V.A. is a 62-year-old male who presents in referral

, LLC an HMP Communications Holdings Company Clinical Case Update Latest Trends in Critical Limb Ischemia Imaging Amit Srivastava, MD, FACC, FABVM Interventional Cardiologist Bay Area Heart Center St. Petersburg, FL V.A. is a 62-year-old male who presents in referral from the wound care center for a poorly healing right first digit wound. This wound has been present for over six weeks and has not healed significantly. The patient s past medical history is significant for diabetes mellitus type II for over 30 years with associated peripheral neuropathy, coronary artery disease (CAD) status post-coronary artery bypass grafting and percutaneous intervention, peripheral arterial disease status post-left superficial femoral artery stenting, benign essential hypertension, atherogenic hyperlipidemia, and ongoing tobacco abuse. The wound care center obtained a computed tomography (CT) angiogram for ischemic evaluation. The CT angiogram was read as markedly abnormal. It detailed heavily calcified iliac arteries bilaterally with at most 50% of the common iliac artery stenosis bilaterally; 50% of the right common femoral artery; 60 to 70% left common femoral artery stenosis; 80% heavily calcified right superficial femoral artery (SFA) stenosis with poor contrast in the popliteal artery limiting interpretation with two-vessel runoff; and 80% proximal as well as distal left SFA stenosis with a widely patent mid-vessel stent, left popliteal artery subtotal occlusion, and two-vessel runoff to the left foot. Due to the poorly healing wound as well as established peripheral arterial disease (PAD), this patient was referred for peripheral angiography and intervention. Angiography was performed via the left femoral approach. Under ultrasound imaging, the patient s left common femoral artery was noted to have a subtotal occlusion distally. Access was obtained cephalad to the lesion in a healthy portion of the left common femoral artery using ultrasound guidance, micropuncture access, and microsheath insertion. Angiographic imaging found no significant aortoiliac stenosis or aortoiliac hemodynamic gradients. There was significant vascular calcification without obstructive lesions. The left common femoral artery was noted to have distal severely calcified 99% stenosis prior to its Figure 1. Critical right superficial femoral artery (SFA) and profunda femoris stenosis, which likely led to a critical limb ischemia presentation prior to intervention. bifurcation. The left SFA at the adductor canal was also noted to have another severely calcified focal 99% stenosis with three-vessel runoff to the left foot. The right common femoral artery was noted to have a distal 99% severely calcified stenosis that subtotally occluded the origin of the profunda femoris and totally occluded the right SFA. There was faint reconstitution of the distal right SFA via profunda femoris collaterals and three-vessel runoff to the right foot. Right SFA total occlusion revascularization was performed via atherectomy, angioplasty, and stenting. Post-intervention, the right lower extremity demonstrated brisk flow and preserved three-vessel runoff to the foot. The patient s right first digit wound was completely healed at the three-week follow-up appointment. 1

Figure 2. Left common femoral artery access site. Figure 4. Distal right SFA prior to intervention. Peripheral arterial disease affects over 200 million people worldwide. 1 With an increase in the aging population as well as the diabetic population, this number is expected to increase significantly over the next decade. As a result, there is a greater percentage of the population presenting with Rutherford stage III claudication or greater as well as critical limb ischemia (CLI). There are grave implications given the rise in patients with PAD. Nearly 25% of patients presenting with CLI are dead at one year with the majority of deaths due to cardiovascular causes. 1 Quality of life measures for these patients are comparable to those of patients with terminal cancer. Figure 3. Severe distal left SFA stenosis at adductor canal. A big question that healthcare providers are faced with is how to initially evaluate patients presenting with PAD. What is the best first test to assess the severity of PAD? Should angiography be considered directly? Is an ankle-brachial index (ABI) enough to quantify the severity of the disease? What are the limitations of the tests ordered? It is important to determine testing strategy based on clinical presentation. Are the tests performed to assess the severity of asymptomatic PAD detected on physical examination? Is the patient presenting with stable, intermittent claudication? Is the evaluation for CLI? In general, patients presenting with asymptomatic peripheral arterial stenosis or stable claudication can be safely evaluated as outpatients in a controlled, regimented fashion. Patients presenting with CLI represent a population in which time is of the essence, and they need more urgent assessment and treatment. The options available for evaluation include ABI, arterial duplex ultrasound, computed tomography angiography, magnetic resonance angiography, and conventional angiography. The decision regarding which test to use involves special considerations such as clinical presentation, urgency of evaluation, cost, and patient preference. Ankle-Brachial Index The ABI can be considered a first-line screening test for PAD or those patients with established cardiovascular disease such as CAD, carotid artery disease, or abdominal aortic aneurysms. ABIs should be performed to rule out coexisting PAD. This is calculated by dividing the higher of the systolic pressures between the anterior tibial and posterior tibial arteries in a lower extremity by the higher of the 2

Figure 5. Right SFA atherectomy. upper extremity systolic blood pressures. This test, however, has its limitations. Arterial calcification, as is expected in elderly and diabetic patients, can cause falsely normal and/or elevated ABIs due to reduced vascular compliance. This can be overcome by performing toe brachial indices (TBIs) that are more technician dependent and require specialized equipment. Pros: Quick; no cost Cons: Can be falsely normal or elevated in patients with calcified vessels and diabetes Arterial Duplex Ultrasound Arterial duplex ultrasound examination can provide both anatomic as well as physiologic evaluation. This test can be readily performed in the outpatient ambulatory setting, making it cost-effective while simultaneously providing timely results. A specially trained technician uses an ultrasound probe to scan the lower extremity arteries with gray scale imaging, power B-mode color Doppler, and spectral Doppler. Gray scale imaging provides anatomic information with regard to the amount of atherosclerotic plaque, plaque morphology, and the amount of calcification. Power B-mode imaging defines the direction of blood flow as well as providing qualitative blood flow assessment. Spectral Doppler imaging provides quantitative evaluation of phasicity of blood flow as well as stenosis severity. Grayscale imaging can be useful in determining anatomic locations of plaque burden. It can also assist in choices regarding treatment at the time of angiography and intervention. For example, if significant calcification is noted on grayscale imaging, the interventionalist may decide to use adjunctive atherectomy at the time of Figure 6. Proximal right SFA after intervention. intervention. Aneurysmal disease noted on grayscale imaging may change the treatment strategy altogether. Power B-mode imaging is useful in identifying whether total occlusions are present, collateral flow, and locations of bypass grafts. Identification of where collateralization reconstitutes a vessel can help the interventionalist determine access site and means of intervention. For example, low reconstitution of a vessel may cause the operator to plan on tibial/pedal access at the time of intervention. Spectral Doppler provides a wealth of information. Spectral phasicity can help determine vascular compliance as well as aortoiliac inflow disease. Triphasic spectral waveforms are seen in normal vessels with normal compliance. As compliance reduces, phasicity changes to biphasic. Monophasic waveforms are seen in aortoiliac inflow stenosis, in post-hemodynamically severe stenotic segments, and in severely calcified vessels with markedly reduced compliance. Additionally, the spectral velocities recorded provide quantitative information regarding stenosis severity. By using peak systolic velocity ratios 3

Cons: Technician-dependent, reduced sensitivity for aortoiliac disease, less spatial resolution and definition of anatomy when compared to other imaging modalities Figure 7. Distal right SFA after intervention. (PSVRs) to compare velocities in segments of interest to preceding segments, one can identify hemodynamically severe stenosis. For example, if a preceding non-diseased segment has a spectral velocity of 100 cm/s and the segment of interest has a velocity of 300 cm/s, the PSVR of 3 is indicative of hemodynamically significant peripheral arterial stenosis. Duplex ultrasound examination does have its own limitations. There is reduced sensitivity for aortoiliac inflow disease, as these segments are not visualized by the ultrasound. Sensitivity can be increased when performing baseline ABI in combination with post-exercise ABIs. If there is a significant reduction in post-exercise ABI, aortoiliac inflow disease is suggested. Additionally, the spatial resolution and definition of anatomy is significantly less than with other imaging modalities. Pros: Cost-effective, can be done in the office providing timely results, provides anatomic and physiologic information, can help the interventionalist in pre-case planning Computed Tomography Angiography CT angiography uses iodinated contrast to define vascular anatomy via timing of contrast bolus infusion with CT imaging. The studies are usually done in both non-contrast and contrast phases. They are often performed in outpatient radiology centers or hospitals, and less often in the outpatient office setting. The advantages of CT angiography are excellent spatial resolution and definition of anatomy. Precise measurements can be made regarding vessel size. In particular, when surgical bypass grafts or anatomic variation are present, the results can aid in revascularization by assisting in choice of access site. Also, calcification or particular plaque anatomy can help the interventionalist determine ahead of time whether specific measures such as atherectomy or tibial/pedal access may be necessary. Results are available usually within 1-2 days, and the studies are usually well tolerated by patients. There are distinct disadvantages to CT angiography as well. These studies are more costly than duplex ultrasound and often require prior authorization from insurers. This can add time and delay the evaluation of the patient. These studies use ionizing radiation and cumulative exposure can cause radiation-induced effects later in life. This can be a concern for patients wanting to limit their radiation exposure. Non-dialysis-dependent renal insufficiency and allergy to iodinated contrast are contraindications for this procedure. Severe vascular calcification and prior stent placement can cause beam hardening artifact and speckling artifact respectively, making assessment of stenosis severity significantly less accurate. In the presence of a severe, unilateral, hemodynamically significant peripheral arterial stenosis, contrast bolus image acquisition can be asymmetric, as the contrast will travel more slowly down the affected side, limiting image interpretation. Pros: Excellent spatial resolution; aids in intervention based on anatomic definition; quick study that is well tolerated by most patients Cons: More costly; delay in obtaining results; uses ionizing radiation; iodinated contrast issues; calcification limits stenosis severity evaluation; limited contrast image acquisition with asymmetric stenosis Magnetic Resonance Angiography Magnetic resonance (MR) angiography provides similar information as CT angiography. The particular advantage of MR angiography over CT angiography is that calcification does not limit stenosis severity evaluation. There are two means of MR angiography evaluation. The more common method of evaluation is using 4

flow to acquire vascular imaging. The major advantage of this procedure is that no gadolinium is used for acquisition of angiographic imaging. The disadvantages of MR angiography are unique to its image acquisition process. MRA acquisition can be uncomfortable for patients due to claustrophobia, as patients will need to be in a closed tube for 30-45 minutes. This can be seen in open MRI acquisition as well. Additionally, MRA imaging is generally more costly than CT angiographic imaging. Renal insufficiency is an absolute contraindication due to the risk of retroperitoneal fibrosis with gadolinium. It should be noted that patient motion can significantly limit NCEMRA images due to the resulting artifacts. Similar to CT angiography (as these studies are done in outpatient radiology centers and/or hospitals), there is a delay in obtaining the results of the study and prior authorization from insurers is often required. As with CT angiography, an asymmetric stenosis can cause issues with contrast image acquisition. Pros: Calcification does not limit image interpretation; excellent spatial resolution and anatomic definition; acquisition does not necessarily require contrast Cons: Patient discomfort due to claustrophobia; cost; delay in obtaining results; cannot use gadolinium with renal insufficiency; artifact associated with NCEMRA; limited contrast image acquisition with asymmetric stenosis Figure 8. Three-vessel runoff to the right foot. gadolinium contrast-enhanced MR angiography (CE- MRA). This study is similar to CT angiography in that CEMRA is performed using bolus contrast infusion with timing of acquisition of images. Non-contrast time of flight MR angiography (NCEMRA) uses the principles of blood Conventional Angiography Conventional angiography is the gold standard for peripheral arterial disease evaluation. At the time of angiography, both anatomic as well as hemodynamic information can be obtained. Anatomic information is gathered by injection of contrast with fluoroscopic imaging. Hemodynamic information is obtained by direct vascular pressure measurements to assist in determining stenosis severity and whether intervention is indicated. The primary advantage of this procedure is that both diagnosis and treatment can occur within the same procedure, limiting treatment time in addition to reducing contrast/ radiation exposure. The disadvantage of this procedure lies in the fact that it is invasive and needs to be performed in the hospital and/or outpatient lab setting. Similar to CT angiography, it exposes the patient to iodinated contrast and radiation. However, radiation exposure is often less with conventional angiography than CT angiography. Additionally, there is significant cost with the procedure over noninvasive imaging. Pros: Gold standard for peripheral arterial disease evaluation; diagnosis and therapy can occur simultaneously; less delay in time to treatment Cons: Invasive; cost; radiation exposure; iodinated contrast exposure 5

Returning to our case example, the CT angiogram demonstrated markedly different results than the conventional angiogram. This was expected, given the known vascular calcification, prior stent placement, and asymmetric stenosis that caused artefactual abnormalities. Additionally, CT angiography provided an unnecessary double dose of radiation and contrast as the patient s CLI warranted direct angiography with intervention. In evaluating patients with suspected or definite PAD, a fundamental understanding of the advantages and limitations of testing is crucial. Most importantly, the urgency of evaluation will determine the ideal imaging strategy. Reference 1. Alzamora MT, Fores R, Pera G, et al. Incidence of peripheral arterial disease in the ARTPER population cohort after 5 years of follow-up. BMC Cardiovascular Disorders. 2016;16:8. Additional References 2. Pollak AW, Norton PT, Kramer CM. Multimodality imaging of lower extremity peripheral arterial disease. Circ Cardiovasc Imaging. 2012;5(6):797-807. 3. Criqui MH, Aboyans V. Epidemiology of peripheral artery disease. Circ Res. 2015;116(9):1509-26. 4. Jens S. Imaging of critical limb ischemia. Uitgeverij BOXpress. The Netherlands. 2015. 5. Norgren L, Hiatt WR, Dormandy JA, et al. Inter-society consensus for the management of peripheral arterial disease. Int Angiol. 2007;26(2):81-157., LLC an HMP Communications Holdings Company Copyright 2016 All Rights Reserved. 70 East Swedesford Road. Suite 100 Malvern, PA 19355 Phone (610) 560-0500 Fax (610) 560-0501 6