Predictors of Restenosis After Drug-Coated Balloon Angioplasty for Femoropopliteal Chronic Occlusion Lesions

Predictors of Restenosis After Drug-Coated Balloon Angioplasty for Femoropopliteal Chronic Occlusion Lesions | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Predictors of Restenosis After Drug-Coated Balloon Angioplasty for Femoropopliteal Chronic Occlusion Lesions YUKI SHIMA, Mihoko Sato, Gakuto Bando, Narumi Irie, Kazunori Mushiake, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7511977/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Oct, 2025 Read the published version in CVIR Endovascular → Version 1 posted 4 You are reading this latest preprint version Abstract Background Drug-coated balloons (DCBs) are widely used in endovascular therapy. While dissection angle and minimum lumen area (MLA) assessed by intravascular ultrasound (IVUS) are known predictors of restenosis, their specific role after DCB angioplasty remains to be fully elucidated. We aimed to identify predictors of restenosis following DCB angioplasty using IVUS findings. Methods We retrospectively enrolled 36 peripheral artery disease patients undergoing DCB angioplasty (Jan 2021–Dec 2023). We evaluated IVUS images post-guidewire and post-DCB at 3-cm intervals, classifying cross-sections by MLA/external elastic membrane area (EEMA) ratio: >50%, 40–50%, and < 40%. Primary patency at 1 year post-DCB was the primary outcome. Restenosis was objectively determined by a peak systolic velocity ratio of 2.4 on duplex ultrasound, and assessing each cross-sectional images. Results A total of 262 cross-sectional images were acquired and subsequently classified into three distinct groups based on their MLA/EEMA ratio: >50% (n = 125), 40–50% (n = 85), and 50% group (94.0% vs. 84.2% vs. 73.3%, log-rank p = 0.005). Specifically, for dissection angles > 60°, patency was markedly better in the MLA/EEMA > 50% group (93.3% vs. 75.0% vs. 55.6%, log-rank p = 0.03). Dissection angles < 60° showed no significant patency differences (93.9% vs. 88.0% vs. 84.2%, log-rank p = 0.14). Conclusions The MLA/EEMA ratio and the degree of dissection angle may be predictors of primary patency following DCB angioplasty. These findings suggest that optimized vessel preparation strategies can effectively mitigate the adverse clinical impact of dissection. peripheral artery disease endovascular therapy drug-coated balloon intravascular ultrasound Figures Figure 1 Figure 2 Introduction Contemporary clinical guidelines advocate for the utilization of drug-coated balloon (DCB) angioplasty in the management of femoropopliteal lesions [ 1 , 2 ]. Commendable patency rates have been documented following DCB angioplasty, extending even to instances of chronic total occlusion (CTO), which represents a particularly intricate lesion morphology [ 3 , 4 ]. Within the specific context of CTO lesions, intraluminal DCB angioplasty has demonstrated superiority compared to subintimal approaches [ 5 ]. Consequently, the judicious selection of an appropriate guidewire route is paramount for the achievement of sustained primary patency and the prevention of severe iatrogenic dissection in CTO lesions [ 6 ]. Intravascular ultrasound (IVUS) serves as a potent diagnostic modality, furnishing critical information such as vessel diameter, guidewire trajectory, dissection morphology, calcification burden, and postprocedural luminal dimensions, thereby constituting an indispensable asset for enhancing endovascular therapy (EVT) outcomes. Prior research has indicated that a greater minimum lumen area (MLA), as quantitatively assessed by IVUS following DCB angioplasty, is associated with a reduced incidence of restenosis [ 7 ]. Nevertheless, the magnitude of the MLA is intrinsically modulated by vessel diameter and the extent of calcification, both established predictors of restenosis after DCB angioplasty [ 7 ]. Moreover, the dissection angle has been demonstrated to correlate with primary patency rates subsequent to DCB angioplasty [ 8 , 9 ]. The purpose of this study was to elucidate the comprehensive predictors of restenosis following DCB angioplasty, drawing upon detailed IVUS findings. Methods Study Population and Design We conducted a single-center, retrospective cohort study of 36 patients with peripheral artery disease defined as Rutherford class 2–5. All patients underwent initial EVT with DCB angioplasty for femoropopliteal CTOs from January 2021 to December 2023, using Ranger (Boston Scientific Corporation, Marlborough, MA, USA) or IN.PACT Admiral (Medtronic Vascular, Santa Clara, CA, USA) DCBs. IVUS images, acquired post-guidewire and post-DCB, were analyzed at 3-cm intervals. Cross-sectional images were stratified into three groups based on the MLA/external elastic membrane area (EEMA) ratio: >50%, 40–50%, and < 40%. Patients had symptomatic atherosclerosis from the superficial femoral artery to the proximal (P1) popliteal artery. Exclusion criteria were absence of atherosclerosis, Rutherford class 0 or 6, mid (P2) or distal (P3) popliteal lesions, life expectancy < 1 year, advanced malignancy, and acute limb ischemia. All patients provided informed consent. The study received institutional ethics committee approval. Procedural Protocol Procedural Protocol EVT was executed via ipsilateral or contralateral approach originating from the common femoral artery, utilizing a 5-F or 6-F guiding sheath. Unfractionated heparin served as the anticoagulant agent. Antegrade access was achieved employing 0.014-, 0.018-, or 0.035-inch guidewires with adjunct support catheters; a retrograde approach was implemented as clinical necessity dictated. Following guidewire passage, the trajectory of the guidewire was meticulously monitored via IVUS; in instances where a subintimal route was identified, intraplaque wiring was subsequently performed. The categorization of guidewire routes (i.e., intraplaque, subintimal, or intramedial) was rigorously established based on IVUS findings [ 10 ]. Predilation was universally conducted in all patients, guided by either angiographic or IVUS observations. The entirety of the lesion was initially dilated with a smaller 3.0- or 4.0-mm balloon, succeeded by predilation with an optimally sized balloon. Contingent upon IVUS findings, supplementary balloon dilation was performed using either a scoring balloon or a high-pressure balloon. The duration of dilation was primarily at the operator’s discretion but maintained a minimum of one minute for all patients. DCB angioplasty was undertaken only after confirming, to the maximum extent feasible that the residual stenosis remained below 50% and the degree of dissection was inferior to grade D [ 11 , 12 ]. The selection of devices for EVT and the subsequent postprocedural management, including antithrombotic regimens such as antiplatelets or anticoagulants, were determined by the discretion of the treating physician. The recommended antiplatelet therapy comprised long-term aspirin (100 mg/day) in conjunction with clopidogrel (75 mg/day) and/or cilostazol (100 or 200 mg/day) [ 13 ]. Dual antiplatelet therapy was maintained for a minimum duration of 1 month post-EVT. Study Endpoints and Definitions The primary outcome measure established for this study was 1-year primary patency, defined as the absence of restenosis. Restenosis was objectively determined by a peak systolic velocity ratio of 2.4 on duplex ultrasound. Evaluation of target vessel patency was conducted at 6-month intervals for patients presenting with claudication. For patients afflicted with chronic limb-threatening ischemia, follow-up assessments were performed more frequently, ranging from monthly to every several months, primarily owing to the imperative for consistent wound assessment over a 1-year period. Patients with claudication specifically underwent follow-up examinations s at 6 and 12 months subsequent to their EVT. Examinations were performed duplex ultrasound and ankle brachial index, and assessing each cross-sectional images. IVUS examinations, encompassing both baseline and postprocedural assessments, were performed utilizing the AnteOwl system (Terumo, Tokyo, Japan), with image acquisition achieved via automated pullback through the target lesion. EEMA was precisely quantified at the corresponding site of MLA. Figure 1 shows the details of definitions in this study. Two independent, experienced cardiologists (Y.S. and N.T.), who remained blinded to all clinical and procedural data, meticulously classified all relevant IVUS parameters based on their individual evaluations and subsequent mutual consensus. In instances of divergence, a definitive opinion was rendered by a third consulting cardiologist (K.M.). All parameter analyses strictly conformed to the guidelines outlined in the current clinical expert consensus document concerning EVT imaging [ 14 ]. Statistical Analysis Categorical variables were subjected to comparison utilizing the chi-square test. Continuous variables, quantitatively expressed as mean ± SD, underwent comparative analysis using Student’s t-test or the Wilcoxon rank-sum test, contingent upon their distributional properties. The Kolmogorov–Smirnov test was rigorously applied to ascertain the normality of the distribution for all quantitative variables. Cumulative incidence was estimated employing the Kaplan–Meier method, with differences rigorously assessed via the log-rank test. A p -value of < 0.05 was established as the threshold for statistical significance. All statistical computations were executed using JMP version 18.0 software (SAS Institute, Cary, NC, USA). Results Baseline characteristics Table 1 delineates the baseline characteristics of the study cohort. A total of 262 cross-sectional images were acquired and subsequently classified into three distinct groups based on their MLA/EEMA ratio: >50% (n = 125), 40–50% (n = 85), and < 40% (n = 52). The corresponding baseline patient and lesion characteristics, stratified by these cross-sectional image classifications, are comprehensively summarized in Table 2 . Comparative analysis across the three MLA/EEMA ratio groups revealed no statistically significant differences in the prevalence of hemodialysis (28.8% vs. 17.7% vs. 25.0%, p = 0.39). However, there were significant differences in the prevalence of chronic limb-threatening ischemia (47.2% vs. 30.6% vs. 36.5%, p = 0.047) or diabetes mellitus (48.0% vs. 43.5% vs. 65.4%, p = 0.04). Moreover, a significantly elevated rate of occluded lesions was observed within the MLA/EEMA < 40% group (45.6% vs. 63.5% vs. 75.0%, p < 0.001). Table 1 Baseline demographic and clinical characteristics of patients with femoropopliteal chronic occlusion lesions. Patients, n 36 Age, yrs. 79.8 ± 7.5 Males, n (%) 25 (69.4) BMI 21.8 ± 3.8 Hypertension, n (%) 29 (80.5) Diabetes mellitus, n (%) 17 (47.2) Hyperlipidemia, n (%) 21 (58.3) Hemodialysis, n (%) 8 (22.2) Smoking history, n (%) 19 (52.7) CLTI, n (%) 13 (36.1) BTK runoff vessels (n) 2.09 ± 0.75 Lesion length (mm) 210.2 ± 73.9 Occlusion length (mm) 109.6 ± 78.5 Values are expressed as mean ± standard deviation (SD) or percentage (%), as indicated. BMI, body mass index; CLTI, chronic limb-threatening ischemia; BTK, below-the-knee. Table 2 Patient and lesion characteristics by cross-sectional image analysis of femoropopliteal chronic occlusion lesions. MLA/EEMA ratio > 50% MLA/EEMA ratio of 40–50% MLA/EEMA < 40% p Sections, n 125 85 52 Age 74.1 ± 6.5 77 ± 6.5 78.2 ± 7.0 0.002 Males, n (%) 81 (64.8) 60 (70.1) 33 (63.4) 0.32 Hypertension, n (%) 103 (82.4) 72 (84.7) 43 (82.7) 0.9 Diabetes mellitus, n (%) 60 (48.0) 37 (43.5) 34 (65.4) 0.04 Hyperlipidemia, n (%) 71 (56.8) 60 (70.6) 37 (71.2) 0.06 Smoking history, n (%) 83 (66.4) 50 (58.8) 25 (48.1) 0.07 Hemodialysis, n (%) 36 (28.8) 15 (17.7) 13 (25.0) 0.18 Occluded lesion, n (%) 57 (45.6) 54 (63.5) 39 (75.0) < 0.001 CLTI, (%) 59 (47.2) 26 (30.6) 19 (36.5) 0.04 MLA, mm 2 15.5 ± 3.9 13.3 ± 2.9 11.1 ± 2.6 < 0.01 EEMA, mm2 26.9 ± 6.8 29.9 ± 6.7 36.4 ± 6.8 0.002 EEM 6mm, n (%) 57 (45.6) 51 (60.0) 34 (65.4) 0.02 Dissection angle > 60°, n (%) 31 (24.8) 25 (29.4) 17 (32.7) 0.53 Severe calcification > 270°, n (%) 15 (12.0) 13(15.3) 9 (17.3) 0.6 INPACT DCB, n (%) 65 (52.0) 38 (44.7) 26 (50.0) 0.58 Ranger DCB, n (%) 60 (48.0) 47 (55.3) 26 (50.0) 0.58 Bailout stenting, n (%) 0 (0) 0 (0) 0 (0) Data are shown as mean ± standard deviation or percentage (%), unless noted. CLTI, chronic limb-threatening ischemia; MLA, minimum lumen area; EEMA, external elastic membrane area; EEM external elastic membrane; DCB, drug-coated balloon. Outcome measures All guidewires passed through the intraplaque route. Across the three comparative groups, the mean EEMA was significantly larger within the MLA/EEMA 6 mm) was also significantly elevated in the MLA/EEMA < 40% group (45.6% vs. 60.0% vs. 65.4%, p = 0.02). Conversely, no statistically significant disparities were observed concerning the degree of dissection (29.0° vs. 37.3° vs. 43.3°, p = 0.25) or the prevalence of severe calcification (12.0% vs. 15.3% vs. 17.3%, p = 0.61). As presented in Fig. 2 , Kaplan–Meier estimations illustrate the cumulative primary patency rates. Primary patency was demonstrably and statistically significantly higher in the MLA/EEMA > 50% cohort compared to the 40–50% and < 40% groups (94.0% vs. 84.2% vs. 73.3%, log-rank p = 0.005). Further stratification by dissection angle revealed that in cross-sectional images with a dissection angle exceeding 60 degrees, the patency rate remained significantly elevated in the MLA/EEMA > 50% group (93.3% vs. 75.0% vs. 55.6%, log-rank p = 0.03). Conversely, for cross-sectional images characterized by a dissection angle of less than 60 degrees, no statistically significant disparity in primary patency was discernible across the three groups (93.9% vs. 88.0% vs. 84.2%, log-rank p = 0.14). Discussion The main findings derived from this investigation are as follows: (1) the attainment of a MLA/EEMA ratio > 50% consistently portends favorable primary patency, even within the challenging context of CTO lesions; (2) optimal patency can be anticipated even in the presence of dissection, provided the MLA/EEMA ratio exceeds 50%. Conversely, a limited dissection angle may attenuate the influence of residual lumen area on long-term patency. Recent investigations by Ko et al. have elucidated that IVUS-guided EVT significantly enhances the clinical outcomes of DCB angioplasty. The discernible advantages of IVUS guidance encompass superior detection of calcifications and arterial dissections, coupled with the capability for precise quantification of vessel dimensions and the identification of optimal landing zones [ 15 ]. Furthermore, Kurata et al. have reported a significant association between DCBs sized according to IVUS-EEM dimensions, as opposed to angiographic lumen or IVUS-lumen dimensions, and a diminished risk of restenosis following EVT for femoropopliteal lesions [ 16 ]. Specifically, a larger MLA has been posited to correlate with a reduced incidence of restenosis at 1 year post-DCB angioplasty [ 7 ]. In congruence with these prior observations, the present study demonstrates robust 1-year primary patency within the MLA/EEMA > 50% cohort, juxtaposed with suboptimal patency in the MLA/EEMA < 40% group. Given that residual stenosis constitutes an independent predictor of restenosis within 1 year following DCB angioplasty [ 17 ], the judicious selection of an appropriate balloon based on comprehensive IVUS measurements is demonstrably paramount. Although previous reports have posited an association between primary patency and MLA, dissection angle, and calcification [ 7 , 8 , 18 ], a comprehensive evaluation of these factors in combination has been absent. To the best of our knowledge, the present investigation represents the first study to synergistically assess IVUS findings following DCB angioplasty. Our findings indicate that the impact of dissection on patency is attenuated when an adequate lumen area is achieved, yet becomes pronounced when optimal lumen gain is not attained. Importantly, favorable patency outcomes can still be anticipated even with a suboptimal lumen area if the associated dissection angle is minimal. It is necessary to minimize the angle of dissection, and the appropriate selection of wires and balloon expansion strategies is essential to prevent severe dissection. Central wiring, employed intraluminally and confirmed by IVUS in all lesions in this study, can effectively preclude the formation of severe dissections. Furthermore, during balloon dilation, careful consideration should be given to extended inflation times and the utilization of scoring balloons, as these interventions have been suggested to reduce the risk of severe dissection [ 19 , 20 ]. Our DCB angioplasty protocol used IVUS-measured distal reference vessel diameters for balloon sizing, aiming to prevent vessel over-injury. This strategy, however, may lead to under-dilation of larger proximal segments in long lesions, potentially explaining the greater proportion of larger EEMs in the MLA/EEMA < 40% group. Optimal patency may require adequately dilating these proximal vessel portions. While severe calcification is a known restenosis predictor, we did not observe this in our cohort. This could be due to successful lumen gain in many cases, but warrants further investigation in longer-term studies. Limitations Our study presents four primary limitations. First, its single-center, retrospective, observational nature and small patient sample raise concerns about selection bias affecting the conclusions. Second, operator discretion in DCB angioplasty, without a predefined protocol, may have introduced selection bias. Third, experienced cardiologists, not an external core laboratory, interpreted angiographic and IVUS findings. We mitigated measurement bias by adhering to the current consensus document [ 14 ]. Lastly, we did not utilize atherectomy devices. Conclusions The MLA/EEMA ratio and the degree of dissection angle may be independent predictors of primary patency. Furthermore, these findings suggest that meticulous vessel preparation strategies are instrumental in minimizing the detrimental consequences of dissection. Abbreviations DCB Drug-coated balloon CTO Chronic total occlusion (CTO) IVUS Intravascular ultrasound EVT Endovascular therapy MLA Minimum lumen area EEMA External elastic membrane area Declarations Ethics approval and consent to participate All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional review board, independent ethics committee, or research ethics board applicable to each study site, and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Consent for publication For this type of study, consent for publication is not required. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. Competing interests The authors declare that they have no competing interests. Funding None. Authors ’ contributions YS is the corresponding author and wrote the paper. MS, GB, NI, KM, NI, and HT performed the procedures and pre- and post-procedure follow-ups. KK drafted the manuscript and revised it critically for important intellectual content. KK provided the final approval of the submitted manuscript. All authors read and approved the final manuscript. Acknowledgment We are grateful to Miho Kobayashi for editing assistance. Authors ’ information Not applicable. References Aboyans V, Ricco JB, Bartelink MEL, Björck M, Brodmann M, Cohnert T, et al. 2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries. 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Cite Share Download PDF Status: Published Journal Publication published 28 Oct, 2025 Read the published version in CVIR Endovascular → Version 1 posted Reviewers agreed at journal 11 Sep, 2025 Reviewers invited by journal 03 Sep, 2025 Editor assigned by journal 03 Sep, 2025 First submitted to journal 01 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7511977","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":509694216,"identity":"0878c460-344d-47db-a3f2-4b6704c8cd76","order_by":0,"name":"YUKI SHIMA","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9ElEQVRIiWNgGAWjYFACHoYDDAz/ePjZGxiYYWIGRGg5ICPZc4AELUBwwMbgRgJCC15gcP7swUM3au7wSM58Y/i5oMKGgb+9gaG4AJ+WG3kJh3OOPePhl84xlp5xJo1B4swBBuMZeLXwGBzOYWPmkZydYyDN23aYwUAigcGYB6/DzgC1/GPmMbh5xvg3cVoO5Bgczm07zAO0zow4WyRvgLT0pfFI9qSVWfOcSeOROHOwAa9f+M6fMf6c883Gnp/98ObbPBU2cvztzceM8YWYwgE4kwMcgUAnMbYZ49HBIN8AZ7I/gLGYH+PTMgpGwSgYBSMOAAAZF01hVj6XJwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-3442-3637","institution":"Kurashiki Central Hospital: Kurashiki Chuo Byoin","correspondingAuthor":true,"prefix":"","firstName":"YUKI","middleName":"","lastName":"SHIMA","suffix":""},{"id":509694217,"identity":"cbdeeafc-5940-4ec3-b4c0-17239a460a4e","order_by":1,"name":"Mihoko Sato","email":"","orcid":"","institution":"Kurashiki Central Hospital: Kurashiki Chuo Byoin","correspondingAuthor":false,"prefix":"","firstName":"Mihoko","middleName":"","lastName":"Sato","suffix":""},{"id":509694218,"identity":"43d865b6-8326-4c21-8a7b-90f51a105298","order_by":2,"name":"Gakuto Bando","email":"","orcid":"","institution":"Kurashiki Central Hospital: Kurashiki Chuo Byoin","correspondingAuthor":false,"prefix":"","firstName":"Gakuto","middleName":"","lastName":"Bando","suffix":""},{"id":509694219,"identity":"cfad07dd-a2a0-4aa7-80ee-fc5b3c737427","order_by":3,"name":"Narumi Irie","email":"","orcid":"","institution":"Kurashiki Central Hospital: Kurashiki Chuo Byoin","correspondingAuthor":false,"prefix":"","firstName":"Narumi","middleName":"","lastName":"Irie","suffix":""},{"id":509694220,"identity":"59de60b0-2201-4dff-8f93-7a9c8e477502","order_by":4,"name":"Kazunori Mushiake","email":"","orcid":"","institution":"Kurashiki Central Hospital: Kurashiki Chuo Byoin","correspondingAuthor":false,"prefix":"","firstName":"Kazunori","middleName":"","lastName":"Mushiake","suffix":""},{"id":509694221,"identity":"59281886-e6b1-4f36-83e8-87fca4913568","order_by":5,"name":"Naoya Inoue","email":"","orcid":"","institution":"Kurashiki Central Hospital: Kurashiki Chuo Byoin","correspondingAuthor":false,"prefix":"","firstName":"Naoya","middleName":"","lastName":"Inoue","suffix":""},{"id":509694222,"identity":"bfc68578-9d87-46a6-b2b9-fb81cecf09e9","order_by":6,"name":"Hiroyuki Tanaka","email":"","orcid":"","institution":"Kurashiki Central Hospital: Kurashiki Chuo Byoin","correspondingAuthor":false,"prefix":"","firstName":"Hiroyuki","middleName":"","lastName":"Tanaka","suffix":""},{"id":509694223,"identity":"dab86e77-a2f5-4fbb-bc2f-1f1f98ab805d","order_by":7,"name":"Kazushige Kadota","email":"","orcid":"","institution":"Kurashiki Central Hospital: Kurashiki Chuo Byoin","correspondingAuthor":false,"prefix":"","firstName":"Kazushige","middleName":"","lastName":"Kadota","suffix":""}],"badges":[],"createdAt":"2025-09-02 00:37:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7511977/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7511977/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s42155-025-00612-4","type":"published","date":"2025-10-28T15:57:55+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":90984260,"identity":"59d16344-1ece-4bd0-abb7-2149a1f40e15","added_by":"auto","created_at":"2025-09-10 09:41:02","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":419817,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Pre-angiography. IVUS images were analyzed at 3-cm intervals. (b) IVUS image and measurement of EEMA. (c) IVUS image and measurement of MLA. (d) IVUS image and measurement of dissection angle.\u003c/p\u003e\n\u003cp\u003eIVUS, intravascular ultrasound; EEMA, external elastic membrane area; MLA, minimum lumen area.\u003c/p\u003e","description":"","filename":"Figure11.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7511977/v1/28b9f4cd056eb418b17af1c9.jpg"},{"id":90984255,"identity":"e5243bb2-354a-4ffb-86fb-ccaba817b141","added_by":"auto","created_at":"2025-09-10 09:41:02","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":630101,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier curves for 1-year primary patency following drug-coated balloon angioplasty. (A) Overall primary patency. (B) Primary patency in cross-sections with a dissection angle \u0026gt;60 degrees. (C) Primary patency in cross-sections with a dissection angle \u0026lt;60 degrees.\u003c/p\u003e","description":"","filename":"Figure2.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7511977/v1/d3a965e0f55fe7fb94256752.jpg"},{"id":95041154,"identity":"9527d0b2-4c4c-4a05-bd36-dfafb414f142","added_by":"auto","created_at":"2025-11-03 16:10:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1656334,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7511977/v1/2c8dc154-6e0f-4c31-ae93-3c3ca7c003bc.pdf"}],"financialInterests":"","formattedTitle":"Predictors of Restenosis After Drug-Coated Balloon Angioplasty for Femoropopliteal Chronic Occlusion Lesions","fulltext":[{"header":"Introduction","content":"\u003cp\u003eContemporary clinical guidelines advocate for the utilization of drug-coated balloon (DCB) angioplasty in the management of femoropopliteal lesions [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Commendable patency rates have been documented following DCB angioplasty, extending even to instances of chronic total occlusion (CTO), which represents a particularly intricate lesion morphology [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Within the specific context of CTO lesions, intraluminal DCB angioplasty has demonstrated superiority compared to subintimal approaches [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Consequently, the judicious selection of an appropriate guidewire route is paramount for the achievement of sustained primary patency and the prevention of severe iatrogenic dissection in CTO lesions [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIntravascular ultrasound (IVUS) serves as a potent diagnostic modality, furnishing critical information such as vessel diameter, guidewire trajectory, dissection morphology, calcification burden, and postprocedural luminal dimensions, thereby constituting an indispensable asset for enhancing endovascular therapy (EVT) outcomes. Prior research has indicated that a greater minimum lumen area (MLA), as quantitatively assessed by IVUS following DCB angioplasty, is associated with a reduced incidence of restenosis [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Nevertheless, the magnitude of the MLA is intrinsically modulated by vessel diameter and the extent of calcification, both established predictors of restenosis after DCB angioplasty [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Moreover, the dissection angle has been demonstrated to correlate with primary patency rates subsequent to DCB angioplasty [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The purpose of this study was to elucidate the comprehensive predictors of restenosis following DCB angioplasty, drawing upon detailed IVUS findings.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy Population and Design\u003c/h2\u003e\u003cp\u003eWe conducted a single-center, retrospective cohort study of 36 patients with peripheral artery disease defined as Rutherford class 2\u0026ndash;5. All patients underwent initial EVT with DCB angioplasty for femoropopliteal CTOs from January 2021 to December 2023, using Ranger (Boston Scientific Corporation, Marlborough, MA, USA) or IN.PACT Admiral (Medtronic Vascular, Santa Clara, CA, USA) DCBs. IVUS images, acquired post-guidewire and post-DCB, were analyzed at 3-cm intervals. Cross-sectional images were stratified into three groups based on the MLA/external elastic membrane area (EEMA) ratio: \u0026gt;50%, 40\u0026ndash;50%, and \u0026lt;\u0026thinsp;40%. Patients had symptomatic atherosclerosis from the superficial femoral artery to the proximal (P1) popliteal artery. Exclusion criteria were absence of atherosclerosis, Rutherford class 0 or 6, mid (P2) or distal (P3) popliteal lesions, life expectancy\u0026thinsp;\u0026lt;\u0026thinsp;1 year, advanced malignancy, and acute limb ischemia. All patients provided informed consent. The study received institutional ethics committee approval.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eProcedural Protocol\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003eProcedural Protocol\u003c/div\u003e\u003cp\u003eEVT was executed via ipsilateral or contralateral approach originating from the common femoral artery, utilizing a 5-F or 6-F guiding sheath. Unfractionated heparin served as the anticoagulant agent. Antegrade access was achieved employing 0.014-, 0.018-, or 0.035-inch guidewires with adjunct support catheters; a retrograde approach was implemented as clinical necessity dictated. Following guidewire passage, the trajectory of the guidewire was meticulously monitored via IVUS; in instances where a subintimal route was identified, intraplaque wiring was subsequently performed. The categorization of guidewire routes (i.e., intraplaque, subintimal, or intramedial) was rigorously established based on IVUS findings [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Predilation was universally conducted in all patients, guided by either angiographic or IVUS observations. The entirety of the lesion was initially dilated with a smaller 3.0- or 4.0-mm balloon, succeeded by predilation with an optimally sized balloon. Contingent upon IVUS findings, supplementary balloon dilation was performed using either a scoring balloon or a high-pressure balloon. The duration of dilation was primarily at the operator\u0026rsquo;s discretion but maintained a minimum of one minute for all patients. DCB angioplasty was undertaken only after confirming, to the maximum extent feasible that the residual stenosis remained below 50% and the degree of dissection was inferior to grade D [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The selection of devices for EVT and the subsequent postprocedural management, including antithrombotic regimens such as antiplatelets or anticoagulants, were determined by the discretion of the treating physician. The recommended antiplatelet therapy comprised long-term aspirin (100 mg/day) in conjunction with clopidogrel (75 mg/day) and/or cilostazol (100 or 200 mg/day) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Dual antiplatelet therapy was maintained for a minimum duration of 1 month post-EVT.\u003c/p\u003e\n\u003ch3\u003eStudy Endpoints and Definitions\u003c/h3\u003e\n\u003cp\u003eThe primary outcome measure established for this study was 1-year primary patency, defined as the absence of restenosis. Restenosis was objectively determined by a peak systolic velocity ratio of 2.4 on duplex ultrasound. Evaluation of target vessel patency was conducted at 6-month intervals for patients presenting with claudication. For patients afflicted with chronic limb-threatening ischemia, follow-up assessments were performed more frequently, ranging from monthly to every several months, primarily owing to the imperative for consistent wound assessment over a 1-year period. Patients with claudication specifically underwent follow-up examinations s at 6 and 12 months subsequent to their EVT. Examinations were performed duplex ultrasound and ankle brachial index, and assessing each cross-sectional images.\u003c/p\u003e\u003cp\u003eIVUS examinations, encompassing both baseline and postprocedural assessments, were performed utilizing the AnteOwl system (Terumo, Tokyo, Japan), with image acquisition achieved via automated pullback through the target lesion. EEMA was precisely quantified at the corresponding site of MLA. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the details of definitions in this study.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eTwo independent, experienced cardiologists (Y.S. and N.T.), who remained blinded to all clinical and procedural data, meticulously classified all relevant IVUS parameters based on their individual evaluations and subsequent mutual consensus. In instances of divergence, a definitive opinion was rendered by a third consulting cardiologist (K.M.). All parameter analyses strictly conformed to the guidelines outlined in the current clinical expert consensus document concerning EVT imaging [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eCategorical variables were subjected to comparison utilizing the chi-square test. Continuous variables, quantitatively expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, underwent comparative analysis using Student\u0026rsquo;s t-test or the Wilcoxon rank-sum test, contingent upon their distributional properties. The Kolmogorov\u0026ndash;Smirnov test was rigorously applied to ascertain the normality of the distribution for all quantitative variables. Cumulative incidence was estimated employing the Kaplan\u0026ndash;Meier method, with differences rigorously assessed via the log-rank test. A \u003cem\u003ep\u003c/em\u003e-value of \u0026lt;\u0026thinsp;0.05 was established as the threshold for statistical significance. All statistical computations were executed using JMP version 18.0 software (SAS Institute, Cary, NC, USA).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eBaseline characteristics\u003c/h2\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e delineates the baseline characteristics of the study cohort. A total of 262 cross-sectional images were acquired and subsequently classified into three distinct groups based on their MLA/EEMA ratio: \u0026gt;50% (n\u0026thinsp;=\u0026thinsp;125), 40\u0026ndash;50% (n\u0026thinsp;=\u0026thinsp;85), and \u0026lt;\u0026thinsp;40% (n\u0026thinsp;=\u0026thinsp;52). The corresponding baseline patient and lesion characteristics, stratified by these cross-sectional image classifications, are comprehensively summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Comparative analysis across the three MLA/EEMA ratio groups revealed no statistically significant differences in the prevalence of hemodialysis (28.8% vs. 17.7% vs. 25.0%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.39). However, there were significant differences in the prevalence of chronic limb-threatening ischemia (47.2% vs. 30.6% vs. 36.5%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.047) or diabetes mellitus (48.0% vs. 43.5% vs. 65.4%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04). Moreover, a significantly elevated rate of occluded lesions was observed within the MLA/EEMA\u0026thinsp;\u0026lt;\u0026thinsp;40% group (45.6% vs. 63.5% vs. 75.0%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline demographic and clinical characteristics of patients with femoropopliteal chronic occlusion lesions.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatients, n\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, yrs.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e79.8\u0026thinsp;\u0026plusmn;\u0026thinsp;7.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMales, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25 (69.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29 (80.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes mellitus, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (47.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHyperlipidemia, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (58.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemodialysis, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (22.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking history, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 (52.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCLTI, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (36.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBTK runoff vessels (n)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.09\u0026thinsp;\u0026plusmn;\u0026thinsp;0.75\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLesion length (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e210.2\u0026thinsp;\u0026plusmn;\u0026thinsp;73.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOcclusion length (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e109.6\u0026thinsp;\u0026plusmn;\u0026thinsp;78.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eValues are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) or percentage (%), as indicated. BMI, body mass index; CLTI, chronic limb-threatening ischemia; BTK, below-the-knee.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePatient and lesion characteristics by cross-sectional image analysis of femoropopliteal chronic occlusion lesions.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMLA/EEMA ratio\u0026thinsp;\u0026gt;\u0026thinsp;50%\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMLA/EEMA ratio of 40\u0026ndash;50%\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMLA/EEMA\u0026thinsp;\u0026lt;\u0026thinsp;40%\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSections, n\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e125\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e74.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e77\u0026thinsp;\u0026plusmn;\u0026thinsp;6.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e78.2\u0026thinsp;\u0026plusmn;\u0026thinsp;7.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMales, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e81 (64.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60 (70.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e33 (63.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.32\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e103 (82.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e72 (84.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e43 (82.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes mellitus, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60 (48.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37 (43.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e34 (65.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHyperlipidemia, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e71 (56.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60 (70.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e37 (71.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking history, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e83 (66.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50 (58.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e25 (48.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemodialysis, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36 (28.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15 (17.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13 (25.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.18\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOccluded lesion, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e57 (45.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e54 (63.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e39 (75.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCLTI, (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e59 (47.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26 (30.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19 (36.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMLA, mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEEMA, mm2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e36.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEEM\u0026thinsp;\u0026lt;\u0026thinsp;5mm, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (12.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (5.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (5.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.21\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEEM 5\u0026ndash;6mm, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e53 (42.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29 (34.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14 (26.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.13\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEEM\u0026thinsp;\u0026gt;\u0026thinsp;6mm, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e57 (45.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e51 (60.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e34 (65.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDissection angle\u0026thinsp;\u0026gt;\u0026thinsp;60\u0026deg;, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31 (24.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25 (29.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17 (32.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.53\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSevere calcification\u0026thinsp;\u0026gt;\u0026thinsp;270\u0026deg;, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (12.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13(15.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (17.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eINPACT DCB, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e65 (52.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e38 (44.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26 (50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.58\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRanger DCB, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60 (48.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e47 (55.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26 (50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.58\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBailout stenting, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eData are shown as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or percentage (%), unless noted. CLTI, chronic limb-threatening ischemia; MLA, minimum lumen area; EEMA, external elastic membrane area; EEM external elastic membrane; DCB, drug-coated balloon.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eOutcome measures\u003c/h3\u003e\n\u003cp\u003eAll guidewires passed through the intraplaque route. Across the three comparative groups, the mean EEMA was significantly larger within the MLA/EEMA\u0026thinsp;\u0026lt;\u0026thinsp;40% cohort (26.9 mm\u003csup\u003e2\u003c/sup\u003e vs. 29.9 mm\u003csup\u003e2\u003c/sup\u003e vs. 36.4 mm\u003csup\u003e2\u003c/sup\u003e, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02). Commensurately, the proportion of vessels exhibiting a large diameter (EEM\u0026thinsp;\u0026gt;\u0026thinsp;6 mm) was also significantly elevated in the MLA/EEMA\u0026thinsp;\u0026lt;\u0026thinsp;40% group (45.6% vs. 60.0% vs. 65.4%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02). Conversely, no statistically significant disparities were observed concerning the degree of dissection (29.0\u0026deg; vs. 37.3\u0026deg; vs. 43.3\u0026deg;, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.25) or the prevalence of severe calcification (12.0% vs. 15.3% vs. 17.3%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.61).\u003c/p\u003e\u003cp\u003eAs presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Kaplan\u0026ndash;Meier estimations illustrate the cumulative primary patency rates. Primary patency was demonstrably and statistically significantly higher in the MLA/EEMA\u0026thinsp;\u0026gt;\u0026thinsp;50% cohort compared to the 40\u0026ndash;50% and \u0026lt;\u0026thinsp;40% groups (94.0% vs. 84.2% vs. 73.3%, log-rank \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005). Further stratification by dissection angle revealed that in cross-sectional images with a dissection angle exceeding 60 degrees, the patency rate remained significantly elevated in the MLA/EEMA\u0026thinsp;\u0026gt;\u0026thinsp;50% group (93.3% vs. 75.0% vs. 55.6%, log-rank \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.03). Conversely, for cross-sectional images characterized by a dissection angle of less than 60 degrees, no statistically significant disparity in primary patency was discernible across the three groups (93.9% vs. 88.0% vs. 84.2%, log-rank \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.14).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe main findings derived from this investigation are as follows: (1) the attainment of a MLA/EEMA ratio\u0026thinsp;\u0026gt;\u0026thinsp;50% consistently portends favorable primary patency, even within the challenging context of CTO lesions; (2) optimal patency can be anticipated even in the presence of dissection, provided the MLA/EEMA ratio exceeds 50%. Conversely, a limited dissection angle may attenuate the influence of residual lumen area on long-term patency.\u003c/p\u003e\u003cp\u003eRecent investigations by Ko et al. have elucidated that IVUS-guided EVT significantly enhances the clinical outcomes of DCB angioplasty. The discernible advantages of IVUS guidance encompass superior detection of calcifications and arterial dissections, coupled with the capability for precise quantification of vessel dimensions and the identification of optimal landing zones [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Furthermore, Kurata et al. have reported a significant association between DCBs sized according to IVUS-EEM dimensions, as opposed to angiographic lumen or IVUS-lumen dimensions, and a diminished risk of restenosis following EVT for femoropopliteal lesions [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Specifically, a larger MLA has been posited to correlate with a reduced incidence of restenosis at 1 year post-DCB angioplasty [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In congruence with these prior observations, the present study demonstrates robust 1-year primary patency within the MLA/EEMA\u0026thinsp;\u0026gt;\u0026thinsp;50% cohort, juxtaposed with suboptimal patency in the MLA/EEMA\u0026thinsp;\u0026lt;\u0026thinsp;40% group. Given that residual stenosis constitutes an independent predictor of restenosis within 1 year following DCB angioplasty [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], the judicious selection of an appropriate balloon based on comprehensive IVUS measurements is demonstrably paramount.\u003c/p\u003e\u003cp\u003eAlthough previous reports have posited an association between primary patency and MLA, dissection angle, and calcification [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], a comprehensive evaluation of these factors in combination has been absent. To the best of our knowledge, the present investigation represents the first study to synergistically assess IVUS findings following DCB angioplasty. Our findings indicate that the impact of dissection on patency is attenuated when an adequate lumen area is achieved, yet becomes pronounced when optimal lumen gain is not attained. Importantly, favorable patency outcomes can still be anticipated even with a suboptimal lumen area if the associated dissection angle is minimal. It is necessary to minimize the angle of dissection, and the appropriate selection of wires and balloon expansion strategies is essential to prevent severe dissection. Central wiring, employed intraluminally and confirmed by IVUS in all lesions in this study, can effectively preclude the formation of severe dissections. Furthermore, during balloon dilation, careful consideration should be given to extended inflation times and the utilization of scoring balloons, as these interventions have been suggested to reduce the risk of severe dissection [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Our DCB angioplasty protocol used IVUS-measured distal reference vessel diameters for balloon sizing, aiming to prevent vessel over-injury. This strategy, however, may lead to under-dilation of larger proximal segments in long lesions, potentially explaining the greater proportion of larger EEMs in the MLA/EEMA\u0026thinsp;\u0026lt;\u0026thinsp;40% group. Optimal patency may require adequately dilating these proximal vessel portions. While severe calcification is a known restenosis predictor, we did not observe this in our cohort. This could be due to successful lumen gain in many cases, but warrants further investigation in longer-term studies.\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eLimitations\u003c/h2\u003e\u003cp\u003eOur study presents four primary limitations. First, its single-center, retrospective, observational nature and small patient sample raise concerns about selection bias affecting the conclusions. Second, operator discretion in DCB angioplasty, without a predefined protocol, may have introduced selection bias. Third, experienced cardiologists, not an external core laboratory, interpreted angiographic and IVUS findings. We mitigated measurement bias by adhering to the current consensus document [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Lastly, we did not utilize atherectomy devices.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe MLA/EEMA ratio and the degree of dissection angle may be independent predictors of primary patency. Furthermore, these findings suggest that meticulous vessel preparation strategies are instrumental in minimizing the detrimental consequences of dissection.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eDCB \u0026nbsp;Drug-coated balloon\u003c/p\u003e\n\u003cp\u003eCTO \u0026nbsp;Chronic total occlusion (CTO)\u003c/p\u003e\n\u003cp\u003eIVUS \u0026nbsp;Intravascular ultrasound\u003c/p\u003e\n\u003cp\u003eEVT \u0026nbsp;Endovascular therapy\u003c/p\u003e\n\u003cp\u003eMLA \u0026nbsp;Minimum lumen area\u003c/p\u003e\n\u003cp\u003eEEMA \u0026nbsp;External elastic membrane area\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional review board, independent ethics committee, or research ethics board applicable to each study site, and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor this type of study, consent for publication is not required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u003c/strong\u003e\u003cstrong\u003e’\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYS is the corresponding author and wrote the paper. MS, GB, NI, KM, NI, and\u003c/p\u003e\n\u003cp\u003eHT performed the procedures and pre- and post-procedure follow-ups. KK drafted the manuscript and revised it critically for important intellectual content. KK provided the final approval of the submitted manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are grateful to Miho Kobayashi for editing assistance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u003c/strong\u003e\u003cstrong\u003e’\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAboyans V, Ricco JB, Bartelink MEL, Bj\u0026ouml;rck M, Brodmann M, Cohnert T, et al. 2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries. 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Clinical outcome of low-dose and high-dose drug-coated balloon angioplasty with intraplaque wiring for femoropopliteal chronic total occlusion lesions. Cardiovasc Interv Ther. 2025;40:337-343.\u003c/li\u003e\n\u003cli\u003eToyoshima T, Takahara M, Iida O, Tomoi Y, Kawasaki D, Tanaka A, et al. Intraluminal vs subintimal drug-coated balloon angioplasty for the treatment of femoropopliteal chronic total occlusions. JACC Cardiovasc Interv. 2024;17:608-618.\u003c/li\u003e\n\u003cli\u003eShimada T, Shima Y, Miura K, Shimizu H, Takamatsu M, Ikuta A, et al. Impact of guidewire route on severe dissection after balloon angioplasty for femoropopliteal chronic total occlusion lesions: an intravascular ultrasound analysis. Eur J Vasc Surg. 2021;61:830-836.\u003c/li\u003e\n\u003cli\u003eHorie K, Tanaka A, Taguri M, Inoue N. Impact of baseline and postprocedural intravascular ultrasound findings on 1-year primary patency after drug-coated balloon treatment of femoropopliteal lesions. J Endovasc Ther. 2022;29:66-75.\u003c/li\u003e\n\u003cli\u003eKozuki A, Takahara M, Shimizu M, Kijima Y, Nagoshi R, Fujiwara R, et al. Outcomes of dissection angles as predictor of restenosis after drug-coated balloon treatment. J Atheroscler Thromb. 2021;28:954-962.\u003c/li\u003e\n\u003cli\u003eHaraguchi T, Kuramitsu S, Tsujimoto M, Kashima Y, Sato K, Fujita T. Outcomes of non‐flow‐limiting spiral dissection after drug‐coated balloon angioplasty for de novo femoropopliteal lesions. Catheter Cardiovasc Interv. 2024;103:97-105.\u003c/li\u003e\n\u003cli\u003eKawasaki D, Iida O, Fukunaga M, Kato M, Ohkubo N. Wire passages of 0.035-inch looped wire technique for femoropopliteal long total occlusions. J Atheroscler Thromb. 2015;22:1071-1079.\u003c/li\u003e\n\u003cli\u003eFujihara M, Takahara M, Sasaki S, Nanto K, Utsunomiya M, Iida O, et al. Angiographic dissection patterns and patency outcomes after balloon angioplasty for superficial femoral artery disease. J Endovasc Ther. 2017;24:367-375.\u003c/li\u003e\n\u003cli\u003eFeldman DN, Armstrong EJ, Aronow HD, Gigliotti OS, Jaff MR, Klein AJ, et al. SCAI consensus guidelines for device selection in femoral-popliteal arterial interventions. Catheter Cardiovasc Interv. 2018;92:124-140.\u003c/li\u003e\n\u003cli\u003eSoga Y, Iida O, Takahaera M, Hirano K, Suzuki K, Kawasaki D, et al. Two-year life expectancy in patients with critical limb ischemia. JACC Cardiovasc Interv. 2014;7:1444-1449.\u003c/li\u003e\n\u003cli\u003eFujihara M, Kurata N, Yazu Y, Mori S, Tomoi Y, Horie K, et al. Clinical expert consensus document on standards for lower extremity artery disease of imaging modality from the Japan Endovascular Treatment Conference. Cardiovasc Interv Ther. 2022;37:597-612. \u003c/li\u003e\n\u003cli\u003eKo YG, Lee SJ, Ahn CM, Lee SH, Lee YJ, Kim BK, et al. Intravascular ultrasound-guided drug-coated balloon angioplasty for femoropopliteal artery disease: a clinical trial. Eur Heart J. 2024;45:2839-2847.\u003c/li\u003e\n\u003cli\u003eKurata N, Iida O, Takahara M, Asai M, Masuda M, Okamoto S, et al. Clinical impact of the size of drug-coated balloon therapy on restenosis rate in femoropopliteal lesions. J Endovasc Ther, 2023;30:269-280.\u003c/li\u003e\n\u003cli\u003eSoga Y, Takahara M, Iida O, Tomoi Y, Kawasaki D, Tanaka A, et al. Vessel patency and associated factors of drug-coated balloon for femoropopliteal lesion. J Am Heart Assoc 2023;12:e025677.\u003c/li\u003e\n\u003cli\u003eMori S, Takahara M, Nakama T, Tobita K, Hayakawa N, Iwata Y, et al. Impact of calcification on clinical outcomes after drug-coated balloon angioplasty for superficial femoral artery disease: assessment using the peripheral artery calcification scoring system. Catheter Cardiovasc Interv. 2023;101:892-899.\u003c/li\u003e\n\u003cli\u003eTan M, Urasawa K, Koshida R, Haraguuchi T, Kitani S, Igarashi Y, et al. Comparison of angiographic dissection patterns caused by long vs short balloons during balloon angioplasty of chronic femoropopliteal occlusions. J Endovasc Ther. 2018;25:192-200.\u003c/li\u003e\n\u003cli\u003eKarashima E, Yoda S, Yasuda S, Kajiyama S, Ito H, Kaneko T. Usefulness of the \u0026quot;non-slip element\u0026quot; percutaneous transluminal angioplasty balloon in the treatment of femoropopliteal arterial lesions. J Endovasc Ther. 2020;27:102-108.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"cvir-endovascular","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cire","sideBox":"Learn more about [CVIR Endovascular](https://www.springer.com/journal/42155)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/cire/default.aspx","title":"CVIR Endovascular","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"peripheral artery disease, endovascular therapy, drug-coated balloon, intravascular ultrasound","lastPublishedDoi":"10.21203/rs.3.rs-7511977/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7511977/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eDrug-coated balloons (DCBs) are widely used in endovascular therapy. While dissection angle and minimum lumen area (MLA) assessed by intravascular ultrasound (IVUS) are known predictors of restenosis, their specific role after DCB angioplasty remains to be fully elucidated. We aimed to identify predictors of restenosis following DCB angioplasty using IVUS findings.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe retrospectively enrolled 36 peripheral artery disease patients undergoing DCB angioplasty (Jan 2021\u0026ndash;Dec 2023). We evaluated IVUS images post-guidewire and post-DCB at 3-cm intervals, classifying cross-sections by MLA/external elastic membrane area (EEMA) ratio: \u0026gt;50%, 40\u0026ndash;50%, and \u0026lt;\u0026thinsp;40%. Primary patency at 1 year post-DCB was the primary outcome. Restenosis was objectively determined by a peak systolic velocity ratio of 2.4 on duplex ultrasound, and assessing each cross-sectional images.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 262 cross-sectional images were acquired and subsequently classified into three distinct groups based on their MLA/EEMA ratio: \u0026gt;50% (n\u0026thinsp;=\u0026thinsp;125), 40\u0026ndash;50% (n\u0026thinsp;=\u0026thinsp;85), and \u0026lt;\u0026thinsp;40% (n\u0026thinsp;=\u0026thinsp;52). All guidewires passed through the intraplaque route. Primary patency was significantly higher in the MLA/EEMA\u0026thinsp;\u0026gt;\u0026thinsp;50% group (94.0% vs. 84.2% vs. 73.3%, log-rank \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005). Specifically, for dissection angles\u0026thinsp;\u0026gt;\u0026thinsp;60\u0026deg;, patency was markedly better in the MLA/EEMA\u0026thinsp;\u0026gt;\u0026thinsp;50% group (93.3% vs. 75.0% vs. 55.6%, log-rank \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.03). Dissection angles\u0026thinsp;\u0026lt;\u0026thinsp;60\u0026deg; showed no significant patency differences (93.9% vs. 88.0% vs. 84.2%, log-rank \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.14).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThe MLA/EEMA ratio and the degree of dissection angle may be predictors of primary patency following DCB angioplasty. These findings suggest that optimized vessel preparation strategies can effectively mitigate the adverse clinical impact of dissection.\u003c/p\u003e","manuscriptTitle":"Predictors of Restenosis After Drug-Coated Balloon Angioplasty for Femoropopliteal Chronic Occlusion Lesions","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-10 09:40:57","doi":"10.21203/rs.3.rs-7511977/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-09-11T04:56:49+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-03T12:51:53+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-03T08:17:27+00:00","index":"","fulltext":""},{"type":"submitted","content":"CVIR Endovascular","date":"2025-09-01T20:36:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"cvir-endovascular","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cire","sideBox":"Learn more about [CVIR Endovascular](https://www.springer.com/journal/42155)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/cire/default.aspx","title":"CVIR Endovascular","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"e6ffc025-1282-48a5-9e0e-6a81e98dfdb4","owner":[],"postedDate":"September 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-03T16:08:58+00:00","versionOfRecord":{"articleIdentity":"rs-7511977","link":"https://doi.org/10.1186/s42155-025-00612-4","journal":{"identity":"cvir-endovascular","isVorOnly":false,"title":"CVIR Endovascular"},"publishedOn":"2025-10-28 15:57:55","publishedOnDateReadable":"October 28th, 2025"},"versionCreatedAt":"2025-09-10 09:40:57","video":"","vorDoi":"10.1186/s42155-025-00612-4","vorDoiUrl":"https://doi.org/10.1186/s42155-025-00612-4","workflowStages":[]},"version":"v1","identity":"rs-7511977","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7511977","identity":"rs-7511977","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}