Iliac Artery Disease: Pathophysiology, Diagnosis, and Management with Angioplasty and Stenting

INTRODUCTION

Peripheral arterial disease (PAD) is a complex disorder affecting arteries outside the heart and brain, primarily in the lower limbs. It can be stenotic, occlusive or aneurysmal disease of aorta, and branch arteries that may affect lower limbs, upper limbs, mesenteric, renal, and carotid arteries.^[1] It arises from a multifaceted interplay of factors compromising arterial health, including loss of arterial elasticity, abnormal platelet aggregation, and increased microvascular complications.^[2,3] Common risk factors are smoking, hypertension, diabetes, and hyperlipidemia. In a study conducted in India, dyslipidemia was not directly related to Ankle Brachial Index (ABI) in diabetic women despite indications from other researches done so far linking lipid abnormalities especially high-density lipoprotein with PAD.^[4]

As PAD progresses, it can lead to severe complications. Long-term effects often manifest as ischemia, characterized by absent pulses, cyanosis, non-healing ulcers, and intermittent claudication.^[5] Advanced stages may evolve into critical limb ischemia (CLI), potentially resulting in sepsis, amputation, and mortality. The iliac arteries play a key role in lower limb circulation, supplying oxygenated blood to the legs and pelvic organs. When these arteries become narrowed or blocked, typically due to atherosclerosis, it can lead to significant morbidity and reduced quality of life for patients.^[6]

Importantly, the prevalence and presentation of PAD differ between sexes. Women often present with atypical claudication complaints such as paresthesia and numbness or negligible symptoms, leading to underdiagnosis. Data from the Global Burden of Disease Study showed that PAD affects women more than men. This occurs across all age groups, particularly among younger women in low-income countries. PAD also affects women of non-white race compared to white race. Intriguingly, despite historically lower smoking rates among women, the prevalence of PAD is at least similar, if not higher, in women compared to men. This sex paradox suggests that sex-specific factors may contribute significantly to the pathogenesis of PAD in women.^[7] Effect of hormonal replacement therapy has been reported to have adverse effect on the patency rates of iliac angioplasty.^[8]

THE ILIAC ARTERIAL SYSTEM

The iliac arterial system consists of the common iliac arteries (CIAs), which originate from the abdominal aorta at the level of the fourth lumbar vertebra. CIA bifurcates into the internal and external iliac arteries (EIAs) on both sides. The internal iliac artery (IIA) supplies the pelvic organs, while the EIA continues as common femoral artery (CFA) to supply the lower limb.^[6]

Atherosclerosis is the primary cause of iliac artery stenosis or occlusion. This progressive disease involves the accumulation of plaque within the arterial walls, leading to several consequences:

1. Narrowing (stenosis) of the arterial lumen: This reduces blood flow to the lower limbs, causing symptoms such as claudication

2. Complete blockage (occlusion) of the artery: In severe cases, this can lead to CLI

3. Embolization: Pieces of plaque can break off and travel distally, causing acute ischemia in smaller arteries and can cause blue Toe syndrome

4. Arterial wall weakening: In some cases, this can lead to aneurysm formation.

The atherosclerotic process typically develops over many years, influenced by various risk factors as mentioned earlier. As the disease progresses, collateral circulation may develop to bypass the blockage, but these collateral vessels are often insufficient to fully compensate for reduced flow in the main iliac arteries, especially during exercise or in cases of severe stenosis.^[9]

The ABI is a key non-invasive test for diagnosing PAD. An ABI <0.9 is indicative of PAD, with lower values suggesting more severe disease. Exercise ABI can be particularly useful in detecting less severe cases.

Several imaging modalities can be used to diagnose and assess iliac artery disease:

• Duplex ultrasound: Provides information on blood flow and vessel anatomy^[10]

• Computed tomography angiography (CTA): Offers detailed anatomical information

• Magnetic resonance angiography (MRA): Provides better resolution images without radiation exposure

• Digital subtraction angiography: Considered the gold standard but is invasive. As there is risk of distal embolization a pre- and post-procedure lower extremity angiogram is very important

• Diagnostic aortoiliac angiography: The technique includes a 4F to 6F pigtail catheter kept above the renal artery. Injection of 20–30 mL contrast at the rate of 10–12 mL to see aortoiliac bifurcation. Usually, anterior-posterior view and occasionally 20–30° ipsilateral oblique view help in eccentric lesions. To see the relation between internal and external iliac vessels contralateral 20° and caudal 20° view helps. If possible, pressure gradient across the lesion should be taken. More than 30 mmHg indicates significant stenosis

• Intravascular ultrasonography (IVUS): It is a procedure that uses sound waves to detect narrowing and blockages from inside the blood vessels. Useful when ostial lesions cannot be excluded or we want to reduce the usage of contrast.

Aortoiliac atherosclerosis is associated with coronary artery disease; therefore, a detailed workup to rule out significant CAD should be done in all cases.^[11]

Mahé et al.^[12] (2015) proposed a diagnostic algorithm for IIA stenosis, which can be adapted for iliac artery disease in general:

1. Initial assessment with ABI

2. If ABI is normal or borderline, proceed with exercise tests (Exercise-induced transcutaneous oxygen pressure [TcPO₂] or Exercise-near-infrared spectroscopy [NIRS])

3. If exercise tests are positive or if initial ABI was abnormal, proceed to imaging studies (CTA or MRA)^[13]

4. Consider invasive angiography for definitive diagnosis and potential intervention.

This stepwise approach allows for efficient and accurate diagnosis while minimizing unnecessary invasive procedures. Figure 1 showing the algorithm for managing iliac artery stenosis.

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Figure 1:

Flowchart on management pathway for Iliac Artery Disease. (TASC: Trans-Atlantic-inter-society consensus classification, SES: Self expandable stent, BES: Balloon expandable stent, DCB: Drug coated balloon, CT: Computed tomography, DSA: Digital subtraction angiography, ABI: ankle brachial index, MR: Magnetic resonance)

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INDICATIONS FOR ILIAC ANGIOPLASTY AND STENTING

Iliac artery interventions are primarily indicated for patients with chronic limb ischemia caused by iliac artery occlusive disease. Intermittent claudication is the most frequent indication, accounting for roughly 65% of procedures. Patients typically experience significant limitation in walking distance or daily activities that persists despite conservative management.^[14] Another newer indication is vascular access as the iliac artery permits access to central circulation for coronaries and valves.

Patients considered for these procedures typically have evidence of significant arterial obstruction, with a median pre-operative ABI at rest of approximately 0.5 (range 0–0.9).^[15]

All patients with iliac artery disease might not require intervention. Those with mild symptoms may be managed conservatively with risk factor modification and exercise therapy. The decision to intervene should be based on the severity of symptoms, their impact on quality of life, and the overall risk-benefit profile for each individual patient. To make a strategy to treat the iliac vessel, it is important to know about trans-Atlantic-inter-society consensus (TASC) classification. Iliac artery lesions are classified by TASC,^[16] as shown in Table 1.

In recent guidelines for TASC A, B, and C lesions, endovascular treatment (EVT) is considered standard therapy and for type D lesions, surgical bypass is recommended.^[17] Lesion length affects the stent patency. Aortoiliac occlusive disease requiring longer than 61 mm stent has lesser patency rates.^[18] Stenosis of ipsilateral femoral artery (FA), gangrene, ulcer, renal dysfunction, and smoking are independent risk factors for long-term patency after intervention.^[19]

ILIAC ARTERY ANGIOPLASTY AND STENTING PROCEDURE EVT

The management of iliac artery stenosis continues to evolve, with percutaneous transluminal angioplasty (PTA) and primary stenting being two primary endovascular approaches.^[20,21] A review of randomized controlled trials provides insights into their comparative efficacy and safety, though with some important limitations.^[22]

The risk of immediate complications appears to be a critical consideration when choosing between PTA and primary stenting. The STAG trial, which focused on iliac artery occlusions, reported a significantly increased rate of major complications in the PTA/angioplasty group (20%) compared to the primary stent group (5%).^[12] This difference was primarily driven by a higher incidence of distal embolization in the angioplasty group. However, the Dutch Iliac Stent Trial, which predominantly included stenotic lesions, did not find major differences in complication rates between the two approaches.^[23]

In terms of efficacy, the review found no clear evidence of differences between PTA and primary stenting for several key outcomes.^[24] Technical success rates, symptomatic improvement, and patency rates were generally comparable between the two approaches across various time points. This suggests that both strategies may be viable options for treating iliac artery lesions, with the choice potentially depending on individual patient factors and lesion characteristics.^[23]

Figures 2 and 3 showing acceptable results of critical iliac stenosis after plain balloon angioplasty. Figure 1 showing planning strategy at a glance in flow chart. First, the strategy to address the lesion is planned. Depending on that access site, the hardware to give maximum control, push ability, and torque ability is decided. The procedure involves the following steps:

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Figure 2:

Diffuse atherosclerosis affecting aorta and bilateral ostial iliac artery disease with critical right iliac artery stenosis.

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Figure 3:

Acceptable result after balloon angioplasty. Green arrow shows the balloon angioplasty of the common iliac artery after balloon dilatation.

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Access and navigation

• Femoral access: Seldinger technique is used for FA access after giving local anesthesia. The entire process is monitored using X-ray imaging for accurate placement. Many operators prefer a micropuncture introducer kit nowadays to avoid local complications. Heparin is given in the dose of 50–100 units/kg body weight (usually 70 units/kg) to keep activated clotting time 220–250 s.

• Trans-radial access: Trans-radial approach is becoming increasingly common for patients as an alternative access site when FA access is not possible due to reasons such as prior surgery, body habitus, prior EVT on the CFA, or severe CFA disease like occlusion. Early ambulation is a big advantage of this route. The disadvantages of this approach for peripheral vascular intervention include decreased push ability and torque ability for long distance lesions. Radial spasm is another concern for which nitro-glycerine and diltiazem can be given through the sheath. These complications are increased with the use of larger sheaths.

• Trans-popliteal access: The trans-popliteal access is used for superficial femoral and popliteal artery vascular stenosis and occlusion but can be used for iliac artery intervention too. For these lesions, the popliteal access improves push ability and Torq ability. The complication rate is quite high^[25] with dissections, arteriovenous fistula and hematoma.

• Trans-pedal access: Posterior tibial artery access is essentially for popliteal lesions but can be used for iliac artery interventions too.

• Trans-brachial and trans-axillary access: In cases of bilateral lower extremity lesions, upper extremity access sites are useful.

The femoral retrograde route is most commonly adopted.

Selection of sheath and wire and balloon

Access and the approach determine the size and length of sheath. For radial access, it is advisable to use not more than 6 F sheath. For the more commonly used femoral approach can use a sheath size varying from 4 F to 24 F, but commonly used is 8 F. The longer sheath (70–90 cm) is used for contralateral approach, and shorter sheath (35–50 cm) for ipsilateral approach.

Antigrade approach, the operator has to put the sheath toward the flow, like from superficial femoral artery (SFA) toward opposite CIA, while retrograde approach means that sheath is put against the flow, like from SFA toward ipsilateral CIA and is used for the same target lesions, respectively.

The peripheral angioplasty wires commonly used are 0.035”, 0.018”, and 0.014” inches. The CIA and aortic interventions generally require 0.035” wire, which are thicker and stiffer and compatible with self-expandable stents. Hydrophilic wires are available if need be. Straight tip, J tip, or C tip as per operator’s comfort is chosen.

To prepare the bed for stent placement, a deflated balloon is threaded through the catheter to the blocked area of the iliac artery. Usually, the size of the balloon is 2 mm smaller than the reference vessel size to avoid distal embolization. Once in position, the balloon is inflated. This inflation compresses the plaque against the artery walls and widens the artery to restore normal blood flow. A smaller low profile 0.014’’ monorail coronary balloon with appropriate size can be used for very tight lesions. In other cases where the lesion is not very tight, a peripheral 0.035’’ balloon with size 4–6 mm and length of 20–30 mm can be used. Inflation should be slow to the tune of 1 atmosphere for 3–4 s and watching under fluoroscopy. One should stop inflation if the patient complains of discomfort or pain [Figures 2 and 4], and usually, prolonged inflation up to 1 min is required.

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Figure 4:

Pictorial representation of self-expandable stents and balloon expandable stents in iliac arteries.

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Stent choice and placement

After balloon angioplasty, the balloon is deflated and removed. A stent is then advanced through the catheter to the previously blocked area. The stent is expanded to press against the artery wall, keeping the artery open. Proper size and type of selection is important for stenting.

Balloon expandable stents (BESs) are good for focal and ostial lesions as they allow precise deployment. They usually are made of stainless steel or cobalt-chromium. They can pose difficulty while tracking very tortuous or calcified vessels due to their stiffness but the better radial strength is a stronger point in such lesions.^[26] They can cause artificial straightening of the vessel and promote neointimal hyperplasia. The maximum available length is 8 cm. If they are advanced without a long sheath, the stent can strip off the balloon. Sizes are 8–10 mm diameter and 20–30 mm length, while using BES keep them 2–3 mm into abdominal aorta to ensure ostial coverage. Figure 4 comparing BES and SES.

Long and diffuse soft plaques are better managed with self-expanding nitinol stents. These stents conform to vessel diameters and more adapt to arterial pulsatility.^[27] The usual size being 10 mm. The available lengths are longer up to 150 cm. The advantage of self-expanding stents is low risk of distal embolization and its ability to conform to vessel anatomy. The usual sizes are 7–10 mm for CIA and 5–8 mm in EIA.

Zigzag wire technique has been described in literature to negotiate hardware across previously deployed stents. Here bends are created on the wire to lift the balloon off the stent struts.^[28]

There have been few studies comparing balloon expandable stents (BES) with self-expandable stents (SES) in iliac arteries. iliac, common and external artery stent trial (ICE) Trial enrolled 660 patients and assigned them to BES and SES in 1:1 ratio. The result favored SES over a 12 months duration in lesser restenosis and lesser target lesion revascularization (TLR).^[29,30]

Covered stents (CSs) offer better patency rates but should not be placed across IIA.^[31,32]

Role of Intravascular Ultrasound (IVUS) in peripheral procedures

IVUS has been used in coronary interventions for almost a decade now. The optimization of viewing a lesion, from 2-D in angiography to 3-D in IVUS has generated interest among operators. The length, extent of calcium, stenosis severity, and the caliber of the peripheral artery can be better assessed through IVUS.^[33] Numerous studies support the use of IVUS in peripheral arterial interventions. Experts are reviewing the possible benefits in care and improvement in outcome with IVUS in PAD interventions.^[34]

It also decreases the radiation exposure to both patients and operators and also the non-ionic dye usage especially in patients with concomitant diabetes and or chronic kidney disease. The incidence of major adverse leg events has been reported to be statistically significantly lesser with IVUS in trials.^[34]

Complications of EVT include distal embolization, dissection, stent migration, and iliac artery rupture.

Availability of CS in and occlusion balloons in cath lab are important in cases of perforation. Vessel occlusion after stenting may occur especially if the vessel had dissection. Treatment of dissection is also to place a stent. Distal embolization or slow flow can be reduced by use of distal filters. Local lysis with infusion catheters can be useful in such cases.

SPECIAL SUBSETS OF PATIENTS

LATEST TRIALS

• To compare the clinical outcome of open bypass and EVT for aortoiliac disease, a meta-analysis of 5358 patients showed patency rate of surgery to be better than EVT but higher complication rate and mortality (18% vs. 13%). Hospital stay was also longer in surgical patients^[39]

• Another meta-analysis by Premaratne et al. in 2020 of 11 observational studies in 4030 patients showed primary patency rate over 50 months being better in surgical subset.^[40] The limb salvage rate was equal in both groups. When EVT was combined with femoral endarterectomy, the patency rates were better

• In EVT, only balloon angioplasty or BES, self-expanding stent, and CS has been used and studied so far

• STAG Trial by Goode et al.,^[41] was a randomized multicenter trial for patients with total occlusion of iliac arteries were enrolled. Stenting did increase the success rate and reduced distal embolization compared to balloon angioplasty^[18]

• Use of CS might improve the patency rates by reducing restenosis. The hypothesis being polytetrafluoroethylene cover on the stent acts as a direct barrier to neointimal hyperplasia and by excluding damaged endothelium from macrophages and blood-borne proinflammatory cytokines. Two-year results of DISCOVER trial compared CS versus Bare Metal Stents (BMS) in CIA, there was no difference in both arms in the outcomes.^[42] The freedom from restenosis was 84.7% in BMS versus 89.1% in CS group. This trial defined advanced CIA lesions as a stenosis which was longer than 3 cm.

• COBEST trial showed that CS had better patency rates over 5 years as compared to BMS.^[31]

Iliac angioplasty and stenting represent significant advances in the management of patients living with peripheral artery disease, as the field continues to evolve, staying informed about new developments and treatment options will enable healthcare providers to provide the best possible care and guidance to patients with PAD. The commitment to comprehensive care, ongoing education, and multidisciplinary collaboration will contribute significantly to the overall management of this challenging but treatable condition.

CONCLUSION

Future studies should aim to address the limitations of existing evidence and explore the potential of newer endovascular technologies in improving outcomes for this patient population. As our understanding deepens and technologies advance, we can look forward to more refined, personalized approaches to treating iliac artery disease, ultimately leading to better patient outcomes.