Abstract Endovascular intervention is an appealing revascularization strategy for iliac artery disease. Atherectomy of the iliac artery is uncommon due to the risk of life-threatening perforation but may be necessary if the iliac lesion is heavily calcified, preventing stent delivery or optimal expansion. We assessed the feasibility and safety of orbital atherectomy for the treatment of iliac artery disease. Demographic data, lesion characteristics, and procedure outcomes for the CONFIRM patients with at least one iliac artery lesion treated with orbital atherectomy ( n = 62 patients; n = 68 lesions) were compared to patients with at least one superficial femoral artery (SFA) lesion treated with orbital atherectomy ( n = 1570 patients; n = 1809 lesions). The procedural complication rate, defined as the composite of flow limiting dissection, perforation, slow flow, vessel closure, spasm, embolism, or thrombosis, was compared in iliac lesions versus SFA lesions. The iliac artery group had more patients with diabetes, shorter lesions, and more severely calcified lesions. The orbital atherectomy run time was significantly shorter in the iliac artery group. Additionally, in the iliac group there was one reported perforation and one reported vessel closure; the rates of slow flow, spasm, embolism, thrombus, and flow limiting dissection were 0%. The overall procedural complication rate was significantly lower in the iliac group (2.9% vs. 11.2%, p = 0.03). Orbital atherectomy of the iliac artery is feasible with few reported angiographic complications and compared favorably with the SFA group. Orbital atherectomy may be considered to facilitate the delivery and expansion of a balloon or stent if the iliac artery is calcified. 1 Introduction Endovascular intervention is a common treatment strategy for iliac artery disease given that it is less invasive than bypass surgery, does not require general anesthesia, has a high rate of technical success, and provides durable patency. The 2016 AHA/ACC Guidelines on the Management of Patients with Lower Extremity Peripheral Artery Disease (PAD) state that endovascular procedures are effective as a revascularization strategy for patients with lifestyle-limiting claudication and hemodynamically significant aortoiliac occlusive disease. The standard of care for the endovascular treatment of iliac artery disease is stenting. However, the presence of calcification may preclude the delivery and optimal expansion of the stent, leading to restenosis, recurrence of ischemia, and the need for repeat revascularization. Modification of calcified plaque with atherectomy may facilitate stent delivery and expansion. However, treatment of the iliac artery is of higher risk given the potential for a life-threatening retroperitoneal bleed if a perforation occurs. Data are limited on the feasibility and safety of atherectomy of the iliac artery. We assessed the feasibility and safety of orbital atherectomy treatment for iliac artery lesions. 2 Methods 2.1 Study design The CONFIRM I, II, and III registries prospectively enrolled 3135 patients with 4766 lesions at over 200 US centers who were treated with orbital atherectomy from October 2009 through June 2011. There were no study inclusion or exclusion criteria; however, the orbital atherectomy system was used in accordance with its approved indication. Baseline patient demographic data, lesion characteristics, and procedure outcomes for CONFIRM patients with at least one iliac lesion ( n = 62 patients; n = 68 lesions) were compared to patients with at least one superficial femoral artery (SFA) lesion ( n = 1570 patients; n = 1809 lesions). Patients with both an iliac and SFA lesion were not included in the analysis. The procedural complication rate, defined as the composite of flow limiting dissection, perforation, slow flow, vessel closure, spasm, embolism, or thrombus formation, was compared in iliac lesions versus SFA lesions treated with orbital atherectomy. All procedural and outcome data was site-reported; there was no core lab adjudication of CONFIRM data. 2.2 Device description Three device iterations of the orbital atherectomy system (Cardiovascular Systems, Inc., St. Paul, Minnesota) with crown sizes ranging from 1.25 mm to 2.25 mm were evaluated in the registry series: CONFIRM I registry evaluated the Diamondback360°; CONFIRM II evaluated the Predator360°; and CONFIRM III evaluated the Diamondback360°, Predator360°, and Stealth360°. The orbital atherectomy system was previously described. 2.3 Statistical methods Categorical variables are reported as frequency counts and percentages. Continuous variables are presented as mean ± standard deviation, while minimum and maximum values are reported to indicate data ranges. Relationships between various patient or lesion characteristics and patient outcomes were analyzed by cross-tab analysis. Chi-squared (χ 2 ) p -values are reported. p -Values < 0.05 were considered statistically significant. Statistical analyses were done using SAS version 9.3. 3 Results 3.1 Patient and lesion characteristics As shown in Table 1 , the iliac artery and SFA groups were similar in terms of baseline demographics, however the iliac artery group had a lower prevalence of diabetes mellitus (37.7% vs. 54.3%, p = 0.01). There was a higher percentage of lesions with severe calcification, defined as calcium > 75% of the lesion as assessed by the Investigator, in the iliac artery group (65.7% vs. 42.3%, p < 0.001) and compared to the SFA group, the target lesions were shorter in the iliac artery group (47.2 ± 37.6 mm vs. 85.7 ± 81.1 mm, p < 0.001) ( Table 2 ). Table 1 Patient demographics. Data are presented as number (%) or mean ± standard deviation. SFA = superficial femoral artery. Table 2 Lesion characteristics. Data are presented as number (%) or mean ± standard deviation. SFA = superficial femoral artery. 3.2 Procedural characteristics and adjunctive therapy Patients in the SFA group had significantly more lesions treated compared to patients in the iliac artery group (1.62 ± 0.85 vs. 1.31 ± 0.53, p = 0.004). Procedural data by lesion is presented in Table 3 . The 2.25 mm crown was used more frequently for the treatment of iliac artery lesions (47.8% vs. 16.2%, p < 0.001) and the total orbital atherectomy run time was significantly shorter in the iliac artery group (104 ± 55 s vs. 127 ± 80 s, p = 0.02). Compared to the SFA group, stents were more commonly used as adjunctive therapy after orbital atherectomy in the iliac artery group (35.3% vs. 9.8%, p < 0.001). Table 3 Procedural data by lesion. Data are presented as number (%) or mean ± standard deviation. SFA = superficial femoral artery. 3.3 Procedural complications The procedural complication rate was low in both groups, however it was significantly lower in the iliac artery group (2.9% vs. 11.2%, p = 0.03) ( Table 4 ). The rates of perforation and vessel closure in the iliac artery group were low (both 1%). The one vessel perforation in the iliac artery group was treated with a Viabahn stent. No iliac artery patients experienced slow flow, spasm, embolism, or thrombus. Table 4 Angiographic complications by lesion. Data are presented as number (%). SFA = superficial femoral artery. 4 Discussion In this retrospective analysis of the CONFIRM registries, orbital atherectomy of the iliac artery was feasible and resulted in similar low rates of angiographic complications when compared to SFA lesions treated with orbital atherectomy. Iliac artery stenting provides comparable patency compared with aorto-femoral bypass surgery with a lower risk of infection and bleeding that is associated with extensive abdominal incisions. The iliac artery is particularly amenable to endovascular treatment due to its large diameter and high flow rates. However, chronic calcified lesions can lead to increased procedural complications . Various treatment modalities have been investigated for modification of calcified peripheral arterial lesions including filter-protected atherectomy, rotational atherectomy, and laser atherectomy, without definitive evidence or guidelines to support the use of these tools . Data on atherectomy of the iliac artery are limited. However, modification of the calcified plaque in the iliac artery may be necessary to facilitate successful delivery and expansion of the stent. Although multiple generations of rotational atherectomy devices have been shown to safely treat femoro-popliteal disease, data are lacking for their use in the iliac artery . As the iliac artery account for over one-quarter of all cases of symptomatic peripheral arterial disease, there is a high demand for the implementation of effective revascularization techniques, especially in occluded calcified vessels . There is a lack of consensus regarding the use of atherectomy for iliac artery disease. If a standard balloon cannot traverse the lesion or fully expand in the heavily calcified plaque in the iliac artery, a scoring balloon may be used. However, a literature review did not reveal any data with the technology in this lesion subset. Another consideration is aorto-femoral bypass surgery, especially if the non-dilatable lesion requires high-pressure balloon inflations to adequately dilate the lesion and expand the stent. However, aggressive dilatation could lead to a catastrophic complication like iliac artery rupture, necessitating life-threatening treatment. The higher risk of perforation with atherectomy is one reason why it is avoided in iliac artery disease. Such complication can lead to a life-threatening retroperitoneal bleeding requiring emergent surgical repair if it is not successfully treated with a covered stent. A literature review resulted in no studies with orbital atherectomy of the iliac artery. The CONFIRM registries reported the feasibility and safety of orbital atherectomy for the treatment of PAD. This sub-analysis of patients with iliac artery disease who underwent orbital atherectomy in the CONFIRM registries provides insight into a patient population that is lacking in data. In the iliac artery group, the rate of perforation was 1.5%, as was the rate for vessel closure. No patients in the iliac artery group experienced flow limiting dissection, slow flow, spasm, embolism, or thrombus. 4.1 Limitations This was a single-arm registry of PAD patients undergoing orbital atherectomy, which may lead to observational bias. There were no comparisons with aorto-femoral bypass surgery or other atherectomy devices (directional, rotational, and laser atherectomy). Angiographic outcomes were not adjudicated by an angiographic core lab, which introduces the potential for subjective bias. The data on clinical outcomes, including mortality, restenosis, and amputation, were not reported. Significant differences in patient, lesion, and procedural characteristics as well as adjunctive therapy between the two groups may also have resulted in bias. 5 Conclusion Severely calcific iliac artery increases the technical complexity of stenting. Our sub-analysis of the CONFIRM registries demonstrated the feasibility and safety of orbital atherectomy for the treatment of calcified iliac artery disease. The rates of perforation and vessel closure were low, and there were no cases of flow limiting dissection, slow flow, spasm, embolism, and thrombus. A randomized trial with long-term follow-up is needed to determine the ideal revascularization strategy for patients with calcified iliac artery disease.