Safety and Efficacy of Endovascular Therapy With a Simple Homemade Carbon Dioxide Delivery System in Patients With Ileofemoral Artery Diseases

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1 Circulation Journal Official Journal of the Japanese Circulation Society Advance Publication by J-STAGE Safety and Efficacy of Endovascular Therapy With a Simple Homemade Carbon Dioxide Delivery System in Patients With Ileofemoral Artery Diseases Daizo Kawasaki, MD, PhD; Kenichi Fujii, MD, PhD; Masashi Fukunaga, MD; Motomaru Masutani, MD, PhD; Aya Nakata; Tohru Masuyama, MD, PhD Background: Carbon dioxide (CO2) has been used as an arterial contrast agent for high-risk patients who were allergic to iodinated contrast material and for those with chronic kidney disease (CKD). The feasibility, safety, imaging quality and therapeutic role of CO2 angiography in the endovascular therapy (EVT) for patients with CKD was evaluated. Methods and Results: EVT was performed in 107 consecutive patients with iliofemoral artery disease (148 limbs; mean age, 73±9 years) who were admitted to our hospital from January 2010 to April Intravascular ultrasound (IVUS)-guided EVT with CO2 was applied for the treatment of 50 patients (70 limbs) with CKD (group 1). IVUSguided EVT with iodinated contrast media was applied for the treatment of 57 patients (78 limbs) without CKD (group 2). CO2 was injected by hand using a simple homemade delivery system. The overall technical success was 100% in both groups without any major complication. Preprocedure and postprocedure ankle-brachial indices significantly improved in the both groups (0.93±0.11 vs. 0.59±0.19, P<0.01; 0.95±0.13 vs. 0.62±0.22, P<0.01, respectively). All of the CO2 arteriograms were good or acceptable imaging quality if assessed by 2 independent observers. Conclusions: CO2 arteriograms, using an inexpensive simple homemade delivery system, are feasible and safe in patients with CKD in the evaluation and for EVT of iliofemoral artery disease. Key Words: Carbon dioxide angiography; Chronic kidney disease; Endovascular therapy The mortality of the chronic phase is high, although the indication of endovascular therapy (EVT) for iliofemoral artery disease is expanded and is also a favorable long-term patency. 1,2 Contrast-induced nephropathy (CIN) is one of the most important clinical complications associated with EVT, accounting for 10% of all causes of hospital-acquired renal failure. 3 Elderly patients presenting with peripheral artery disease (PAD) often have coexisting renal, cardiac, diabetic and other medical illnesses that further increase the risk of these complications. Thus, much of the risk associated with the management of PAD is due to the use of the iodinated contrast itself in many patients. In the 1970 s, Hawkins pioneered the intra-arterial use of carbon dioxide (CO2) gas for high-risk patients who were allergic to iodinated contrast material and for those with renal insufficiency. 4 Although there are some problems such as the complexity of delivery of the CO2 gas, insufficient filling and fragmentation of the arteries causing inadequate visualization, vapor lock phenomenon, the possibility of injecting excessive volumes and explosive delivery, and inadvertent injection of room air, these risks/limitations could be overcome by using an appropriate injection method of CO2 gas and using precautions; following this generally does not cause problems with imaging. As there is some evidence that CIN is related to the volume of iodinated contrast media used, 5 we might reduce the frequency of nephropathy by the usage of a CO2 arteriogram. Although there have been several studies reporting the safety and feasibility of CO2 angiography as a diagnostic tool of PAD, the possibility of CO2 angiography as a therapeutic tool of PAD has not been reported. The purpose of this study was to retrospectively evaluate the feasibility, safety, imaging quality and therapeutic role of a CO2 arteriogram using a simple homemade delivery system for the EVT of iliofemoral artery disease in patients with chronic kidney disease (CKD). Methods Patients and Lesions This study included 107 consecutive patients with iliofemoral Received November 29, 2011; revised manuscript received March 12, 2012; accepted March 13, 2012; released online April 14, 2012 Time for primary review: 54 days Cardiovascular Division, Department of Internal Medicine (D.K., K.F., M.F., T.M.), Division of Coronary Heart Disease, Department of Internal Medicine (M.M.), Division of Clinical Engineering (A.N.), Hyogo College of Medicine, Nishinomiya, Japan Mailing address: Tohru Masuyama, MD, Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya , Japan. masuyama@hyo-med.ac.jp ISSN doi: /circj.CJ All rights are reserved to the Japanese Circulation Society. For permissions, please cj@j-circ.or.jp

2 KAWASAKI D et al. Figure 1. A simple homemade delivery system used for carbon dioxide angiography used in the present study. (A) The gas was purged 3 4 times during collection to exclude room air contamination from the tube and the delivery syringe in the circuit filled at a stationary flow of 2 L/min (B D). After the gas from the tube into a delivery syringe was aspirated, we connected it to the sheath with a 3-way stopcock. Approximately 5 ml of CO2 gas in the nozzle of the syringe was promptly expelled to eliminate possible room air contamination from the 3-way stopcock of the sheath (E). Finally, we carefully injected the CO2 gas into the vessel from the sheath (F). artery disease who were admitted to our institution between January 2010 and April These patients underwent intravascular ultrasound (IVUS)-guided EVT for 148 de novo lesions in the iliac and/or femoral artery disease segment. IVUSguided EVT with CO2 was applied for the treatment of 50 patients (70 limbs) with CKD (group 1). IVUS-guided EVT with iodinated contrast media was applied for the treatment of 57 patients (78 limbs) without CKD (group 2). In this study, CKD was defined as <60 ml min m 2 the estimated glomerular filtration rate (egfr) according to the formula recommended by the Japanese Society of Nephrology. We excluded patients who received hemodyalysis, or who had multi-segment disease, infrapopliteal artery lesion and restenotic lesions. None of the patients had a history of allergy to iodinated contrast media. This study was approved by the institutional ethics committee, and written informed consent for the procedure was

3 Endovascular Therapy With Carbon Dioxide Angiography obtained from each patient. Fifty patients with CKD (group 1) were hydrated intravenously with isotonic 0.9% NaCl solution in case iodinated contrast media was used. An intravenous infusion of isotonic 0.9% NaCl at 1 ml kg 1 h 1 was started 12 h prior to the procedure and continued for up to 12 h post procedurally. In patients with heart failure, the volume of fluid was reduced to 50% of the calculated values. Conversely, 57 patients without CKD (group 2) were not hydrated. Aspirin and cilostazol or ticlopidine were started 48 h before the procedure and continued during the follow-up period in all patients. Preprocedure Evaluation in Patients With CKD Initially, we assessed the physiological function of the limbs with an ankle-brachial index (ABI) and duplex examination that included an assessment of the flow wave pattern and extent of occlusive disease in the iliac and/or femoral arterial segments. When abnormal physiological findings were observed, we identified the target lesion with the use of a duplex flowwave pattern and magnetic resonance angiography (MRA) without contrast media. The extent and distribution of calcification in the arterial wall was evaluated with the use of plane computed tomography (CT) because this information is very important and useful for placing the guidewire that crosses the occlusive lesions successfully. None of the patients in this series had a preprocedure examination using iodinated contrast media, such as CT angiography, MRA, and X-rays arteriography with catheters. Simple Homemade CO2 Delivery System The simple homemade CO2 delivery system consisted of a medical-grade CO2 gas cylinder with a regulator, a regular disposable sterile plastic tube with a bacteria removal filter, and a 3-way stopcock and delivery syringe of 50 ml (Figure 1A). The bacteria removal filter has pores of 200 μ in diameter for the removal of any particulate matter that might be present in the gas obtained from the gas cylinder. To fill the tube with CO2, the inlet tube was connected to the medical-grade CO2 gas cylinder. The outlet port of this tube was then connected to the 3-way stopcock. The gas was purged 3 4 times during collection to exclude room air contamination from the tube, and the delivery syringe in the circuit was filled with a stationary flow at 2 L/min (Figures 1B D). After we liberally aspirated 55 ml of gas from the tube into the delivery syringe, we connected it to the sheath with a 3-way stopcock. Approximately 5 ml of the CO2 gas in the nozzle of the syringe was promptly expelled to eliminate possible room air contamination from the 3-way stopcock of the sheath (Figure 1E). Finally, we injected CO2 gas carefully into the vessel from the sheath (Figure 1F). Technique of CO2 Injections Through a Sheath All CO2 injections were done by hand. In case an abdominal aorta injection was required, approximately 55 ml of CO2 was aspirated from the tube and 5 ml of the gas was expelled to eliminate room air contamination from the 3-way stopcock of the sheath. During the injection, the nozzle of the syringe was tilted downwards. The gas injection in the vessel leaves the gas of 5 cc in the injection syringe (Figure 1F). After the gas injection, the gas and blood was carefully aspirated into the sheath. Gas injections were spaced approximately 30 s apart. The total volume of CO2 that was used per procedure ranged from 50 to 600 ml (mean volume, 264±122 ml). Evaluation of CO2 Arteriograms Evaluation of CO2 arteriograms was conducted independently by 2 cardiologists who did not perform the procedure. The CO2 arteriogram images from each patient were given an overall subjective grade of good, acceptable or poor. It was considered a good grade when the anatomical details were shown as well as the iodinated contrast medium, DSA. An acceptable grade was given when there was some loss of anatomical details, which did not affect the procedure. And it was considered a poor grade when there was a significant loss of anatomical details, which affected the procedure. Complications Related to the CO2 Injection Heart and respiratory rates, oxygen saturation, electrocardiogram and blood pressure monitoring were performed for all patients during the procedure. Any specific complaints from the patient during the procedure and after the procedure were recorded. Treatment All cases were performed under local anesthesia. After sheath insertion, heparin of 5,000 Units was administered. A total of 148 lesions were treated with the guidance of IVUS. We have previously reported that IVUS-guided EVT for the iliac and/or femoropopliteal arteries is feasible and safe, minimizes contrast material, and has a high initial technical success rate. 6,7 In both groups, after the occlusion was crossed and recanalized by a guidewire, the diseased segment was then balloondilated. The balloon diameter and length were determined according to the geometry of the lesions measured by IVUS. When plaque dissections or recoils caused a stenosis of 30% or more, stents were implanted under IVUS guidance. In the iliac lesions, a balloon-expandable stent or a self-expandable stent was used if stent implantation was necessary. In contrast, only a self-expandable stent was used in the femoropopliteal lesions, if stent implantation was necessary. Postprocedure Evaluation and Follow up Arterial duplex scanning, ABI and serum concentration of creatinine were routinely examined before hospital discharge and after 1 month. Patients were advised to schedule followup visits in our outpatient office for clinical evaluation and arterial duplex scans, and ABIs within the first month after discharge and every 3 months thereafter. The procedure complications included: vessel perforation, clinically detectable lower extremity or visceral embolization, pseudoaneurysms, arterio-venous fistulas, and hematomas of the femoral puncture for in-hospital patients. The adverse events were defined as death, stroke, amputation, and target lesion revascularization. Statistical Analysis Statistical analysis was performed with StatView 5.0 (STAT- VIEW II, Abacus Concepatients, Berkeley, California). Results are expressed as mean ± SD. The unpaired Student s t-test was used to compare the values between the 2 groups. The differences in frequencies of sex, patient s risk factor and target lesion revascularization were analyzed by using the chi-square test. A P value of less than 0.05 was considered statistically significant. The inter-observer agreements were estimated based on Cohen s κ coefficient. Results Immediate Results Baseline clinical, lesion, and procedural characteristics are summarized in Tables 1 and 2. The egfr ranged from 5 to

4 KAWASAKI D et al. Table 1. Patients Characteristics Group 1 (n=50 ) Group 2 (n=57) Age (years) 74±10 73±8 Male (%) 91 68** Hypertension (%) 95 82* Diabetes mellitus (%) Dyslipidemia (%) Current smoker (%) egfr (ml min m 2 ) 25±7 69±15** Fontaine grade (1/2/3/4) (n) 0/41/5/4 0/53/3/1 Cilostazol use (%) Age is presented as mean ± SD. *P<0.05; **P<0.01. egfr, estimated glomerular filtration rate. 37 mg/dl (average, 25±7 ml min m 2 ) in patients from group 1. Iodinated contrast media was used during the procedure in only 3 cases from group 1. Iodinated contrast media was used to evaluate the infrapopliteal arteries in 2 patients, and to identify arterial perforation in the other patients (average volume 1.5±6.0 ml). Fortunately, CIN did not occur in any of these patients. The procedure time was shorter in group 1 than in group 2 in terms of the iliac lesions. In contrast, the procedure time was longer in group 1 than in group 2 in terms of the femoral lesions, indicating that the procedure time depends on a number of chronic total occlusions (Table 2). Representative Cases and Imaging Quality of CO2 DSA Figures 2A and B shows representative CO2 arteriograms before and after EVT in a 71-year-old male with intermittent claudication in the both calves for 3 months. The diagnostic CO2 arteriogram shows stenosis of the terminal abdominal aorta before treatment (Figure 2A). After the guidewire crossing from the common femoral artery to the abdominal aorta, the lesion was dilated with a 7.0 mm balloon and then 2 lots of mm Cordis SMART TM nitinol self-expandable stents (Cordis Corporation, Warren, NJ, USA) were implanted from the abdominal aorta to both common iliac arteries under IVUS guidance. Figure 2B shows the final CO2 arteriogram. Figures 2C and D shows representative CO2 arteriograms before and after EVT in a 62-year-old male with intermittent claudication in the right calf for 9 months. A diagnostic CO2 arteriogram shows total occlusion from the ostium to the mid-portion of the right superficial femoral artery with good collaterals from the deep femoral artery before treatment (Figure 2C). After the guidewire crossing, in the distal vessel segment of the superficial femoral artery, the lesion was dilated with a 4.0 mm balloon and then a 6.0 mm Cordis SMART TM nitinol self-expandable stent (Cordis Corporation, Warren, NJ, USA) was implanted under IVUS guidance. Figure 2D shows the final CO2 arteriogram. Table 3 shows the image value of CO2 arteriograms. All of the CO2 arteriograms were of good or acceptable imaging quality. In our study, the kappa value was 0.914, suggesting a high interobserver agreement in the imaging quality of the CO2 arteriograms. Problems and Complications Related to the CO2 Injection We evaluated the incidence of various complications related to the CO2 injection. Among the total of 70 cases, 6 cases experienced transient leg pain during the CO2 injection into the femoral artery and/or infrapopliteal arteries, and 1 case experienced transient abdominal pain during the CO2 injection into Table 2. Lesion and Procedure Characteristics Group 1 Group 2 Iliac artery (n) n TASC II classification (A/B/C/D) 13/10/3/3 14/11/2/6 Chronic total occlusion 6 11 Stenotic lesion Lesion length (mm) 48±27 61±34 Stent number (n) 1.0± ±0.4 Stent length (mm) 67±28 82±36 Stent diameter (mm) 8.4± ±1.2 Technical success rate (%) Procedure time (min) 31±17 45±24* Complication during procedure (n) 0 0 CO2 injection number (n) 4.0±3.0 0** CO2 injection Volume (ml) 200±148 0** Contrast media volume (cc) 0 53±24** Femoral artery (n) n TASC II classification (A/B/C/D) 10/6/16/9 9/13/15/8 Chronic total occlusion Stenotic lesion Lesion length (mm) 146±69 146±77 Stent number (n) 1.9± ±0.9 Stent length (mm) 168±83 164±84 Stent diameter (mm) 6.3± ±0.4 Technical success rate (%) Procedure time (min) 61±20 53±18* Complication during procedure (n) 1 0 CO2 injection number (n) 7.4±2.0 0** CO2 injection volume (ml) 306±80 0** Contrast media volume (cc) 1.5±6.0 49±15** Values are given as a number. Continuous valuables are presented as mean ± SD. *P<0.05; **P<0.01. TASC, Trans Atlantic Inter-Society Consensus; CO2, carbon dioxide. the abdominal artery. However, our procedure was not affected by these unfavorable symptoms. No major complications occurred in our study, which required active treatment. Procedure Complications and Adverse Events in Hospital and During Follow up We experienced vessel perforation by the wire with a superficial femoral artery occlusion in 1 case of group 1, and this was confirmed by a CO2 arteriogram and the iodinated contrast medium. After repairing the hemorrhage, we successfully finished the procedure with a stent implantation (Table 2). Wire and catheter manipulation in the aorta and its branches did not cause clinically detectable lower extremity or visceral embolization in either group. Pseudoaneurysms, arterio-venous fistulas, or hematomas did not occur as a result of the femoral puncture. The mean duration of the follow up in these patients was 11.1±5.7 months (range, 3 18 months). We evaluated the adverse events for patients in-hospital and during follow-up periods. A patient in group 2 died because of esophageal cancer during the follow-up periods. There were no postprocedural strokes or amputations from either group. Five cases in each group received target lesion revascularization for re-stenosis with recurrent intermittent claudication during the fol-

5 Endovascular Therapy With Carbon Dioxide Angiography Figure 2. A diagnostic CO2 arteriogram before treatment shows stenosis of the terminal abdominal aorta (A). After the guidewire crossed from both the common femoral artery to the abdominal aorta, the lesion was dilated with a 7.0 mm balloon and then 2 lots of mm the Cordis SMART TM nitinol self-expandable stents (Cordis Corporation, Warren, NJ, USA) were implanted from the abdominal aorta to both common iliac arteries under IVUS guidance. (B) The final CO2 arteriogram. A diagnostic CO2 arteriogram before treatment shows total occlusion from the ostium to the mid-portion of the right superficial femoral artery with good collaterals from the deep femoral artery. (C) After the guidewire crossed the distal vessel segment of the superficial femoral artery, the lesion was dilated with a 4.0 mm balloon and then a 6.0 mm Cordis SMART TM nitinol self-expandable stent (Cordis Corporation, Warren, NJ, USA) was implanted under IVUS guidance. (D) The final CO2 arteriogram. Table 3. Image Value of Carbon Dioxide Digital Subtraction Image value (n) Observer 1 Observer 2 Iliac artery n 29 Good 6 5 Acceptable Poor 0 0 Femoral artery n 41 Good Acceptable Poor 0 0 Table 4. Change in Ankle Brachial Index and Serum Creatinine Concentration Ankle brachial index Group 1 Group 2 Before 0.59± ±0.22 After 0.93±0.11** 0.95±0.13** Serum creatinine concentration Before 2.19± ± days after the procedure 2.20± ± month after the procedure 2.06± ±0.16 Data are presented as mean ± SD. **P<0.01 (vs. before treatment).

6 KAWASAKI D et al. low-up periods. Changes in ABIs at Preprocedure and Postprocedure Table 4 shows the changes in ABI from preprocedure to postprocedure. The mean ABI significantly increased in both groups immediately after the EVTs (0.93±0.11 vs. 0.59±0.19, P<0.01, and 0.95±0.13 vs. 0.62±0.22, P<0.01, respectively). Changes in Serum Creatinine Concentration From Preprocedure to Postprocedure and 1 Month After Treatment Table 4 shows the serum creatinine concentration before and after treatment. The mean serum creatinine levels at 2 days and 1 month after the procedure did not differ from that at preprocedure in both groups (group 1: 2.20±1.13, 2.06±1.01 vs. 2.19±1.05 mg/dl; group 2: 0.82±0.19, 0.82±0.16 vs. 0.81± 0.18 mg/dl, respectively). None of the patients required hemodialysis after the procedure because of CIN or cholesterol embolization. Discussion CO2 arteriograms are particularly advantageous for patients at risk of CIN and allergic reactions against iodinated contrast media. The main findings of this study may be summarized as follows: (1) this new simple CO2 delivery system is easy to assemble, quick to learn, and requires only a few steps; (2) image quality of CO2 arteriograms is satisfactory enough in the area of the iliofemoral artery; and (3) IVUS-guided EVT with a CO2 arteriogram, as well as those of iodinated contrast media, seems to be safe and effective. Application of CO2 Angiography CO2 angiography should be considered if the patient has the following background: (1) when a patient has a risk of CIN; and (2) when a patient has a history of adverse reactions to contrast media. In this study, none of the patients had an iodine contrast allergy. Gadolinium has a different chemical structure with no cross reactivity with iodine-based contrast media in patients with an iodine allergy. Although gadolinium has been used in lower-limb arteriography with satisfactory results, there has been an increase in the recent reports of nephrogenic systemic fibrosis in patients with CKD who have been exposed to gadolinium. 8 This fact strongly emphasizes the advantage of CO2 treatment in patients with CKD. Safety of the Simple Homemade Carbon Dioxide Delivery System CO2 is a safe angiographic contrast medium. It is non-toxic, non-allergic, inexpensive, compressible, invisible, heavier than air, odorless, and exhibits extreme diffusion properties. The CO2 gas does not cause any changes in blood osmolarity, blood ph and blood gas values. 9 To confirm the safety of our delivery system, we measured the acidity (ph) and the levels of oxygen and CO2 in the artery from the sheath before and after the procedure in the first 10 cases. No parameter changed after the procedure. Since 1971, Hawkins has used multiple hand-delivery systems including multiple stopcocks and manifolds and has developed small dedicated hand-held and 5 different computer-controlled dedicated injectors. 4 In 1995, Hawkins et al also introduced a plastic bag delivery system, which applied the principles learned during the development of the dedicated injector. 10 This system has effectively eliminated the possibility of injecting excessive volumes and has reduced explosive delivery. The previously published delivery system has been also modified to reduce these problems. 11,12 Madhusudhan et al reported the safety of the CO2 angiography using a homemade CO2 delivery system that consisted of medical-grade CO2, a laparoflator, a disposable transfer bag, tubing with a filter, a 3-way tap, and a delivery syringe. Because the bag was used to transport the gas from the operating room to the DSA suite in this system, the procedures for preparing the system was complicated. 13 Unfortunately, the published CO2 delivery systems have been used only by a limited number of physicians and operators because of the complexity of the delivery system. Our delivery system is simpler and more user-friendly than the previously described published systems. The components of the system are easily obtainable in any hospital setup and are inexpensive. Because our delivery system does not require any complicated procedure for preparing the system, it does not consume time. And, this delivery system does not have the danger of explosive delivery because it is not a closed circuit. We performed a controlled injection of the CO2 gas by hand. The hand delivery injection of CO2 is fraught with several potential risks such as the delivery of unknown and possibly excessive volumes, explosive delivery and air contamination. Small contamination with room air, if present, is expected to be negligible. Dissolved CO2 should be expired through the lungs before reaching the coronary or cerebral circulation in a 1-pass fashion, eliminating the likelihood of a clinically significant gas embolism. In fact, we have not experienced any complication related to air contamination or embolism in our study. Six (14.6%) patients complained of transient lower limb pain during injection of the CO2 gas from the common femoral artery. Another patient (3%) experienced of transient abdominal pain during injection of the CO2 gas from the abdominal aorta. However, no major complications occurred in our study that required active treatment. Madhusudhan et al experienced 1 (4.8%) patient who complained of severe pain and 6 (28.6%) patients who complained of mild pain during the CO2 injection. 13 It has been reported that pain led to the discontinuation of 18% of examinations when high volumes and flow rates were used. 14 In practice, warning the patient what to expect, giving a test injection, and reducing volume and flow rates minimizes the side effects and improves tolerance. Thus, our new simple delivery system is safe, easy to assemble, fast to learn, and requires only a few steps. Imaging Quality of Carbon Dioxide Arteriograms Madhusudhan et al compared the image quality of CO2 arteriograms with the corresponding images of iodinated contrast media arteriograms in 27 limbs from 21 patients. Arteries from the aortic bifurcation to the ankle were independently assessed by 2 radiologists. It provides adequate imaging of the arteries of lower extremities, except for infrapopliteal segments. 13 Rolland et al reported that the imaging quality of CO2 arteriograms was comparable to the iodinated contrast media arteriograms from the pelvis in 93% and at the thigh in 74% of the 120 arteries studied. 15 To obtain fine images of CO2 arteriograms, we have to kept to a minimum all motion during image acquisition. We also minimized bowel peristalsis by using IV glucagon. In this study, all of the CO2 arteriograms taken by 2 independent observers were of good or acceptable quality. We used a lower rate and smaller volume compared to previous studies to minimize leg pain during CO2 injection. 16 As a cause of deterioration of image quality of the CO2 arteriogram, there is fragmentation of the CO2 gas column, especially in the femoral and infrapopliteal arteries. The fragmentation is due to a trapping phenomenon and incomplete filling to the artery.

7 Endovascular Therapy With Carbon Dioxide Angiography Kerns and Hawkins suggested that the catheter be placed as close as possible to the lesion to improve the filling of the vessel with the gas. They also reported that the use of vasodilators improved distal filling. 16 Safety of IVUS-Guided Endovascular Therapy Without Iodinated Contrast Media IVUS-guided EVT with a CO2 arteriogram seemed to be as safe and effective as a conventional iodinated contrast media angiography. As previously reported by our group, 6,7 this IVUS system can be used not only to identify the exact location and severity of the occlusive disease process, but also to precisely measure the extent of the lesion. In the current study, the procedures were performed by 2 attending interventional cardiologists. A majority of the procedures were performed by the first author (D.K.). There was no difference in success rate, procedure time, fluoroscopic time, and radiation exposure dose between the measurements taken by the 2 interventional cardiologists. However, there might be an inverse relationship between physician caseload and procedure-related complication, procedure time, and fluoroscopic time. There was no difference in procedure time, fluoroscopic time and radiation exposure dose between the IVUS-guided EVT with a CO2 arteriogram and conventional IVUS-guided EVT with contrast media (data not shown). IVUS might allow us to assess the exact extent of the atherosclerotic plaques to be treated with stents. Study Limitations There were some limitations to this study. First, this study was a single-center study with a relatively low study population. Second, we should have compared the CO2 angiography and the iodinated contrast media in patients with comparable renal insufficiency in order to clearly address the issue of renal insufficiency, but we did not have the data of EVT using the iodinated contrast media in patients with renal insufficiency. 7 Third, some potential complications such as distal embolization, air embolization, arterial spasm, dissection and wire perforation might have been overlooked in some patients. These complications, especially in patients with critical limb ischemia, might lead to poor blood flow. In our opinion, complete duplex scanning is mandatory to assess the adequacy of the technique and to document the expected hemodynamic improvement. If there is an inadequate image of the peripheral artery despite selective injection, it should be supplemented with some amount of iodinated contrast media for better visualization of the peripheral artery in question. Further studies are required to reconfirm the effectiveness of IVUS-guided EVT with a small amount of iodinated contrast media and CO2 angiography. Conclusions CO2 application, using an inexpensive simple homemade CO2 delivery system, is a feasible and safe option for patients with CKD in the evaluation and for the EVT of iliofemoral artery disease. We suggest that a CO2 arteriogram can be used as an initial contrast agent for the evaluation of iliofemoral artery disease in patients with CKD. References 1. Soga Y, Yokoi H, Urakawa T, Tosaka A, Iwabuchi M, Nobuyoshi M. Long-term clinical outcome after endovascular treatment in patients with intermittent claudication due to iliofemoral artery disease. Circ J 2010; 74: Suzuki K, Iida O, Soga Y, Hirano K, Inoue N, Uematsu M, et al. Long-term results of the S.M.A.R.T. Control TM stent for superficial femoral artery lesions, J-SMART registry. Circ J 2011; 75: Tepel M, Aspelin P, Lameire N. 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Comparison of intra-arterial digital subtraction angiography using carbon dioxide by home made delivery system and conventional iodinated contrast media in the evaluation of peripheral arterial occlusive disease of the lower limbs. J Med Imaging Radiat Oncol 2009; 53: Díaz LP, Pabón IP, García JA, de la Cal López MA. Assessment of CO2 arteriography in arterial occlusive disease of the lower extremities. J Vasc Interv Radiol 2000; 11: Rolland Y, Duvauferrier R, Lucas A, Gourlay C, Morcet N, Rambeau M, et al. Lower limb angiography: A prospective study comparing carbon dioxide with iodinated contrast material in 30 patients. Am J Roentgenol 1998; 171: Kerns SR, Hawkins IF Jr. Carbon dioxide digital subtraction angiography: Expanding applications and technical evolution. Am J Roentgenol 1995; 164: