Endovascular intervention in Management of

Infrapopliteal Peripheral Vascular disease

• Incidence of infra- popliteal peripheral arterial disease (PAD) continues to rise

• aging population, higher diabetes, ESRD

• Historical experience with infrapopliteal surgical and endovascular intervention disappointing

• High rate of early technical failures and procedural complications

• High rates of restenosis in this vascular territory when compared with more proximal vascular beds.

• Patients with infrapopliteal PAD may be asymptomatic, the majority ultimately develop intermittent claudication or may present with critical limb ischemia (CLI).

• combined approach of medical therapy supplemented with revascularization (endovascular or surgical) of inflow disease (iliac and femoropopliteal) is the current standard of care and the acceptable initial strategy for revascularization

• Use of antiplatelet therapy (with or without anticoagulation), cilostazol, risk factor modification, exercise programs, and pain control

Infrapopliteal intervention versus

Above knee• Indication

• more likely to be CLI (critical limb ischemia) than claudication

• Arteries smaller in calibre and disease often extensive

• Patients more likely to have serious comorbidites such as diabetes mellitus and renal failure

• Different instruments required

• Restenosis is more common in infrapopliteal vessels than it is in more proximal vascular beds,restenosis is of less importance in limb salvage procedures.

• Tissue repair, in the context of CLI and nonhealing wound, is associated with high metabolic demands than a resting tissue and thus requires higher levels of oxygen and nutrition

• Successful infra- popliteal intervention will depend on the presence of good inflow and thus more proximal disease should be initially addressed.

• Goal of intervention - establishing straight line pulsatile flow to the foot

• Factor most affecting clinical outcome was the number of patent arteries after PTA (<30 % residual stenosis).

• One-year limb salvage rates for 0, 1, 2, and 3 patent infrapopliteal arteries after PTA were 56.4, 73.1, 80.4, and 83.0 %, respectively

• Greater the number of patent vessels after PTA, the higher the likelihood of functional limb salvage, restoring patency of one or both tibial arteries is generally preferred over patency of the peroneal artery alone.

• Peregrin JH, Koznar B, Kovac J (2010) PTA of infrapopliteal arteries: long-term clinical follow-up and analysis of factors influencing clinical outcome. Cardiovasc Intervent Radiol 33: 720–725

• Taylor and Minabe defined angiosome as a three dimensional anatomic unit of tissue fed by a source artery

• Attinger et al explored the concept of angiosome of the foot and ankle

• Six angiosomes originate from the three main arteries and their branches to the foot and ankle.

• three posterior tibial artery angiosomes fed by three main branches: the calcaneal branch (heel), the medial plantar artery (instep), and the lateral plantar artery (lateral midfoot and forefoot).

• two branches of the peroneal artery supply the anterolateral portion of the ankle and rear foot.

• anterior tibial artery supplies the anterior ankle, and its continuation, the dorsalis pedis artery, supplies the dorsum of the foot

• retrospective analysis of 52 surgical bypasses for lower extremity wounds divided the patients into those who had a direct revascularization (bypass to the artery feeding the ischemic angiosome) or an indirect revascularization

• Significant difference in wound healing rate was found in the direct revascularization group (91 %) versus a 62 % healing rate in the indirect group

• Neville RF, Attinger CE, Bulan EJ et al (2009) Revascularization of a specific angiosome for limb salvage: does the target artery matter? Ann Vasc Surg 23:367–373

• single-center retrospective data of endovascular treatment of CLI patients have found significantly improved results by using the direct revascularization approach

• Definition of success

• Technical

• Anatomic <30% final residual stenosis measured at narrowest point of vascular lumen

• Continued anatomic <50% recurrent stenosis

• Hemodynamic

• ABI or Thigh/brachial index improved by 1.0 or greater above baseline and not deteriorated by >0.15 from max early postprocedure level or pulse volume recording distal to reconstruction maintained at 5mm above the preoperative tracing (only in non compressible vessels)

• Clinical

• Immediate and sustained improvement by at least 1 clinical category

• Patients with tissue loss(Cat 5 & 6 ) must move up at least 2 categories and reach the level of claudication to be considered improved

Endovascular therapy versus surgery

• Critical limb ischemia (CLI) most compelling indication for intervention in the infrapopliteal bed

• Femorotibial bypass surgery (using a venous conduit) is the standard revascularization modality in preserving limb viability,

• surgical bypass surgery carries better immediate and long-term results in the setting of claudication than in CLI

• Success of bypass depends upon

• Presence of good outflow for the graft to remain patent,

• Availability of quality venous conduit

• Skills of an experienced surgeon.

• Presence of diffuse tibioperoneal disease, small-vessel diameter (<3 mm), or more distal anastomosis sites are associated with less favorable surgical revascularization results.

• patients with infrapopliteal disease usually have numerous comorbidities.

• surgical bypass surgery for infrapopliteal disease, in CLI, is associated with high perioperative complication rates (2%-5% mortality, 5%-10% hemorrhage, 7% graft thrombosis, and 20% significant wound infections).

• Most patients require long postoperative recovery time, with the risk of graft infection, graft thrombosis, distal embolization, and wound breakdown or infection.

• endovascular interventions have emerged as a valid and an attractive alternative to bypass surgery

Procedural considerations• Access

• Can be performed from contralateral aspect

• antegrade access is usually necessary to provide reach to more distal targets.

• Meticulous technique in antegrade sheath placement is essential in avoiding vascular access complications.

• A 5F or 6F, 30- to 60-cm sheath for balloon angioplasty

• 7F sheath for atherectomy

• Careful evaluation of the inflow circulation and of the infra- popliteal run offs is essential in planning a successful intervention

• Aortogram with lower extremity runoff with DSA to define burden of PAD in entire limb

• CT angiography not sufficient for analysis of distal vascular territories

• Selective femoropopliteal and tibioperoneal angiography is typically needed to assess the extent of tibioperoneal and pedal disease, the nature of the collateral circulation and the identification of chronic occlusions and reconstitution points in the distal run off

• nature of the lesions, the amount of calcium, the presence of total occlusion and the length of these occlusions, and the number of runoff vessels needs to be well understood and will play a major role in deciding what equipment will be needed for revascularization.

• Wire choice depends on nature of lesions

• No total occlusion

• 0.014” coronary wires - Cougar, Spartacore, Runthrough NS, Choice PT

• Total Occlusion

• Confianza, Miraclebros, Winn, Pilot via 0.014 inch catheter or low profile balloon catheter

• If unsuccessful

• 0.018” guide wire

• Glidewire Gold, Astato 30

• Crosser catheter

• high frequency ultrasound to cross total occlusion

• Principles of crossing similar to that in coronaries

• Central luminal(nonsubintimal) crossing more optimal and facilitate use of different endovascular devices

• Subintimal crossing techniques have been used successfully

Complications of infrapopliteal interventions1. Access-related complications (such as hematoma

and femoral artery dissections).

2. Tibial artery spasm, which is encountered occasionally (although less likely with low diameter wires) and is responsive well to intra-arterial vasodilators, such as nitroglycerin.

3. Tibial artery perforation, which can lead to compartment syndrome, is usually perceived by the patient as acute pain (which should alert the interventionalists to the possibility of adventitial dissection and perforation), is usually the result of aggressive guidewire manipulation, and can be effectively sealed with a pro- longed (5 minutes) low pressure inflation (5 atm) of a nominal-size balloon. In such circumstances, the reversal of anticoagulation is warranted.

4. Thrombus formation is unusual in this vascular territory provided that no flow-limiting dissection is encountered and left untreated and that appropriate anticoagulation is instituted.

5. Distal embolization (especially common with some of the atherectomy devices and may warrant the preemptive use of filter devices) and air embolism, which may result in a no-flow phenomenon, but generally is responsive to vasodilators and proper proximal revascularization.

6. Contrast nephropathy.

Endovascular devices

Percutaneous Transluminal Angioplasty

• Balloon angioplasty remains the gold standard therapy in this territory despite the limited data regarding the utility of percutaneous transluminal angioplasty (PTA) in infrapopliteal segment

• early PTA trials that reported no significant difference in the outcome between PTA and bypass surgery in patients with CLI.

• Wolf et al reported no significant difference, at a median follow-up of 4 years, between PTA and bypass surgery for iliac or femoral popliteal disease in the context of claudication or rest ischemia

• Bypass versus Angioplasty in Severe Ischemia of the Leg (BASIL) trial

• 450 patients with severe limb ischemia (rest pain, ulceration, and/or gangrene)

• due to infrainguinal disease

• PTA and surgery

• similar outcome in terms of amputation-free survival when compared to lower-limb bypass surgery (71% versus 68% with surgery).

• Surgery was associated with a significantly higher rate of morbidity in 30 days (57% versus 41% with PTA), and a significantly lower rate of reintervention (18% versus 26% with PTA).

• 20% immediate technical failure was reported in the PTA arm.

• Tibial artery is better approached with 0.014 or 0.018 inch wire.

• Balloon angioplasty typically is done with long (3-5 minutes) low-pressure inflation with the balloon sizes averaging between 2.5 and 4 mm in diameters

• balloon should be sized to the vessel on a 1:1 ratio,

• Smaller balloons initially in case of total occlusion

• Contralateral femoral access with subsequent crossover sheath placement in case of focal, nonocclusive lesion in the proximal infrapopliteal vessels.

• more complex lesions, total occlusion, diffuse lesion, and distal tibiopedal lesion, an antegrade sheath placement will be necessary for better visualization and reach

• Retrograde wiring through the distal tibial vessels, at the level of the ankle, has been successfully used.

• micropuncture needle is used to access the vessel, and 0.014- to 0.018-inch hydrophilic wire is advanced to cross the distal cap of the total occlusion.

Drug eluting balloons

• DEB are designed to release paclitaxel into the media at the site of angioplasty to reduce the restenosis due to neointimal hyperplasia by suppressing the proliferation of smooth muscle cells.

• DEB of size and length appropriate for the calf are now available

• DEBATE-BTK study

• A paclitaxel-eluting balloon was compared with a conventional balloon in diabetic patients with CLI undergoing angioplasty of tibial vessel lesions

• Restenosis occurred in 27 % of patients in the paclitaxel-eluting balloon group compared with 65 % in the conventional balloon group (p = 0.0004).

• Reocclusion was present in significantly more patients in the conventional balloon arm (53 vs. 16 %; p = 0.0006)

Atherectomy• Atheroablative atherectomy

• laser atherectomy, rotational atherectomy, and orbital atherectomy

• where luminal patency is achieved by ablation (fragmentation of the plaque into smaller particles)

• Excisional atherectomy

• Limited data regarding atherectomy in infrapopliteal interventions

• Encouraging results

• Use of atherectomy in the management of infrapopliteal PAD has many attractive implications

• Infrapopliteal vessels are generally small, usually calcified, and frequently chronically occluded.

• debulking these vessels, as opposed to compressing the existing plaque against the vessel wall withballoon angioplasty and/or stenting (which is likely to increase the intimal-medial hyperplasia), is postulated to minimize neointimal hyperplasia leading to less restenosis, and will carry a lower risk of dissection (especially in calcified vessels) and plaque shift (especially at the trifurcation of the popliteal artery and other branching points).

Excisional atherectomy

• Plaque excision with the SilverHawk System

• Approved by FDA in 2003

• The technical success rate ranged from 87% to more than 95%, with the need for bailout stenting at a rate of 4% to 6%, and a reported limb salvage rates ranging from >80% of 6 months to 70% to 92% at 12 to 18 months.

• Treating Peripherals with SilverHawk: Outcomes Collection (TALON), the largest multicenter (19 institutions) observational, nonrandomized, registry, 601 consecutive patients were enrolled (50% of which were diabetic).

• Plaque excisions were performed using the SilverHawk catheter on 1258 symptomatic lower extremity atherosclerotic lesions (748 limbs).

• The study included patient with above and below the knee lesions, who presented with claudication or CLI (nearly one third had Rutherford ischemia category of >4).

• Excellent procedural success rates were reported (97.6%) with a bailout stenting rate of 6.3%. The 6 and 12 months target lesion revascularization (TLR) rates were 90% and 80%, respectively.

• Zeller et al

• SilverHawk system specifically for infrapopliteal disease

• 3% of patients had CLI. They reported a primary patency rate of 73% and secondary patency rate of 91% at 18 months and a primary patency of 60% at 2 years.

Excimer laser• The Turbo Elite Laser Ablation catheter

(Spectranetics Corporation, Colorado Springs, Colorado) has been used in the treatment of infrapopliteal PAD in the context of CLI.

• multifiber laser catheter uses ultraviolet energy to photoablate obstructive and stenotic lesions

• Photoablation is the process by which energy photons are used to disrupt molecular bond at the cellular level without thermal damage to surrounding tissue

• Turbo Elite catheter has a lubricious coating to facilitate tracking.

• For the infrapopliteal segment, 0.9 to 1.7 mm catheter should be used over a 0.014-to 0.018-inch wire.

• In treating stenotic lesion, the catheter is passed slowly after activation (<1 mm/s), provided no resistance is encountered.

• Calcified lesions may require more pulses of laser energy than fibrosclerotic lesions

• not recommended to exceed 20 seconds of lasing

• For total occlusions, step-by-step technique is used, during which the catheter is advanced slowly (2-3 mm) into the total occlusion, following the guidewire path, allowing the laser energy to remove occlusive plaque.

• Catheter is then deactivated and the guidewire is advanced further into the occlusion and then the catheters reactivated again

• As the lesion is traversed, the final segment prior to the reconstitution of the vessel distally is crossed by the guidewire.

• Following atherectomy, PTA is usually necessary to achieve satisfactory results.

• Laser angioplasty for CLI phase II trial (LACI 2),

• 177 infrapopliteal lesions were treated with a reported limb salvage rate of 93% at 6 months. These data are compatible to that of the balloon angioplasty

Orbital atherectomy• The Diamondback 360 Orbital Atherectomy System, or OAS

• Ablative atherectomy device that uses an eccentrically weighted, diamond-coated crown, that orbits to preferentially ‘‘sand’’ calcium and other relatively noncompliant components of the target lesion.

• Ablated particles that would shower downstream have a mean diameter of 2 mm, reducing the risk of significant macro-embolization.

• Differential ablation of noncompliant tissue (such as calcified and fibrocalcific plaque) with the protection of compliant normal elastic vessel wall limits the likelihood of dissection and plaque shifting,

• Orbital atherectomy system for the treatment of PAD (OASIS)

• 24 patients with intermittent claudication or CLI were treated with OAS.

• Of the patients enrolled, 85% had infrapopliteal lesions, 39% had chronic total occlusions, and 32% had CLI.

• At 24 months, the rate of limb salvage was 100%.

• Bailout stenting was reported in 2.5% of patients only. The OASIS long-term study found that the rate of TLR was 8.7% and 13.6% at 12 and 24 months, respectively.

• CONFIRM study

• Real-world multicenter study, that prospectively followed 728 consecutive patients in 57 institutions treated with OAS

• OAS use was safe in the hands of various operators (more than 80 operators participated in the study) with a reported low adverse procedural events (0.5% perforations, 1.2% abrupt closure/no flow, 0.7% macro-embolization, and a 2.2% bailout stenting rate)

Combination revascularization

catheter• Jetstream G3 SF revasularization system

• Dual-action rotational atherectomy and thrombectomy

• 1.85-mm, front-cutting, high-speed (70 000 rpm), rotational atherectomy catheter with active aspiration port that allows for continuous aspiration of debris.

• recently approved by the FDA and has been used mostly in the SFA but will likely be ventured into the infrapopliteal territory as more experience with device grows.

Cryoplasty• theoretical advantage of cryoplasty is the controlled

induction of apoptosis in the vessel wall by the cold balloon, in the hope that smooth muscle cell proliferation and restenosis is reduced.

• Polar- Cath cryoplasty system is introduced through a 6F sheath over a 0.014-inch guide wire.

• Pressurized liquid nitrous oxide is delivered into the balloon, designed to give an outer balloon surface temperature of -10 °C.

• Cryoplasty of 111 limbs achieved a 97.3 % technical success rate. Stent placement was required in three patients. At 1 year, major amputation was avoided in 85.2 % of patients(Non randomised Chill trial)

Stents• Bare metal stents

• Successful use of small stents in coronary arteries, have led to their use in the infrapopliteal arteries.

• Some stents on the market that have been specifically designed for the calf vessels.

• Maris deep Invatec-Medtronic, x-pert Abbott

• only a single published RCT of BMS versus balloon angioplasty in the calf. This is a small, and underpowered trial of 38 limbs in 35 patients randomized to angioplasty or primary BMS.

• At 12 months, there was no statistical difference in survival, limb salvage or in primary and secondary patency rates

• BMS placement has therefore been recommended to be reserved for suboptimal results after angioplasty such as residual stenosis or flow limiting dissection.

• Drug eluting stents

• Several nonrandomized studies have reported promising outcomes of DES in the calf

• DES- TINY trial randomized 140 patients with CLI to the Xience V DES (everolimus) versus the Multi-Link Vision BMS

• Primary patency rates (no binary in-stent restenosis>50 %) were significantly better in the DES group (85.2 vs. 54.4 %), although limb salvage rates were comparable between both groups (98.7 vs. 97.1 %)

• BELOW study was a randomized trial involving 60 patients treated with either DES, BMS or PTA all in combination with abciximab, or PTA alone. There was significantly less restenosis in the DES group compared with the others

• ACHILLES trial

• 200 patients were randomized to either the Cypher Select DES (sirolimus) or PTA.

• 2 months, they found a significantly increased binary restenosis rate for the PTA group of 41.9 versus 22.4 % (p = 0.019) in the DES group

• Wound healing had a trend toward improved healing rates in the DES group (61.7 vs. 41.3 %, p = 0.06).

• Studies demonstrate a consistent benefit of DES over the comparator in terms of patency, and it seems likely that sound evidence of clinical benefit will emerge in due course.

• Current DES used in the calf were designed for the coronary arteries: DES designed specifically for the calf vessels are not as yet available.

• Early success of DES in the coronary arteries was tempered by the finding of an increased risk of late thrombosis, resulting in the need for long term DAPT

• This phenomenon has not been reported in the calf vessels, but extrapolating from the coronary experience, most authors consider dual anti- platelet therapy essential after DES placement in the calf

• Bioabsorbable stent

• magnesium-alloy bioabsorbable stent (Biotronik AG) was investigated, hypothesizing that they combine the mechanical prevention of vessel recoil without the per- manent presence of an artificial implant which could be a potential trigger for restenosis.

• 117 patients were randomized to either implantation of an absorbable metal stent or PTA alone.This generation of absorbable metal stent did not reveal any improvement in long- term patency over PTA

Guidelines