CASE REPORT

Endovascular Therapy Using Diluted Contrast Medium for Critical Limb Ischemia in a Patient with Chronic Kidney Disease

Naoki Hayakawa,1 MD, Satoshi Kodera,1,2 MD, Noriyoshi Ohki,3, Syunichi Kushida,1 MD, Hiroyuki Morita,2 MD, Junji Kanda,1 MD and Issei Komuro,2 MD

Summary A high percentage of patients with critical limb ischemia have concurrent chronic kidney disease (CKD). However, endovascular therapy (EVT) can be problematic in CKD patients. Thus, we developed a method of EVT using digital subtraction (DSA) with diluted contrast medium (low-concentration DSA), wherein DSA parameters were adjusted for diluted contrast angiography (1:10 dilution). Herein, we report the case of an 88-year-old woman with a foot wound and severe CKD. Her estimated glomerular filtration rate was 7.9 mL/minute/1.73 m2. Therefore, EVT was performed with low-concentration DSA. Control angiography re- vealed total occlusion of the anterotibial and posterotibial arteries as well as severe stenosis of the peroneal ar- tery. EVT with ballooning of the below-the-knee (BTK) lesions resulted in sufficient flow to the wound. Angi- ographic images of sufficient quality and visible wound blush were obtained with 1:10 diluted contrast medium. Because only 20 mL of contrast medium was required, renal function was preserved. EVT using DSA with di- luted contrast medium was shown to be an effective BTK intervention in this CKD patient. (Int Heart J 2019; 60: 226-230) Key words: Contrast-induced nephropathy, Below-the-knee intervention, Digital subtraction angiography

high percentage of patients with critical limb 1773.0 pg/mL, while the patient’s ankle-brachial index ischemia have concurrent chronic kidney disease was 0.58 on the right side and 0.79 on the left. Noncon- A (CKD). However, endovascular therapy (EVT) trast magnetic resonance angiography revealed total occlu- can be problematic in CKD patients because the use of a sion from the right common iliac artery to the external large volume of iodinated contrast medium is associated iliac artery and left below-the-knee (BTK) lesions. How- with an increased risk of contrast-induced nephropathy ever, details of BTK lesions could not be discerned be- (CIN).1) We developed a method of EVT using digital cause of poor image quality. subtraction angiography (DSA) with diluted contrast me- We first attempted to treat the chronic total occlusion dium (low-concentration DSA). Herein, we report a case of the right iliac artery. We deployed 2 SMARTⓇ in which EVT with low-concentration DSA achieved re- (8.0/60 mm, 7.0/40 mm; Cardinal Health Japan, Tokyo, vascularization while preserving the patient’s renal func- Japan) from the distal external iliac artery to the proximal tion. common iliac artery with an (IVUS)-guided approach using 7 mL of contrast medium. The patient’s right ankle-brachial index increased to 1.28 Case Report after this treatment. An 88-year-old woman with progressive rest pain, ul- Two weeks after the first session, EVT was per- ceration, and necrosis of both lower limbs (Figure 1) was formed for the BTK lesions on the left side. Due to the referred to our institution for . At presen- difficulty of applying only the IVUS-guided approach to tation, the patient had hypertension, atrial fibrillation, BTK intervention, we performed EVT using an adjusted chronic heart failure, and CKD. Her height was 150 cm DSA program with diluted contrast medium to preserve and her weight was 40.4 kg. Initial serum urea nitrogen renal function. Angiography was performed with an Allura was 53 mg/dL and creatinine was 4.36 mg/dL. The pa- Xper FD10 machine (Philips, Amsterdam, The Nether- tient’s estimated glomerular filtration rate (eGFR) was lands). We adjusted the DSA parameters and found that only 7.9 mL/minute/1.73 m2. Her left ventricular ejection we could obtain acceptable images with a 1:10 dilution of fraction was approximately 40%, with diffuse hypokinesis contrast medium. The specialized parameters greatly in- of the heart wall. Her serum brain natriuretic peptide was creased the sensitivity of the angiographic images and en-

From the 1Department of Cardiovascular Medicine, Asahi General Hospital, Chiba, Japan, 2Department of Cardiovascular Medicine, The University of Tokyo Hospital, Tokyo, Japan and 3Department of Radiology, Asahi General Hospital, Chiba, Japan. Address for correspondence: Naoki Hayakawa, MD, Department of Cardiovascular Medicine, Asahi General Hospital, I-1326 Asahi, Chiba 289-2511, Japan. E-mail: [email protected] Received for publication February 26, 2018. Revised and accepted April 23, 2018. Released in advance online on J-STAGE November 20, 2018. doi: 10.1536/ihj.18-125 All rights reserved by the International Heart Journal Association. 226 IntHeartJ January 2019 ENDOVASCULAR THERAPY USING DILUTED CONTRAST MEDIUM 227

Figure 1. Lower limbs of 88-year-old woman with chronic kidney disease. Both lower limbs show ulceration and necrosis.

Table. Comparison Between Standard uct was 6.9 Gy cm2. Total procedure time was 44 minutes DSA and LC-DSA and fluoroscopic time was 21.1 minutes. The patient’s re- Standard DSA LC-DSA nal function was preserved (preprocedure eGFR, 7.9 mL/ minute/1.73 m2; postprocedure eGFR, 12.3 mL/minute/ Sensitivity normal high 2 Edge kernel small large 1.73 m ) and she has not required in the 2 Contrast 1.0 4.5 years since treatment. The patient’s skin perfusion pres- Edge gain 3 1 sure in the left dorsal region increased from 43 mmHg to DSA indicates digital subtraction angiogra- 123 mmHg at approximately 1 week after the procedure. phy; and LC, low concentration. Following this intervention, minor amputation was per- formed by a plastic surgeon. The patient’s wound healed completely without worsening of renal function. hanced the contrast, resulting in high resolution. The pa- rameters also lowered the edge strength caused by in- Discussion creased noise (Table). We used a preset diluted contrast solution containing 10 mL of iopamidol 300 mg/mL con- EVT can be problematic in CKD patients. The proce- trast medium (BYSTAGE 300Ⓡ; Teva Takeda Pharma Ltd., dure is associated with complications such as CIN,1) espe- Aichi, Japan) and 90 mL of 5% glucose. The contrast me- cially in patients with critical limb ischemia who require dium was the same as that used in standard EVT. We repeat interventions to achieve complete wound healing manually injected approximately 5 to 10 mL of the di- because of the high rate of restenosis in BTK lesions.2,3) luted contrast medium per angiogram through the guiding The large volume of iodinated contrast medium often re- catheter, which was positioned in the proximal popliteal quired in conventional EVT is associated with the risk of artery. Control angiography with low-concentration DSA CIN.4) revealed total occlusion of the proximal anterotibial artery Various methods for preventing CIN have been re- and posterotibial artery, as well as severe stenosis of the ported, including hydration, hemofiltration, intravenous distal peroneal artery (Figure 2). The main vessels and administration of iloprost, and the use of ascorbic acid, ni- small collaterals were clearly identified (Figure 2). The corandil, or N-acetylcysteine.5-14) However, there is pres- patient reported no pain caused by diluted contrast injec- ently no gold standard method and CIN occurs in ap- tion. We passed the chronic total occlusion in the an- proximately 5%-18.5% of patients, even when preventive terotibial artery using a GradiusⓇ wire (Asahi Intec Co., methods are applied. The most effective method to pre- Aichi, Japan) and a ProminentⓇ microcatheter (Tokai vent CIN is contrast volume reduction15). However, despite Medical Co., Aichi, Japan) using low-concentration DSA- the dangers, many previous studies have used over 100 guided antegrade wiring. Additionally, we used a Cheva- mL of iodinated contrast medium, except when perform- lier floppyⓇ wire (Cardinal Health Japan, Tokyo, Japan) in ing carbon dioxide .5-14) the peroneal artery. After ballooning both lesions, the final EVT can be performed effectively with carbon diox- angiography showed acceptable flow to the left leg and ide angioplasty in CKD patients.16,17) However, this method the wound (Figure 3). We identified the main vessels and is associated with severe complications and poor image small branches and confirmed wound blush (Figure 3E). quality.18) Carbon dioxide angiography results in poor im- The total volume of contrast medium used was 20 mL, aging of BTK lesions because of gas bubbles. Moreover, which was markedly less than that used in the conven- patients often experience severe pain that may cause them tional procedure, which usually requires approximately to move their legs during the procedure. The quality of 100 ml or more of contrast medium. The dose area prod- DSA image tends to be degraded by this lower limb IntHeartJ 228 HAYAKAWA, ET AL January 2019

Figure 2. Control angiography. The main vessels and some branches are identified with low-concentration digital subtraction angiogra- phy. A: Control angiography from the diagnostic catheter located in the popliteal artery reveals total occlusion of the proximal anterotibial artery (ATA, arrow) and posterotibial artery (PTA, arrow). The peroneal artery is patent (PA, arrow). B: The black arrow indicates severe stenosis of the distal peroneal artery. C: Distal portion of below-the-knee artery. There are collaterals distal to the PTA (Collateral, arrow) D: Vessels below the ankle are readily identifiable. ATA indicates anterotibial artery; PA, peroneal artery; and PTA, posterotibial artery.

Figure 3. Final angiography. A: Final angiography from the guiding catheter located in the popliteal artery shows acceptable antegrade flow from the anterotibial artery to the dorsalis pedis artery. B-D: Vessels and collateral channels are readily identified. E: Wound blush is also identified (wound blush, arrow). DPA indi- cates dorsal pedis artery. IntHeartJ January 2019 ENDOVASCULAR THERAPY USING DILUTED CONTRAST MEDIUM 229 movement. tory, adjustment of the location of the angiogram or the The IVUS-guided approach effectively reduces the concentration of contrast medium is necessary. Third, this amount of contrast medium required.19,20) However, it is method cannot be used in patients with an allergy to con- difficult to determine the degree of blood flow as well as trast agent. the number of branch vessels and collaterals when using IVUS. Furthermore, IVUS is difficult if the IVUS catheter Conclusions cannot pass BTK lesions. To resolve the problems associated with IVUS, we We successfully performed EVT for BTK lesions in developed a DSA protocol with specialized diluted con- a CKD patient using DSA with diluted contrast medium. trast medium. Previous studies have reported computed to- We obtained clear angiographic images of the BTK le- mography angiography using diluted contrast at a dilution sions using a very small volume of iodinated contrast me- ratio of roughly 1:3 to 1:4.21) However, to our knowledge, dium. EVT using low-concentration DSA was a very ef- there are no reports of intra-arterial DSA with diluted fective BTK intervention that preserved renal function in contrast medium. DSA with diluted contrast medium was this CKD patient. very effective in preventing progression of renal dysfunc- tion because the total volume of contrast medium was markedly less than that in the standard EVT procedure. Disclosures Furthermore, the image quality yielded by DSA was ac- ceptable (Figures 2 and 3). This method of DSA with di- Conflicts of interest: The authors declare that there are luted contrast medium produces angiographic images with no conflicts of interest. very high sensitivity, enhanced image contrast, and re- Research ethics: All procedures were performed in accor- duced edge gain. Using the adjusted DSA parameters (Ta- dance with the ethical standards of the institutional and/or ble), we obtained high-resolution angiographic images national research committee and with the 1964 Declara- with diluted contrast medium. Generally, we use a 1:10 tion of Helsinki and its later amendments or comparable dilution of contrast medium because it is easy to prepare ethical standards. Informed consent was obtained from the and results in satisfactory angiographic images, even in patient described in the case report. BTK vessels. A valuable advantage of DSA with diluted contrast medium is that no special devices are required if References the DSA parameters are adjusted appropriately. 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