Michael J. Glasby,1 George Markose2
and Amman Bolia2
1Derby Royal Infirmary, London Road, Derby, UK
2Leicester Royal Infirmary, Infirmary Square, Leicester, UK
Address for correspondence:
Dr. Michael J. Glasby MBBS BSc MRCS FRCR
X-ray Department, Derby Royal Infirmary
London Road, Derby DE1 2QY, UK
Tel: +44 (0)1332-340131
The technique of subintimal angioplasty (SIA) has been in use for approximately two decades and is a suitable alternative to bypass surgery. It was originally described in the femoro-popliteal arteries but its scope has been extended to occluded vessels throughout the body from crural vessels to visceral arteries. SIA is a straightforward and easy technique to master but there is a learning curve. The procedure is well tolerated with a low complication rate and is comparable to conventional angioplasty. Initial technical success rates are high (74-92%). Reported long-term patency rates are variable but assisted patency rates can be as high as 64% at 5 years. In cases where SIA has failed, repeated studies show that it does not jeopardise future surgery. The procedure of SIA is still evolving: recent developments include devices to aid re-entry back to the true lumen and stent technology to assist long-term patency rates.
Prior to the advent of subintimal angioplasty (SIA), endoluminal recanalisation could and can still be attempted. This may be the preferred option in very short occlusions or where the anticipated re-entry zone for subintimal angioplasty is short or heavily diseased. However, for longer or heavily calcified lesions this technique may be difficult or unsuccessful. Therefore familiarity with SIA offers the operator with an alternative approach and the ability to deal with inadvertent dissections. Although surgical bypass has favourable patency and limb salvage rates, many patients in this group have significant co-morbidities such as ischaemic heart disease, diabetes, respiratory disease and renal dysfunction. Therefore, the advent of a minimally invasive, simple and inexpensive alternative to open surgery in the form of SIA represented a revolution in the management of occlusive arterial disease.
It is now nearly 20 years since SIA was first described in the lower limb vessels . Despite this and numerous subsequent clinical studies, it has only relatively recently gained widespread clinical acceptance . Initially applied to the femoropopliteal segments, the technique has been extended to crural vessels , iliacs , coronary  and mesenteric vessels .
The aim of subintimal angioplasty is to create a channel between the intima and the media by means of an intentional dissection and then to perform an angioplasty on this channel to enlarge it and maintain patency.
For lower limb occlusive disease, the puncture is usually an antegrade common femoral artery (CFA) puncture although antegrade and retrograde popliteal artery punctures have been utilised [7-9]. In the case of flush occlusions of the superficial femoral artery (SFA), the position of the puncture is critical in order to allow sufficient space to manipulate the guidewire and catheter within the CFA to create the dissection. Antegrade punctures are favoured over contralateral retrograde CFA punctures because the latter may suffer from inadequate catheter push and torque control in the presence of acutely angled aortic bifucations and iliac tortuosity. Procedural complications such as emboli are more easily managed if the more direct antegrade puncture is used.
A catheter is introduced proximally to the occlusion. In our institution, a 4F short catheter with an angled tip (Bolia mini-catheter, Terumo, Japan) is used. A 5F pre-dilating straight catheter (Van Andel catheter, Cook, UK) or 5F Cobra catheter may also be used. Prior to the dissection a 3000-5000 IU intra-arterial bolus of heparin is administered.
A hydrophilic angle tipped guidewire is then introduced and it is encouraged to form a loop by its natural tendency to do so when the tip abuts the occlusion (Figure 1). Once the looped guidewire advances in the subintimal space it will take a spiral course. The loop will also appear to be slightly wider in diameter to the anticipated native vessel lumen diameter. If the wire is endoluminal the course it takes will be straight and the loop will be narrow. The loop allows the stiffer part of the guidewire to be used to continue the dissection. If little or no resistance is felt when the wire initially enters the occlusion and/or there is a clinical history of acute onset or deterioration of symptoms, then the presence of acute thrombus should be considered. The procedure may need to be abandoned at this stage. To reduce the risk of peripheral embolus, the procedure should only be reattempted after a period of 6-8 weeks.
However, once the guidewire is within the dissection channel, very little resistance may be encountered. While maintaining the loop in the guidewire, the catheter is then advanced behind it. The importance of maintaining the loop needs to be stressed because if the loop is lost, the guidewire will not create a sufficiently wide subintimal channel and will also tend to go down collateral vessels or cause perforation.
Breaking back into the lumen
The guidewire will naturally tend to re-enter the true lumen when it again encounters normal patent vessel. Re-entering the lumen in a favourable location may be problematic when there is significant disease or heavy calcification in the vessel. It may be inadvisable to continue the dissection past major collateral vessels or into run-off branches. Successful re-entry into the lumen is usually heralded by a loss of resistance to the wire which will move freely into true lumen. This can be confirmed with injection of a small volume of contrast. There are now devices available to aid re-entry in difficult cases such as the Outback catheter (Cordis) and intravascular ultrasound (IVUS) guided Pioneer catheter (Medtronic, USA) although, at present, these are expensive.
The angioplasty is carried out with brief inflations of a balloon catheter - of an appropriate diameter for the vessel concerned - to a pressure of approximately 10-12 atmospheres. The whole length of the subintimal channel undergoes angioplasty with repeat angioplasty to segments that have residual stenosis. Persistent stenoses or elastic recoil are difficult to manage and may require stenting.
As well as anticoagulation with heparin, the use of vasodilators such as tolazoline or nitrates may be necessary in the presence of vasospasm. Most patients are prescribed aspirin (if they are not already being treated with it) but formal anticoagulation with drugs such as warfarin is not generally recommended. In our institution, the preference is that patients stop clopidogrel a week before undergoing angioplasty because of the increased risk of haemorrhage. However, this regime may vary if stenting is anticipated.
- Chronic occlusive arterial disease
- Getting out of perforations
- Failed percutaneous transluminal angioplasty (PTA)
- Dissection of native vessel in the presence of an occluded bypass graft
- Long diffuse stenotic disease, particularly in calcified vessels where the long-term patency of PTA is poor. In heavily calcified vessels, the subintimal plane offers the path of least resistance whereas conventional PTA can be very difficult
- Flush SFA occlusions where PTA is likely to be impossible (Figure 2)
- Reconstructing run-off vessels in the presence of popliteal or trifurcation occlusion (Figure 3)
The complications of SIA are essentially no different to PTA (see below).
Puncture site complications
The risk of local haematoma and false aneurysm is no different to the risk with conventional angioplasty. Retroperitoneal haematoma can occur but the risk may be increased after a high puncture. A high puncture may have to be performed for SIA of a flush occlusion in order to allow a sufficient length of patent CFA for manipulation of the catheter and guide wire to dissect into the SFA. In our institution, if a high puncture is made, a defined protocol is followed by the medical and nursing staff to minimise the risk to the patient. A ‘group and save’ test is carried out as the probability that the patient will require a blood transfusion is low. If the need for transfusion arises, cross-matching can therefore be done quickly. More frequent observations of the pulse/BP and clinical signs are taken and, increasingly, closure devices are used.
The risk of peripheral embolism in femoro-popliteal SIA is 5-8% . This is usually managed successfully by aspiration embolectomy. If this is not possible, the ‘push and park’ technique has been described  where the embolus is pushed into a single vessel, preferably a minor one, using the embolectomy catheter or balloon. This method relies on there being at least one other patent run-off vessel. If the embolus is large it may become lodged in the sheath tip and the ‘pull and park’  method has also been described. On removal of the sheath, the embolus will then tend to become lodged in the arterial puncture thus achieving haemostasis. However, these latter two methods are last resort measures and surgical embolectomy is occasionally required.
The risk of vessel perforation is higher for SIA than for conventional PTA with an overall risk of 5-8%. The risk of perforation is higher in heavily calcified vessels (often seen in patients with diabetes), increasing age and in smokers  Perforation does not preclude continuing with the procedure. In fact, a subintimal dissection can be used to treat perforations [12,13] By creating a dissection above the level of the perforation, it effectively creates an intimal flap that seals the defect. If perforation occurs during SIA, then a new dissection channel must be made to exclude it. Furthermore, if there is a large perforation that does not seal spontaneously or by the above methods, coil embolization of the channel does not preclude a later reattempt at angioplasty, after a suitable delay of several weeks. A new subintimal dissection channel can then be made bypassing the embolization coils. Alternative treatment methods include balloon tamponade and covered stents.
Elastic recoil is a serious complication which threatens the patency of the recanalised vessel and will result in acute thrombosis of the subintimal channel. It should be suspected when the vessel fails to remain open despite repeated attempts at angioplasty. Fortunately, it is a relatively uncommon complication but can be unpredictable. Treatment includes the use of vasodilators, such as tolazoline (5 mg) or glyceryl trinitrate (50-250 µg); or deployment of long selfexpandable stents. The long-term patency of subintimal stents is variable and is discussed below [14,15]
Effectiveness of the technique has been measured in a number of ways in the literature. Procedural complications, mortality, limb salvage, patency and surgical intervention rates are favourable but to date there have been no randomised controlled clinical trials comparing the technique with surgical bypass and best medical therapy.
The initial technical success rate is high (74-92%). The evidence is that there is a learning curve to the procedure [16,17] with more experienced centres achieving better results  In critical ischaemia, SIA has been shown by Lipsitz et al.  to provide complete pain resolution in technically successful cases in 100% of patients, with gangrene healing in 84% of patients. Further evidence, at least in the short term, of the role of SIA in severe vascular disease in patients with few surgical alternatives has been provided by Kim et al.  In this study, there was an 83% limb salvage rate despite patients having anatomy unsuitable for bypass surgery and poor run-off vessels (and subsequently a relatively low 1-year primary patency rate of 52%).
The importance of surveillance programmes to increase the long-term patency of SIA has been highlighted by Florenes et al.  where 5-year primary patency rates of 54% increase to assisted patency rates of 64% in patients with intermittent claudication. SIA in infra-popliteal disease - a problematic group by any treatment modality - has also been studied. High technical success (78-86%) and limb salvage rates (81-94%) can be expected [19,20].
The length of the occlusion is an important risk factor for re-occlusion with long occlusions =10 cm in critical limb ischaemia having poorer results  Other risk factors for re-occlusion such as smoking and the number of calf run-off vessels and diabetes [22,23] have been identified. There is little evidence available of the value of antiplatelet drugs or anticoagulants in SIA patients to improve long-term patency. The use of aspirin plus clopidogrel in combination has been identified as an independent risk factor for both primary and assisted primary patency after stenting and the addition of warfarin also improved patency 
The routine use of stents in subintimal angioplasty has been investigated by a number of authors with varied reported success. Studies are difficult to compare because of different stent alloys and design. Indications for use also vary between different centres. Some centres reserve stent placement for recurrent occlusions/failed previous angioplasty, or where a suboptimal angiographic result has been obtained; other centres advocate routine use. Subintimally placed stents have even been placed alongside occluded endoluminal stents, so called ‘double barrel re-stenting’ 
Initial technical success rates of the order of 90% should be expected. Reported primary patency rates at one year are highly variable (22% to 76%) [15,16,25] Patency rates can be increased by surveillance and reintervention. As with SIA alone, the limb salvage rates are favourable. There is still no clear evidence to suggest whether the use of stents has a significant effect on long-term patency over SIA alone.
Stent-grafts provide a theoretically similar technical result to bypass surgery using synthetic graft material (although from a surgical perspective, these are less preferable to a vein graft). This has not been sufficiently assessed in the literature to justify its use routinely. The continued evolution of stent design will keep the debate on their use in the literature for some time to come.
SIA has extended the endovascular treatment options that can be offered for patients with occlusive arterial disease. The literature has repeatedly demonstrated it to be a safe and efficacious alternative to bypass surgery. This is particularly important in this patient subgroup who often have multiple co-morbidities that would increase the risk of surgical intervention. Familiarity with the technique also allows the operator to be comfortable with dealing with an inadvertent dissection or perforation which may occur in normal practice. Furthermore, there are very few contraindications to the technique that should dissuade the operator from offering this treatment to patients particularly as it has been shown that a previous attempted SIA does not jeopardise surgical treatment. The reported long-term vessel patency rates are variable but the limb salvage and symptomatic relief rates are very favourable. Although the technique is based on relatively simple principles, more experienced centres achieve better results. These results are improved further with surveillance programmes and early re-intervention. The use of stents as an adjunct to the technique continues to generate interest.
- Straightforward technique but there is a learning curve
- Virtually no contraindications and future surgery is not jeopardised
- Although reported patency rates are variable, limb salvage rates are very favourable
- Patency rates improve with surveillance and early re-intervention
- New technology of re-entry devices and stents may extend the role of SIA
- Bolia A, Brennan J, Bell PR. Recanalisation of femoro-popliteal occlusions: improving success rate by subintimal recanalisation. Clin Radiol 1989;40:325.
- Markose G, Bolia A. Subintimal angioplasty in the management of lower limb ischaemia. J Cardiovasc Surg 2006;47:399-406.
- Bolia A, Sayers RD, Thompson MM et al. Subintimal and intraluminal recanalisation of occluded crural arteries by percutaneous balloon angioplasty. Eur J Vasc Surg 1994;8:214-9.
- Bolia A, Fishwick G. Recanalization of iliac artery occlusion by subintimal dissection using the ipsilateral and the contralateral approach. Clin Radiol 1997;52:684-7.
- Taylor MA, Vetrovec GW. Angioplasty of a totally occluded right coronary artery. Cathet Cardiovasc Diagn 1992;25:61-5.
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- Yilmaz S, Sindel T, Ceken K, et al. Subintimal recanalization of long superficial femoral artery occlusions through the retrograde popliteal approach. Cardiovasc Intervent Radiol 2001;24:154-60.
- Higginson A, Alaeddin F, Fishwick G, et al. "Push and park": an alternative strategy for management of embolic complication during balloon angioplasty. Eur J Vasc Endovasc Surg 2001;21:279-82.
- Karkos CD, Dyer TG, Blanshard KS, et al. "Pull and park": an alternative means of achieving hemostasis in percutaneous aspiration thrombectomy of an arteriovenous fistula for dialysis. Cardiovasc Intervent Radiol 2006;29:164-5.
- Hayes PD, Chokkalingam A, Jones R, et al. Arterial perforation during infrainguinal lower limb angioplasty does not worsen outcome: results from 1409 patients. J Endovasc Ther 2002;9:422-7.
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- Ingle H, Nasim A, Bolia A, et al. Subintimal angioplasty of isolated infragenicular vessels in lower limb ischemia: long-term results. J Endovasc Ther 2002;9:411-6.
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- Duterloo D, Lohle PN, Lampmann LE. Subintimal double-barrel restenting of an occluded primary stented superficial femoral artery. Cardiovasc Intervent Radiol 2007;30:474-6.
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