Devices

The frustrating aspect of CTO intervention has been the fact that subintimal adventures can result in failure. Re-entry catheters are effective for advancing the guidewire from the subintimal space and puncturing back into the true lumen. The Outback catheter (Cordis) is advanced over a .014-inch wire. Using simple, orthogonally oriented radiopaque markings to direct a re-entry needle toward the true lumen under fluoroscopic guidance, the “L” and “T” helps orient the re-entry cannula toward the true lumen under fluoroscopy. A 22-gauge nitinolol cannula deploys into the true lumen, followed by wire passage. The needle is retracted and device removed. After balloon dilatation, stenting can be performed if indicated. The Pioneer catheter (Philips Volcano) is another re-entry catheter that is advanced over an .014-inch wire. The catheter is advanced subintimally, beyond the distal cap and adjacent to the site of reconstitution. With intravascular ultrasound (IVUS) guidance to orientate the re-entry cannula toward the true lumen, a nitinol needle is deployed into the true lumen, allowing the wire to safely enter the true lumen.  However, some of the new re-entry devices allow us to control our subintimal position and if not expanded, the Stingray, the Pioneer, and the Outback devices allow us to re-enter into the true lumen.⁹  

CenterCross CTO Device

A new category of devices have recently been introduced for CTO percutaneous coronary intervention, primarily initially as coronary CTO devices. The MultiCross and CenterCross (Roxwood Medical) have a stabilizing, self-expanding scaffold that is deployed proximal to the target lesion.10 The MultiCross contains 3 micro-catheters in the scaffold, each located 120 mm apart. The CenterCross has a single large central lumen that can accommodate a micro-catheter.

Prodigy and CrossLock 

The Prodigy (Radius Medical LLC) builds on the experience with anchoring balloons that have been utilized for over a decade in CTO work primarily in the coronaries.  

The Prodigy is an over-the-wire catheter with a distal elastomeric balloon, 5 mm long and 6 mm in diameter. This centers the catheter in the blood vessel, making the wire more likely to stay intraluminal. The balloon is inflated at low pressure (1 atmosphere) and the catheter has a very short tip (<2 mm) allowing for aggressive placement of the wire close to the occlusion.  This allows a much greater guidewire support system and assists with centering the wire, minimizing the risk of subintimal guidewire entry. The CrossLock (Radius Medical LLC) is an 8 French guide catheter-compatible system that can be very effective for chronic occlusions of the coronary and peripheral arteries, but with its 6 French sheath compatibility, is uniquely suited for peripheral CTOs (Figure 3A-C).¹⁰  

The CrossLock is the only peripheral device that allows not only centering of the catheter to maintain intraluminal positioning of .014-inch wires, but unlike any other peripheral device, it allows the CrossLock balloon to be inflated with super strong support for utilizing other devices for crossing CTOs or complex, resistant lesions, such as balloons, the .9 Spectranetics laser, the FrontRunner (Cordis), the Crosser, the Viance, and the CrossBoss.¹¹ We recently used the CrossLock to center the lumen to assist crossing with the FrontRunner device. The Frontrunner XP CTO catheter enables controlled crossing of CTO by using blunt microdissection to create a channel through the CTO to facilitate wire placement. It is designed to maintain the guidewire in the center of the lumen and penetrate the plaque in a controlled fashion. However, if the device tracks subintimally, a re-entry catheter may be needed to regain access into the true lumen (see two cases presented in Figures 4-5). All other peripheral devices need to be removed prior to the placement of these CTO devices.  

The CrossLock balloon is larger than the Prodigy balloon, in this case, 8 mm, and we found it has dramatically reduced our crossing times and therefore, procedure times, with a lower likelihood of needing a re-entry device. Although this technique is not FDA-approved, we have even used the CrossLock with the laser in a step-by-step manner in peripheral and coronary applications. The CenterCross, MultiCross, Prodigy, and CrossLock are all FDA approved.

Discussion

The good news is that we are making an impact in these patients. In a study of 642,433 admissions at the Cleveland Clinic in patients with critical limb ischemia, Agarwal et al¹² showed that between 2003 and 2011, there was a significant reduction in patients undergoing surgical revascularization (13.9% vs 8.1%), with interventional procedures increasing from 5.1% to 11% during the same time. Compared to surgical revascularization, endovascular revascularization resulted in reduced in-hospital mortality (2.34% vs 2.73%, P<0.001), mean length of stay (8.7 days vs 10.7 days, P<0.001) and mean cost of hospitalization ($31,670 vs $32,485, P<0.001) despite similar rates of major amputations (6.5% vs 5.7%, P=0.75).  

Conclusion

Our goal is to perform the procedures quickly, with less contrast, less fluoroscopy, and higher safety. We find that all of the CTO devices have some value. The CrossLock has a unique approach with its ability to center the catheter to make use of other crossing devices more effective. Hopefully, this technology will continue to improve with re-entry devices as our failsafe, so we can work aggressively. With improvement in our experience in the pedal approach, we know we can many times go from the foot if the aggressive approach from above is not successful. 

References

1. Sanguily III J, Martinsen BJ, Igyarto Z, Pham MT, et al. Reducing amputation rates in critical limb ischemia patients via a limb salvage program: A retrospective analysis.  Vascular Disease Management. 2016; 13E(5): E112-E119.
2. Kullo IJ, Rooke TW. Peripheral artery disease. N Engl J Med. 2016; 374:8861-8871.
3. Javed U, Laird JR. Specialty crossing devices: understanding the learning curve.  Endovascular Today. 2012 May. Available online at https://evtoday.com/2012/05/specialty-crossing-devices-understanding-the-learning-curve/. Accessed November 22, 2016.
4. Ali I, Butman S, Heuser RR. Crossing a chronic total occlusion using combination therapy with Tornus and FlowCardia. J Invas Cardiol. 2006; 18: E258-E260.
5. Joye J. The PATRIOT (Peripheral Approach to Recanalization in Occluded Totals) study results. Am J Cardiol. 2007; 100(suppl 1): S24.
6. Pigott JP, Raja ML, Davis T. A multicenter experience evaluating chronic total occlusion crossing the WILDCAT catheter (the CONNECT study). J Vasc Surg. 2012; 56(6): 1615-1621.
7. Whitlow PL, Burke MN, Lombardi WL, et al. Use of a novel crossing and re-entry system in coronary chronic total occlusions that have failed standard crossing techniques:  results of the FAST-CTO (Facilitated Antegrade Steering Technique in Chronic Total Occlusions) trial. JACC Cardiovasc Interv. 2012; 5: 393-401.   
8. Banjerjee S, Thomas R, Sarode K, et al. Crossing of Infrainguinal peripheral arterial chronic total occlusion with a blunt microdissection catheter. J Invasiv Cardiol.  2014; 26(8): 363-369.
9. Werner GS. The BridgePoint devices to facilitate recanalization of chronic total occlusions through controlled subintimal re-entry. Expert Rev Med Dev. 2011; 8(1): 23-39.
10. Brilakis ES, Galassi AR. Role of novel guidewire support devices for crossing coronary artery chronic total occlusions. J Invasiv Cardiol. 2016; 28(3): 92.
11. Heuser RR. Going to the front with the FrontRunner™ and the CrossLock™: a new treatment regimen in complex peripheral CTOs. Vascular Disease Management Blog. May 2016. Available online at https://www.vasculardiseasemanagement.com/blog/going-front-frontrunner-and-crosslock-new-treatment-regimen-complex-peripheral-ctos. Accessed November 22, 2016.
12. Argarwal S, Sud K, Mehdi H, Shishehbor DO. Nationwide trends of hospital admissions and outcomes among critical limb ischemia patients. J Am Coll Cardiol. 2016; 67: 1901.

Disclosure: Dr. Heuser reports he is the the co-developer of the CrossLock and is on the Board of Directors of Radius Medical.

Richard R. Heuser, MD, can be contacted at rheuser@phoenixheartcenter.com.