Invasive angiography remains the gold standard for the diagnosis of critical limb ischemia. Noninvasive vascular imaging studies, e.g., duplex ultrasonography, computed tomographic angiography, and magnetic resonance angiography, are also frequently utilized. Angiography with concomitant potential for ad hoc endovascular intervention offers an attractive option with reduced morbidity, especially in high-risk patients with coexisting coronary artery disease. Endovascular intervention can restore antegrade flow and aids in the healing of ischemic ulcers . It can also move the level of amputations more distally resulting in less morbidity.

Invasive angiography can be performed using small 4–6 F catheters with adequate visualization. To assess the lower extremities, access can be obtained from contralateral common femoral artery (CFA) (Fig. 20.1), antegrade ipsilateral CFA, radial artery, brachial artery, and rarely axillary artery. Contralateral arterial access and crossover remains the most utilized technique. In CLI patients, depending on the site of obstruction, catheter should be placed proximal to the lesion in order to visualize the collaterals, followed by selective stepwise angiogram (Figs. 20.2 and 20.3). Contralateral 30° angle during angiography will help visualize the iliac bifurcations, and ipsilateral 30° will open up the vessel below the external iliac artery.

Access can usually be obtained by feeling the femoral pulsations against the femoral head. If the pulse is not palpable due to severe disease or morbid obesity, access can be achieved under fluoroscopy using the bony land marks. The use of ultrasound has also been suggested in identifying the femoral artery, especially for antegrade access. A recent study comparing the time for antegrade common femoral artery access and safety between the ultrasound-guided access versus fluoroscopy-guided access showed that ultrasound-directed common femoral artery access was faster and safer [4]. Also, in a recent multicenter randomized controlled trial, routine real-time ultrasound-guided access improved common femoral artery cannulation in patients with high CFA bifurcations and also showed reduced number of attempts, less time to access, decreased risk of venipunctures, and less vascular complications [5]. During antegrade CFA access, ultrasound-guided technique is faster and safer compared to fluoroscopic technique.

In addition to defining the arterial anatomy, angiography can usually distinguish between two most common causes for CLI, i.e., atherothrombosis and embolism. Thrombus usually appears as sharp or tapered but not a rounded cutoff on angiography. Diffuse atherosclerosis along with collateral circulation is generally visualized too. An embolus usually has a sharp cutoff with a rounded reverse meniscus sign. An embolus may also be visible as an intraluminal filling defect if the vessel is not completely occluded. The presence of otherwise normal vessels, the absence of collateral circulation, and the presence of multiple filling defects are also signs of embolic phenomenon.

Iodinated contrast is most commonly used for angiography. Carbon dioxide (CO₂)-mediated angiography is utilized when there is coexistent chronic kidney disease in patients with PAD to decrease the risk of contrast induced nephropathy (CIN) . CO₂ angiography can also be utilized in patients with iodine contrast allergy. Due to a risk of embolism related to CO₂, it should be utilized with caution, especially if used for vessels above the diaphragm. In a recent prospective multicenter registry, the safety and efficacy of CO₂ angiography-guided endovascular therapy for renal and iliofemoral artery disease was assessed. Patients with an estimated glomerular filtration rate (eGFR) of <60 mL/min/ and stage 3 CKD were enrolled. Incomplete CO₂ angiograms were supplemented by intravascular ultrasound, pressure wire, and/or minimal iodinated contrast media. The primary endpoint was a composite of freedom from renal events and freedom from major CO₂ angiography-related complications. The study included 98 patients with 109 lesions. The mean eGFR at baseline was 35.2 ± 12.7 mL/min. The technical success rate was 97.9 %. The primary endpoint was achieved in 92.8 % (91/98) patients. Incidence of CIN was 5.1 %, and CO₂ angiography-related total complications occurred in 17.3 % patients including leg pain, abdominal pain, and diarrhea, and two patients developed severe, fatal, nonocclusive mesenteric ischemia.