Update on the Novel AV Reversal Therapy for End-Stage CLI
Introduction
J.A. Mustapha, MD
End-stage critical limb ischemia (CLI) is what we refer to as patients who have had revascularization attempts and are still facing major amputation. These patients are also referred to as Rutherford 6. During recent presentations at the 2016 Amputation Prevention Symposium (AMP) and 2016 Vascular InterVentional Advances (VIVA) conferences, Dr. George Adams and Dr. Jihad Mustapha presented data from the LIBERTY trial that showed 78% of Rutherford 6 patient were discharged home within 27 hours after endovascular revascularization, without limb loss. Their 30-day follow-up visit showed a similar high number of patients with their target limb still intact. Is it time to reconsider the fate of patients with Rutherford 6 and consider drastic forms of revascularizations prior to major amputations? Dr. Steven Kum of Singapore believes that patients with end-stage disease can still benefit from a unique procedure called arterial venous flow reversal. Dr. Kum, a vascular surgeon, developed an endovascular procedure to not only create the fistula, but also allow the venous conduit to arterialize over time.
J.A. Mustapha, MD: Can you explain the arterial venous flow reversal (AVR) concept?
Steven Kum, MBBS: Thanks, Jihad, for the invitation to contribute. Well, essentially, if we have an arterial system that cannot be opened, we preferentially pressurize the venous system and route oxygenated blood flow through this system. It’s a little analogous to traffic between two cities. Should a freeway be unserviceable in one direction, we hop over to the other side of the road to take advantage of the undiseased path (i.e., the veins) to reach where we want to go. This flow is reversed not only in the major veins, but also the smaller veins in the foot.
Dr. Mustapha: Can you explain the physiological changes that happen and the time frames for the changes?
Dr. Kum: Flow reversal is not a new concept. It is still occasionally done in the coronary system during a coronary bypass when the surgeon has to perform retrograde perfusion. There have been many reports in the past of surgical venous arterialization and contemporary surgical series are encouraging. We are still trying to understand the physiological changes. Immediately after flow reversal, arterialization of the veins and pressurization of the venous system occurs. We believe that this pressurization leads to oxygenation of the capillary bed.
Dr. Mustapha: To date, how many cases have been performed at your center and how many do you predict have been performed worldwide?
Dr. Kum: We have performed just under 15 cases in our center, but I have been closely involved in several European centers with a U.S. feasibility trial starting soon this year. I anticipate that as we push beyond the extreme interventions that we are already now doing, we are in a sense victims of our own success and will see more of these patients with end-stage disease. Preventing amputations saves legs and lives, but together with better medical therapy, our patients are surviving longer and have more severe disease every time we re-intervene. This may offer a solution for the global CLI pandemic.
Dr. Mustapha: Can you describe the technical procedure and give an understanding of the end results?
Dr. Kum: We have started using the LimFlow system (LimFlow SA) to do percutaneous deep venous arterialization (DVA) for several years now. The AV flow reversal leads to DVA.
Essentially, after antegrade 7 French (F) access and retrograde 5F venous access under ultrasound guidance, we do a double injection angiogram of both the artery and the veins at the intended area of crossing between the artery and the vein (the “crossover point”). After sufficient pre-dilatation, a 7F catheter (the “A” catheter), housing an ultrasound-emitting crystal is introduced into the artery in an antegrade fashion and positioned adjacent to the crossover point. Similarly, a 5F venous catheter (the “V” catheter), housing an ultrasound-receiving crystal, is introduced via the retrograde 5F sheath and positioned adjacent to the “A” catheter. With the help of a computer system, the 2 catheters are aligned. A needle system moves between the artery and vein followed by a wire, creating the arteriovenous fistula (AVF). The AVF is then ordinated and matured with a covered stent. Subsequent covered stents are used to serve as an endovenous conduit to drive a large volume of blood to the ankle. These covered stents serve to cover the numerous venous branches/collaterals that may “bleed off” the flow towards the heart rather than down to the foot. A key obstacle to the blood flowing to the foot is the valves in the foot. These impediments are, in my opinion, best addressed with a valve cutter. The team at LimFlow has designed a unique tool to address this issue percutaneously.
Dr. Mustapha: How do you determine if a patient is a good candidate for the procedure?
Dr. Kum: We must remember that the patients we have selected are end-stage CLI patients. This implies that they have no reasonable endovascular or open surgical bypass options for revascularization. As peripheral arterial disease is a systemic disease, we would expect the same disease process in the other vascular beds. Coupled with the advanced age of these patients, we could say these patients are fragile. Clinical selection of these patients relies heavily on good old clinical evaluation and some tests. In general, heart function should be more than 40%, and renal function reasonable. The extent of soft tissue loss and infection should not be too severe and we rely on the Society of Vascular Surgery Wound, Ischemia and foot Infection (WIfI) classification system to guide us on the suitability of these patients.
In addition, several other angiographic and sonographers criteria should be met. The target vein for retrograde access should be greater than 3 mm in size, and the inflow artery just proximal to the crossing point should be greater than 3.5 mm in diameter, especially in calcified vessels. This means that aggressive pre dilatation of the inflow vessels is essential.
Dr. Mustapha: Have you considered performing the AVR procedure on patients with Rutherford 5?
Dr. Kum: In our initial experience, we started treating end-stage patients as we deemed that these patients had no other alternative. As our technique and experience with the procedure has grown, we have started treating patients who are not end stage. A consideration would be to offer the procedure to someone who required a specific angiosome to be revascularized. Percutaneous DVA would be able to reperfuse the specific angiosome, sparing a non-contributory angiosome from potential restenosis. In my opinion, this holds promise, as we leave existing collateral circulation alone.
Dr. Mustapha: Do you follow a specific post-operative follow-up algorithm?
Dr. Kum: Post procedure, we encourage the continuation of therapeutic anticoagulation for 48 hours. Closure devices are regularly employed post procedure to allow this. Intravenous antibiotics are continued as per institution protocol. In general, we err on the side of caution and prefer a longer course of intravenous antibiotics due to the large amount of covered stent implanted, especially if the foot wound is infected. In anticipation of foot swelling, which is a sign of successful venous perfusion, we elevate the foot for 48 hours and ambulate the patient thereafter.
Dr. Mustapha: What is your advice to operators who are considering doing arterial venous flow reversal in their institutions?
Dr. Kum: There is a learning curve and the LimFlow device makes it much simpler to perform. It is absolutely crucial that these centers have good wound care programs. Venous arteriolization, in my opinion, is able to perfuse the foot. Wound care is somewhat different from a standard arterial revascularization (the details which cannot be covered here). As with all programs, a dedicated team will ensure that a good angiographic result translates to a good clinical result. This is especially true in percutaneous DVA.
Dr. J.A. Mustapha can be contacted at jihad.mustapha@metrogr.org. Dr. Steven Kum can be contacted at stevenkum.dr@gmail.com.
