Treating CLI During COVID-19 Webinar Presented by CLI Global Society Board Members

CLIGLOBALThe Official Publication of the Critical Limb Ischemia Global Society Treating CLI During COVID-19 Webinar Presented by CLI Global Society Board Members

LI Global Society President, Dr. Dr. van den Berg and other panelists Barry Katzen, from Miami, recently reported an anecdotal increase in ampu- Cmoderated an interactive panel dis- tation over the last weeks due to patients cussion with all nine Board Members of not seeking treatment for revasculariza- the CLI Global Society. Their discussion tion in a timely manner out of fear of on treating critical limb ischemia during contracting the COVID-19 virus. The COVID-19 was attended by 350 individu- panelists discussed how they would have als globally from five continents. proceeded with patient treatment at their Dr. Jos van den Berg started off the dis- respective institutions. cussion with a case of a patient who had Dr. Andrew Holden, from New presented to his institution in Lugano, Zealand, shared that his institution does Switzerland one day prior. A 70-year-old have the ability to test. However, such male with a history of diabetes, obesity, a case with no history of travel, known and CLI presented with ulceration of the exposure, and respiratory symptoms left forefoot with ischemia. His symptoms would be revascularized without testing had been present for several weeks but he and standard personal protective equip- had been avoiding a visit to the hospi- ment (PPE) would be utilized for staff tal outpatient clinic due to fear of the and the patient would be masked. With COVID-19 virus infection. The patient the presence of a fever, they would test did present with a fever, but no known and wait 6 hours for results prior to re- exposure or respiratory symptoms. The vascularization. Professor Thomas Zeller, fever was assumed to be attributed to from Germany, said his institution would the infected wound. The patient did have take an approach similar to the one Dr. sensory deficit. Following a negative Holden described. COVID-19 test the patient was revascu- Dr. Robert Lookstein, from New York larized immediately. CT angiography was City, reported that his institution would waived due to a GFR of 27. Continued on page 16

CLI in Europe: Are There Lessons to Be Learned? Jos C. van den Berg, MD, PhD Ospedale Regionale di Lugano, sede Civico, Lugano; University of Bern, Switzerland; Board Member, CLI Global Society

CLI IS UNDERDIAGNOSED, disease. A more alarming statistic is that prevalence by 25%.7 Given these factors, it Classification Categories 4, 5, and 6, re- UNDERTREATED, AND DEADLY more than 50% of amputations occur can be estimated that between 1 million spectively.8 When an individual first re- Critical limb ischemia (CLI) is an un- without any prior vascular intervention and 3 million Americans have CLI.1 ceives a diagnosis of CLI, the mortality derdiagnosed and undertreated deadly in the year prior.4 Adding to the poor prognosis after di- risk is 24% over 1 year and 60% over 5 disease that requires proper diagnos- Efforts to estimate the true prevalence agnosis of CLI, patients with this disease years.9 Fewer diseases connote a higher tic imaging and increased awareness. of CLI in population studies are challeng- remain underserved with regard to diag- mortality rate. Among 22 different types Between 2000 and 2010, the world’s ing because the CLI diagnosis is clinically nostic evaluation, medical therapy, and of malignancy, only six have a 5-year population increased by 12.6%, and the established by a constellation of lower ex- utilization of revascularization.1 mortality rate higher than that of CLI.10 prevalence of peripheral arterial disease tremity features, including ischemic rest A study by the CLI Global Society (PAD) has increased twice as much over pain and non-healing ischemic wounds or NATURAL HISTORY OF CLI showed that mortality rates at 4 years this period.1 In the United States (US) gangrene, and requires the objective mea- A recent publication by Conte et al differed by Rutherford Class presen- and the European Union (EU), more surement of ankle or toe pressures. Few in the Journal of Vascular Surgery shows tation with 41% (Rutherford 4), 55% than 3.8 million patients suffer from CLI2 prior population-based studies have used that 12-month outcomes of patients (Rutherford 5), and 68% (Rutherford 6), and this number is expected to increase such symptom- and examination-based diagnosed with CLI are poor with a whereas major amputation rates at 4 years by 23% over the next 10 years.3 These clinical criteria to define CLI incidence 22% mortality rate and a 22% amputa- were 6% (Rutherford 4), 9% (Rutherford alarming statistics can be attributed to an or prevalence.5,6 Validation studies sug- tion rate. Amputation rates at 4 years as 5), and 30% (Rutherford 6).9 Overall, the explosion in the diagnosis of diabetes and gest that use of administrative codes for stratified by Rutherford classification are high incidence of CLI in combination decreasing mortality from cardiovascular CLI diagnosis may underestimate the true 12.1%, 35.3%, and 67.3% for Rutherford Continued on page 14

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Aortic | Peripheral | endoVenous Orders UC201903644EN © 2019 Medtronic. All 3033 Campus Drive, N550 Tel: +1.763.514.8510 rights reserved. Medtronic, Medtronic logo Plymouth, MN 55441 Toll free: +1.800.716.6700 and Further, Together are trademarks of USA Fax: +1.877.697.4841 Medtronic. All other brands are trademarks Email: [email protected] of a Medtronic company. 02/19 24-hour Technical Support Toll free: +1.800.328.2518 CardioVascular LifeLine Customer Support medtronic.com/hawkoneGlobal Tel: +1.763.526.7890 Toll free: +1.877.526.7890 CLIGLOBAL 3 Treatment of Calcified Common and EDITORIAL J.A. MUSTAPHA, MD, FACC, FSCAI Clinical Editor Deep Femoral Arteries Advanced Cardiac & Vascular Centers for Amputation Prevention Grand Rapids, MI Michael S. Lee, MD, FACC, FSCAI Clinical Associate Professor of Medicine UCLA Medical Center, Los Angeles, California Michigan State University COM, East Lansing, MI

ercutaneous vascular interven- Carson McGarrity, Publisher Carmen Heaney, Executive Editor tion (PVI) is a safe and effec- Rebecca Kapur, Managing Editor tive treatment option for symp- P Percutaneous vascular intervention of the Vic Geanopulos, Creative Director tomatic peripheral artery disease. The Elizabeth Vasil, Graphic Production ideal treatment strategy for common Manager femoral artery (CFA) disease is contro- deep femoral artery is uncommonly performed versial. Common femoral endarterecto- EDITORIAL CORRESPONDENCE: my (CFE) has been considered the stan- because angiographic complications may lead Laurie Gustafson, Executive Editor dard of care for over half a century given HMP / [email protected] to critical limb ischemia if it is the last remaining 70 East Swedesford Road, Suite 100 that the CFA is easily accessible surgical- Malvern, PA ly, technically feasible, and provides du- rable patency.1 However, CFE may not conduit to the lower limb. be a good option in some patients, es- SCIENTIFIC ADVISORY BOARD pecially if they have multiple comorbidities or are elderly.2 A large registry from GEORGE ADAMS, MD the National Surgical Quality Improve- territory to treat with PVI. Compared follow-up, there were no differences in Garner, NC ment Program database reported a 30- with CFE, PVI also provides the abil- sustained clinical improvement and the VICKIE R. DRIVER, DPM, MS day morbidity and mortality rate of 15%, ity to revascularize other vascular beds rates of primary patency, target lesion Boston, MA including a mortality rate of 3.4%.2 Sur- including the iliac and superficial femo- revascularization, and target extremity gery is also associated with infection and ral arteries. PVI of the CFA can be per- revascularization. LAWRENCE GARCIA, MD Boston, MA paresthesia. Furthermore, CFA disease formed via the radial or brachial artery There are several aspects of the CFA is commonly accompanied by involve- because of the proximal location of the which increase the technical complex- PHILIP P. GOODNEY, MD ment of the iliac or superficial femoral CFA, which decreases the risk of vascu- ity of PVI. Osteoid metaplasia, a mature Lebanon, NH arteries which are not revascularizable lar access complications and bleeding. In bone structure, was commonly observed ANDREW HOLDEN, MD during CFE. PVI represents an alterna- the TECCO trial, the stent group pro- in CFA disease.4 Severe calcification of Auckland, New Zealand tive for patients who do not want sur- vided lower rates of 30-day morbidity the CFA decreases the acute procedural gery for various reasons, including per- and mortality compared with the sur- success rate. Balloon and stent catheters MICHAEL R. JAFF, DO Newton, MA sonal preference or those who are poor gery group in patients with CFA dis- may not traverse severely calcified lesions. candidates for surgery. PVI of the CFA ease (12.5% vs. 26%, odds ratio: 2.5; 95% Calcified lesions are also difficult to fully BARRY T. KATZEN, MD is minimally invasive, non-surgical, and confidence interval: 0.9–6.6; P=.05).3 dilate and may require high pressure bal- Miami, FL can be performed on an outpatient ba- The length of stay was also lower in the loon inflations, which increase the risk ROBERT LOOKSTEIN, MD sis with same-day discharge. In contrast, stent group (3.2 ± 2.9 days vs. 6.3 ± 3 of dissection, slow flow, and perforation. New York, NY CFE often requires at least an over- days; P<.0001). Delayed wound healing Dissection of the CFA may require stent- night hospital stay. The large diameter of was more commonly observed in the ing, which is undesirable at a flexion point D. CHRIS METZGER, MD Kingsport, TN the CFA makes it an appealing vascular surgery group (16.4% vs. 0%). At 2-year Continued on page 17 RICHARD F. NEVILLE, MD Fairfax, VA CONSTANTINO S. PEÑA, MD TABLE OF CONTENTS © 2020, Critical Limb Ischemia Global, Miami, FL LLC (CLIG). All rights reserved. Repro- FADI A. SAAB, MD duction in whole or in part prohibited. Grand Rapids, MI Treating CLI During COVID-19 ...... cover Opinions expressed by authors, con- tributors, and advertisers are their own ANDREJ SCHMIDT, MD CLI in Europe: Are There Lessons to be Learned? ..... cover and not necessarily those of Critical Leipzig, Germany Limb Ischemia Global or the editorial RAMON VARCOE, MBBS, MS Treatment of Calcified Common and Deep Femoral staff. Critical Limb Ischemia Global is Sydney, Australia not responsible for accuracy of dosag- Arteries ...... 3 FRANK J. VEITH, MD es given in articles printed herein. The New York, NY SAVAL Update: Overcoming Recoil and Restenosis in the appearance of advertisements in this journal is not a warranty, endorsement JOS VAN DEN BERG, MD, PhD Treatment of Complex Tibial Disease ...... 4 or approval of the products or services Lugano, Switzerland advertised or of their effectiveness, Utilization of Tibio-Pedal Artery Minimally Invasive THOMAS ZELLER, MD quality or safety. Critical Limb Ischemia Bad Krozingen, Germany Approach to Treat Complex Below Knee Disease in a Global disclaims responsibility for any High Transfemoral Risk Patient ...... 6 injury to persons or property resulting from any ideas or products referred to Published in collaboration with Update on the STAND trial including the European in the articles or advertisements. Experience ...... 10 Content may not be reproduced in any form without written permission. Understanding the Tibial-Pedal Arterial Anatomy: Contact [email protected] Editor’s note: Articles in this Practical Points for Current Clinical Presentations ...... 12 for rights and permission. supplement to Cath Lab Digest did not undergo peer review.

June 2020 4 CLIGLOBAL SAVAL Update: Overcoming Recoil and Restenosis in the Treatment of Complex Tibial Disease

Patrick J. Geraghty, MD Vascular Surgery Section, Division of General Surgery, Washington University School of Medicine, St. Louis, Missouri

can rapidly produce a critical resteno- Table 1. Patient Eligibility for SAVAL* sis. Drug-coated balloon angioplasty in the infrapopliteal vessels has not shown •Chronic, symptomatic lower limb ischemia (Rutherford categories 4 or 5) consistent benefit across the larger ran- •Stenotic, restenotic, or occlusive target lesion(s) in the tibioperoneal domized trials.8-11 Multiple studies have trunk, anterior tibial, posterior tibial, and/or peroneal artery(ies) suggested that the off-label use of drug- •Stenosis that is ≥ 70% (based upon visual angiographic assessment) eluting coronary stents in short, proxi- •Total target lesion length ≤ 140mm. mal tibial lesions provides superior patency.12-15 However, the applicability of *Patient must have all 4 symptoms for trial eligibility. these highly selected trial populations to the more extensive tibial disease pat- The first phase of the study is a random- terns treated in everyday CLTI practice ized controlled trial (RCT) with a 2:1 ran- is questionable. It is clear that the BTK domization of subjects to SAVAL DES and toolbox would greatly benefit from the PTA, respectively (Table 1). The first phase availability of a crush-resistant, resteno- has a target enrollment of approximately sis-inhibiting scaffolding that is suitable 201 patients globally. The trial will include for deployment throughout the tibial up to 50 study sites across the United vasculature. States, Europe, and Japan. The primary The SAVAL drug-eluting stent (DES) endpoint for the first phase of SAVAL is system (SAVAL™ DES BTK, Boston primary patency of the DES in compari- Patrick J. Geraghty, MD Scientific Corp.) was developed to address son to PTA at 6-months post-procedure. Figure 1. The DES BTK Vascular the aforementioned BTK treatment gaps. In Patency assessments will be performed Stent is a laser-cut, self-expanding nitinol stent coated with an inner the SAVAL clinical trial (NCT03551496), at 1-, 6-, 12-, 24-, and 36-months post- PBMA primer layer and an outer n patients with chronic limb-threat- the primary objective is to demonstrate that procedure using duplex ultrasound. The Paclitaxel/PVDF-HFP active layer. ening ischemia (CLTI), the overarch- the SAVAL DES has a superior patency rate primary safety endpoint is major adverse Image provided courtesy of Boston Scientific. ing goal of treatment is successful re- and acceptable safety in BTK arteries com- events (MAEs) through 6-months post- © 2015 Boston Scientific Corporation or its I affiliates. All rights reserved. vascularization of the endangered limb. pared to PTA. Secondary objectives are the procedure (non-inferiority comparison Prompt restoration of adequate limb collection of additional data on limb salvage between study arms). MAEs are defined perfusion decreases the risk of amputa- and quality of life for patients participating as above-ankle amputation of the index tion and maximizes the patient’s qual- in this study. limb, major re-intervention, and/or 30- WHAT MAKES THE SAVAL TRIAL ity of life by resolving ischemic rest day peri-procedural all-cause mortality (a UNIQUE? pain and allowing healing of ischemic SAVAL DES OVERVIEW combined endpoint also known as “major The SAVAL clinical trial is the only wounds.1,2 Surgical bypass and endo- The SAVAL DES is a laser-cut, self-ex- adverse limb events and peri-procedural large study investigating a purpose- vascular revascularization (percutaneous panding nitinol stent that was purpose- death,” or MALE-POD). built, self-expanding, sustained-release transluminal angioplasty, PTA) are the built for BTK use (Figure 1). The SAVAL The second phase of the SAVAL study paclitaxel BTK DES. It is the first study primary modes of treatment for CLTI. DES system comprises three parts: the is a single-armed study to collect ongoing of peripheral vascular intervention Selection of the optimal revasculariza- stent, its coating, and the delivery sys- safety and effectiveness data. The second granted the FDA Breakthrough Devices tion method was examined in the BA- tem. Much like the ELUVIA drug- phase aims to treat 100 additional patients Program designation (formerly the SIL trial, and remains under study in eluting vascular stent system (ELUVIA™ with the DES BTK Vascular Stent System, Expedited Access Pathway program). the current BEST-CLI trial.3-7 The re- DES, Boston Scientific Corp.), which is which will include an expanded range The randomized study design will pro- cently published Global Vascular Guide- indicated for treatment of femoropopli- of stent sizes. The execution of the sec- vide a rigorous comparison of this novel lines offer a surgical perspective on risk teal disease, the SAVAL coating contains ond phase is contingent upon effective- BTK device to the current standard of stratification and high-yield application a polymer in addition to the drug itself ness demonstrated in the first phase. In treatment (PTA). Of note, patient re- of surgical bypass.2 However, as opera- (PBMA/PVDF:HFP-Paclitaxel). This the second phase of SAVAL, the primary cruitment for SAVAL was designed to tor comfort with complex endovascular combination provides sustained release safety endpoint is MAE rate at 12-months be international from the outset, with a interventions has continued to increase of paclitaxel after stent deployment, post-procedure, with continuing paten- goal of enrolling patients in the United over time, the use of endovascular inter- with a dose of 0.236µg of paclitaxel per cy-based assessments planned at 1-, 6-, States, Japan, and Europe. n vention for CLTI has predictably con- square millimeter of stent surface area. 12-, 24-, and 36-months post-procedure tinued to grow. The first part of the SAVAL trial tests using duplex ultrasound. Study Status: The SAVAL trial is actively enroll- Although CLTI is a predominantly only one stent diameter and length (3.5- ing subjects in its first phase. multilevel disease process, the increasing mm diameter, 80-mm length) to target PLANNED STATISTICAL incidence of diabetes mellitus tempo- a reference vessel diameter of 2.5 mm ANALYSES Acknowledgement: I thank Alexandra J. rally corresponds to a notable increase in to 3.25 mm. It is anticipated that addi- Briefly, analyses will utilize an “adap- Greenberg-Worisek, PhD, MPH, (Boston the need for complex below-the-knee tional stent diameters and lengths will be tive sequential testing hypotheses strate- Scientific) for providing medical writing (BTK) revascularization procedures. added to the second phase of the SAVAL gy.” Specifically, there is a planned interim assistance. Angioplasty remains the gold standard trial as additional safety and efficacy data analysis when a minimum of 70% of tar- for endovascular BTK intervention, but are gathered. get enrollment of phase one reaches the Disclosure: Dr. Geraghty reports Consulting/ clearly faces intra-procedural and post- 6-month post-procedure mark, with an Advisory Board: BSCI, BD/Bard; Equity Holder: procedural shortcomings in achieving SAVAL STUDY DESIGN adjusted Type I error for the interim and Euphrates Vascular. and maintaining optimal patency. In The SAVAL trial is a two-phase study final analyses. For the second phase, anal- the smaller caliber BTK arteries, even comparing patency and safety of the yses will be conducted when all subjects modest recoil or post-angioplasty in- SAVAL DES compared with PTA in the (pooled from both phases) have reached Continued on page 18 growth of intimal hyperplastic tissue treatment of infrapopliteal arteries. the 12-month post-procedure mark.

June 2020 Downsize Your Access Site Profile

The Halo One™ Thin-Walled Guiding Sheath reduces arteriotomy The Thin-Walled Sheath Design size compared to standard peripheral guiding sheaths of the same 6F 7F French size, which can help to minimize access site complications.1 A unique size offering makes Halo One™ Thin-Walled Guiding Sheath the only thin-walled guiding sheath with lengths suitable for distal 5F 5F peripheral interventions.2

™ Halo One™ Standard 5F Halo One Thin-Walled Guiding Sheath Guiding Sheath Thin-Walled Guiding Sheath Not drawn to scale. For illustrative purposes only.

1 Ortiz, Daniel, et al. “Access site complications after peripheral vascular interventions: incidence, predictors, and outcomes.” Circulation: Cardiovascular Interventions 7.6 (2014): 821-828. 2 Shaft lengths of 45, 70, and 90 cm are available in 4F and 5F sizes only. As of April 2020. The Halo One™ Thin-Walled Guiding Sheath is indicated for use in peripheral arterial and venous procedures requiring percutaneous introduction of intravascular devices. The Halo One™ Thin-Walled Guiding Sheath is NOT indicated for use in the neurovasculature or the coronary vasculature. Please consult product labels and instructions for use for indications, contraindications, hazards, warnings and precautions. © 2020 BD. BD, the BD logo, and Halo One are property of Becton, Dickinson and Company or its affiliates. Illustrations by Mike Austin. All Rights Reserved. Bard Peripheral Vascular, Inc. | www.bardpv.com | 1 800 321 4254 | 1625 W. 3rd Street Tempe, AZ 85281 BD-12896 6 CLIGLOBAL Utilization of Tibio-Pedal Artery Minimally Invasive Approach to Treat Complex Below Knee Disease in a High Transfemoral Risk Patient Zola N’Dandu, MD, and Jonathan Bonilla, MD John Ochsner Heart and Vascular Institute, Ochsner Medical Center-Kenner, Kenner, Louisiana

Zola N’Dandu, MD

Figure 1. Diagnostic angiogram: ATA CTO, patent PTA, patent PER, and patent LPA. ATA = anterior tibial artery; CTO = chronic total occlusion; PTA = posterior tibial artery; PER = peroneal; LPA = lateral plantar artery.

ith the evolution of endo- angiogram revealed adequate inflow with vascular techniques, histori- patent aorto-iliac, common femoral, su- Wcally untreated patients have perficial femoral, profunda, and popliteal options. Tibio-pedal artery minimal- vessels. Distally he had a chronically oc- ly invasive (TAMI) approach is safe and cluded (CTO) right anterior tibial (ATA) feasible when avoiding transfemoral ac- with a hibernating dorsalis pedis artery cess complications.1-3 (DPA), which faintly filled from a pero- Jonathan Bonilla, MD neal (PER) collateral, 90% tibial peroneal CASE REPORT trunk (TPT) stenosis, multiple 75% le- A 66-year-old male with a past medical sions in the proximal and mid posterior history of hypertension, hyperlipidemia, tibial artery (PTA), and a patent lateral insulin-dependent diabetes mellitus Type plantar artery (LPA) (Figure 1). Anticipating a high 2 for more than 20 years, coronary artery Anticipating a high risk of complica- disease previously treated with multives- tions related to transfemoral access, we risk of complications sel percutaneous coronary intervention decided to proceed with TAMI approach (PCI), ischemic cardiomyopathy with with transradial guidance. A 4- to 5-Fr related to transfemoral ejection fraction of 35%, morbid obesity Glidesheath Slender (GSS) (Terumo with body mass index (BMI) of 52, and Medical) was inserted in the right radial access, we decided sleep apnea presenting with chronic limb artery for visualization of the proximal threatening ischemia (CLTI), presented vessels. We placed a 2.9-Fr Cook ped- to proceed with with necrotizing fasciitis requiring an ur- al (Cook Medical) sheath in the ATA gent debridement for infection control. and advanced a 0.018-inch CXI (Cook Figure 2. Retrograde 2.9 Fr ATA TAMI approach with His non-invasive vascular workup in- Medical) support catheter over a 0.018- and 4-5 Fr PTA sheaths. ATA = cluded an abnormal ankle brachial index inch Command ST (Abbott Vascularl) anterior tibial artery; PTA = posterior tibial artery. transradial guidance. (ABI), an abnormal arterial ultrasound, wire. The CXI catheter and wire were and tissue oximetry. advanced through the course of the ATA He had a right transradial aortogram intraluminally except for the ostium of the Continued on page 8 with selective right leg angiogram. His ATA where the wire entered a subintimal

June 2020

8 CLIGLOBAL A B C D N’DANDU from page 6

space. Thereafter, we gained access in the right PT with a 4- to 5-Fr GSS sheath to serve as an antegrade access to cross the ATA CTO (Figure 2). A 0.018-inch CXI support catheter was telescoped within a 4-Fr Berenstein (Boston Scientific) catheter with a 0.018-inch Command wire advanced into the proximal ATA (Figure 3). The antegrade equipment was advanced into the distal ATA. The retrograde CXI catheter was pulled back in the distal AT where the antegrade wire was inserted for externalization. Subsequently the antegrade CXI catheter was exter- nalized through the retrograde 2.9-Fr sheath placed in the distal ATA (Figure 4). The 0.018-inch Command wire was exchanged for a 0.014-inch ViperWire (Cardiovascular Systems, Inc.) guidewire to perform atherectomy using a 1.5 mm Classic CSI Diamondback 360 catheter in the PTA, TPT, and ATA (Figure 5). Thereafter, based on extra vascular ultrasound (EVUS) measurements, we performed balloon angioplasty of proxi- Figure 3. Arrow (A) retrograde ATA access, (B) retrograde wire looped at ATA ostium, (C) retrograde PT access, (D) retrograde mal DPA, ATA, and PTA with a 3.5- x PTA crossed into proximal ATA. PT = posterior tibial; PTA = posterior tibial artery; ATA = anterior tibial artery. 300-mm balloon (Ultraverse BD Bard), and TPT with a 4.0- x 60-mm Lutonix

A B A B

Figure 4. Oval (A) antegrade and retrograde wires in ATA and arrow (B) externalization of antegrade wire through the retrograde ATA access. ATA = anterior tibial artery.

With the evolution of endovascular techniques, historically untreated patients have options. Tibio- pedal artery minimally invasive (TAMI) approach is safe and feasible when avoiding transfemoral access complications. Figure 5. Atherectomy of ATA through PTA access with 1.5 Classic CSI catheter. ATA = anterior tibial artery; PTA = posterior tibial artery; CSI = Cardiovascular Systems, Inc.

June 2020 CLIGLOBAL 9 A B

Figure 9. TAMI with a 5-6 Fr GSS and a distal 2.9 Fr sheath inserted at the end of the case for balloon tamponade of the 5-6 Fr sheath with 3.0 mm Advance Micro (Cook) balloon. GSS = Glidesheath Slender (Terumo Medical).

To reduce the risk of access-related complications,

A B C we usually perform balloon tamponade with 2.5- or 3.0-mm Advance Micro 14 2.5-Fr balloon through Figure 6. Angioplasty of ATA, PTA, and TPT. ATA = anterior tibial artery; PTA = posterior tibial artery; TPT = tibial peroneal trunk a distal 2.9-Fr sheath which can safely be closed with minimal manual pressure. A B DCB (BD Bard) with an excellent result complications related to transfemoral ac- (Figure 6). cess. In other cases, we used up to 5 to A 3.0- x 80-mm Advance Micro 14 2.5- 6 and 6 to 7 GSS sheaths. To reduce the Fr (Cook Medical) balloon was inserted risk of access-related complications, we through the retrograde ATA 2.9-Fr sheath usually perform balloon tamponade with over the ViperWire guidewire which was 2.5- or 3.0-mm Advance Micro 14 2.5- exchanged for a 0.014-inch Fielder XT Fr (Cook) balloon through a distal 2.9-Fr (Asahi Intecc) and advanced distally to the sheath which can safely be closed with 4- to 5-Fr GSS PTA access for intraarterial minimal manual pressure (Figure 9). We balloon tamponade to obtain hemostasis always utilize a hockey stick ultrasound (Figure 7). Finally, the retrograde 2.9 Fr probe to obtain access. We maintain an ATA sheath was removed, and hemostasis ACT greater than 250 seconds during the was achieved with manual pressure (Figure case. We inject between 200 or 400 mcg 8). He tolerated the procedure well and of intra-arterial nitroglycerin for vasodi- ambulated an hour later. He underwent lation and repeat the same process every additional debridement and placement of thirty minutes. n a wound vac. Figure 7. (A) Short arrow points to PTA access balloon tamponade, long arrow is The TAMI approach has been well Reprinted from Vascular Disease Management pointing at Fielder XT. (B) Successful hemostasis. documented. It can be utilized as an al- 2020; May, Vol. 17(5): E92-E94. ternative in patients with high risk of Disclosure: None.

A B C Dr. N’Dandhu can be reached via email at [email protected]. Dr. Bonilla can be reached via email at [email protected], and Dr. Paul is available at [email protected]

REFERENCES 1. Mustapha JA, Saab F, McGoff TN, et al. Tibiopedal arterial minimally invasive retrograde revascularization (TAMI) in patients with peripheral arterial disease and critical limb ischemia. On behalf of the Peripheral Registry of Endovascular Clinical Outcomes (PRIME). Catheter Cardiovasc Interv. 2020;95(3):447- 454. Epub 2019 Dec 13. 2. Mustapha JA, Saab F, McGoff T, et al. Tibio-pedal arterial minimally invasive retrograde revascularization in patients with advanced peripheral vascular disease: the TAMI technique, original case series. Catheter Cardiovasc Interv. 2014;83:987-994. 3. Welling RHA, Bakker OJ, Scheinert D, et al. Below- the-knee retrograde access for peripheral interventions: a systematic review. J Endovasc Ther 2018;25:345–352.

Figure 8. Final result revealed 3-vessel run-off with an intact plantar loop.

June 2020 10 CLIGLOBAL The STAND Trial: How the MicroStent® Attempts to Break Through Barriers in Below the Knee CLI Omosalewa Adenikinju, MD; Michael Patel, MD; Adam Zybulewski, MD; Brandon Olivieri, MD; and Robert E. Beasley, MD

treatment modalities, which are sometimes approach is as efficacious and less expen- used as bailout options in limb salvage cases, sive than a surgery-first strategy for the do present challenges. treatment of infrainguinal disease in CLI.9 Despite angioplasty after optimal nominal Subsequent studies, such as the meta- balloon diameter selection, Baumann et al4 analysis by Caradu et al,10 demonstrated state that up to 97% of cases have a significant no significant advantage in off-label use amount of vessel recoil in complex BTK of balloon-expandable bare metal stents lesions, thus only temporizing the luminal versus PTA in patency or wound healing, gain and inline flow achieved shortly after but highlighted good results with self-ex- procedure completion. It is also well es- panding stents for PTA bailout. However, tablished that the microtrauma exhibited no direct comparison was made to PTA by plaque during angioplasty can lead to in that analysis. non-flow and flow-limiting dissections The randomized YUKON-BTX and in approximately 20% to 30% of cases.5-7 DESTINY trials have demonstrated higher Omosalewa Adenikinju, MD Michael Patel, MD Dissections often go untreated as many are rates of freedom from target lesion revas- underreported or missed, especially in the cularization (TLR) when comparing bare absence of intravascular ultrasound (IVUS). metal and drug-eluting stents BTK, but a These tend to become a nidus for restenosis clear clinical benefit has yet to be shown.11 or occlusion.5-7 There are conflicting conclusions on im- Atherectomy devices, including laser and provement in Rutherford class, a query orbital atherectomy, can decrease plaque on the economic benefit of drug-eluting burden in tibial vessels. However, their stents, and no significant difference in ma- utility can be limited to vessel size com- jor amputations or survival has yet to be patibility and true lumen use depending demonstrated between bare metal stents upon the debulking method chosen. Even and drug-eluting stents.12-14 then, these therapies may need adjunctive Thus, in the U.S., use of BTK stenting therapy from percutaneous transluminal has traditionally been reserved to combat angioplasty (PTA) or stenting. recoil and dissections in complex CLI cases, The use of off-label drug-eluting coro- especially in patients that are poor surgical nary stents BTK has been employed in bypass candidates.10 Although some of the Adam Zybulewski, MD Brandon Olivieri, MD complex limb salvage cases for years. trials that have led to such employment may Historically, size compatibility and drug- have been limited by statistical power and eluting technology made this a viable op- short-term assessments, their findings may The goal of CLI treatment is direct: tion to improve and maintain inflow in also be reflective of the existing technol- relieve pain, augment wound healing, the BTK vessels, with favorable outcomes ogy and comprehension of CLI (from vessel improve quality of life, and prevent am- as demonstrated in the ACHILLES trial, histology to the pathological implications putation and mortality. Unfortunately, which showed high patency rates at 1 year of this systemic disease) at that time, both comorbidities such as diabetes, renal fail- with balloon-expandable drug-eluting of which have vastly evolved. ure, tobacco smoking, heart failure, and stents in BTK vessels compared to PTA.8 The current BTK revascularization out- infection tend to accompany CLI, leading However, in lieu of the recent paclitaxel comes thus far, in addition to the paclitaxel to major amputation and subsequently, in- conundrum set forth in 2018, application conundrum, suggests that the challenges in creased mortality. of the once-prized chemotherapy agent in treating BTK disease in CLI have yet to be In order to understand the intent behind the treatment of PAD/CLI must now be met. The meta-analysis of Romiti et al15 the pivotal STAND (Clinical Evaluation of evaluated on a case-by-case basis due to demonstrated more than 90% of patency the MicroSTent PeripherAl Vascular SteNt the possible increased mortality signal. In failures and amputations occurred within in Subjects with Arterial Disease Below the addition, due to their intended use, coro- 6 months after endovascular infrapopliteal Robert E. Beasley, MD Knee) trial, it is important to comprehend nary stents are typically short (<4 cm in treatment. This timeline parallels the aver- the barriers of clinical success in below-the- length) and are typically applied only to age wound healing time seen after com- knee (BTK) revascularization. the proximal tibial vessels when feasible. plex BTK revascularization.16,17 Keeping CLI OVERVIEW Since they are balloon-expandable, these ‘20/50’ in mind, along with the poor out- Peripheral arterial disease (PAD) re- BARRIERS TO SUCCESSFUL BTK stents tend to have limited flexibility and comes described throughout this article, mains a critical, independent predictor of TREATMENT have less radial strength than self-expand- the efficacy that can flatten CLI mortality coronary artery disease, cerebrovascular BTK disease is commonly composed of ing stents, thus bringing a higher risk of is apparent by 6 months. By establishing disease, and mortality.1 A subset of PAD complex tandem, long-segmented lesions extrinsic compression. primary effectiveness and safety endpoints patients progress toward a malignant form that require complicated revascularization With the present challenges, it is im- at 6 months, the STAND trial seeks to break of disease known as critical limb ischemia techniques. Currently, there is no U.S. Food perative to use evidence-based medicine down the barriers that have held us back (CLI).2,3 Vascular specialists and other pro- and Drug Administration (FDA)-approved when forming a treatment algorithm for from successful BTK treatment. viders alike cringe when the term ‘CLI’ stent for primary treatment of BTK disease. BTK revascularization. Historically, the is used, as the numbers ‘20/50’ come to Thus, treatment of these complex, diseased BASIL trial simulated equal amputation- THE MICROMEDICAL SOLUTIONS mind: 20% of patients with CLI die within vessels has been limited to angioplasty, re- free survival at 6 months between patients MICROSTENT® 6 months, while 50% of patients die within cent atherectomy, and off-label use of undergoing PTA versus infrainguinal sa- The MicroMedical Solutions Micro- 5 years. MicroMedical is researching how drug-eluting coronary stents in the setting phenous vein bypass to an above-the- Stent® is a self-expanding nitinol stent de- to flatten this curve by changing outcomes of matched luminal diameter and previously knee or BTK arterial segment. The signed with the intent to treat BTK vessels at 6 months and beyond. revered drug-coated technology. These BASIL trial proved that an endovascular in CLI and combat the alarming amputation

June 2020 CLIGLOBAL 11 CASE EXAMPLE of freedom from occlusion, clinically driven Address for correspondence: Robert E. Beasley, TLR, and major amputation. MD, Chief of Vascular and Interventional A B C Primary safety endpoint: Freedom from Radiology and the Director of the Wound perioperative death and MALE at 30 days Healing Center at Mount Sinai Medical Center in and 6 months, respectively, based on the Miami Beach, Florida. Email: [email protected] FDA primary safety endpoint for CLI trials adopted from Conte et al.19 REFERENCES Hypothesis-tested secondary endpoints 1. Mustapha J, Saab F, Diaz-Sandoval L, et al. The Peripheral RegIstry of endovascular clinical outcoMEs (The PRIME include the reduction in size of ischemic Registry): Interim Analysis of the first 328 subjects wounds at 6 months. with critical limb ischemia. Vascular Disease Management. As mentioned previously, outcomes 2017;14(3):E55-E66. 2. Jaff MR, White CJ, Hiatt WR, et al. An update on methods success for endovascular treatment of in- for revascularization and expansion of the TASC Lesion frapopliteal lesions is largely apparent by 6 Classification to include below-the-knee arteries: a sup- months post procedure. The STAND trial’s plement to the Inter-Society Consensus for the management of peripheral arterial disease (TASC II). Vasc Med. primary endpoints are 6 months, but long- 2015;20(5):465-478. term follow-up will continue for 3 years. 3. Liistro F, Porto I, Angioli P, et al. Drug-eluting balloon The STAND trial is in the early enroll- in peripheral intervention for below the knee angioplasty evaluation (DEBATE-BTK): a randomized trial in ment phases with the first patient enrolled in diabetic patients with critical limb ischemia. Circulation. early April 2020. Figure 1 describes this case, 2013;128(6):615-621. which mirrors the high-risk demographic 4. Baumann F, Ozdoba C, Gröchenig E, Diehm N. The importance of patency in patients with critical limb ischemia Figure 1. 59-year-old patient with history of smoking, hypertension, dyslipidemia, #CLIFighters evaluate and treat to prevent undergoing endovascular revascularization for infrapop- stroke, and PAD with debilitating RC IV left lower extremity pain with ankle-brachial in- amputation and thus reduce mortality. We liteal arterial disease. Front Cardiovasc Med. 2015;7:1-7. dex indicative of moderate PAD. Digital subtraction angiography demonstrates (A) 5.1 look forward to the 30-day follow-up, doi:10.3389/fcvm.2014.00017 cm (length) target lesion in the 3 mm (diameter) tibioperoneal trunk with multiple tan- 5. Razavi MK, Mustapha JA, Miller LE. Contemporary which is pending at the time of authorship. systematic review and meta-analysis of early outcomes dem significant stenoses on angiography and IVUS (not pictured), with sluggish flow with percutaneous treatment for infrapopliteal atheroscle- ® distally. (B) Successful deployment and post dilation of a 3 x 40 mm MicroStent with HEAL REGISTRY rotic disease. J Vasc Interv Radiol. 2014;25(10):1489-1496. doi:10.1016/j.jvir.2014.06.018 post deployment length of 5.8 cm, providing adequate lesion coverage. (C) Comple- As our globe battles the challenges tion angiography demonstrates less than 10% residual stenosis with improved flow. 6. Fanelli F, Cannavale A, Corona M, et al. The brought forth by COVID-19, enrollment “DEBELLUM” — lower limb multilevel treatment with in the STAND trial has been temporarily drug eluting balloon — randomized trial: 1-year results. J Cardiovasc Surg (Torino). 2014;55(2):207-216. and death rates. With the goal of limb sal- stenting. How does this low-profile, flex- paused to ensure the safety of physicians 7. Zeller T, Baumgartner I, Scheinert D, et al. Drug-eluting vage, the stent has been tailored to meet ible, easy-to-use delivery system translate and patients. The MicroStent® is also un- balloon versus standard balloon angioplasty for infrapop- the challenges that come with diseased clinically for our patients? der investigation in Europe through the liteal arterial revascularization in critical limb ischemia: 12-month results from the IN.PACT DEEP random- tibial vessels. The woven nitinol composi- HEAL registry, which began enrollment ized trial. J Am Coll Cardiol. 2014;64(15):1568-1576. tion makes the scaffold highly conformable MICROMEDICAL SOLUTIONS in October of 2019. The HEAL registry is doi:10.1016/j.jacc.2014.06.1198 without excessive outward force. This is MICROSTENT® FEASIBILITY STUDY an open-label, all-comers registry in Italy, 8. Scheinert D, Katsanos K, Zeller T, et al. A prospective randomized multicenter comparison of balloon angio- advantageous as it allows for the following: Here we provide a brief overview of the Belgium, Germany, Netherlands, and Aus- plasty and infrapopliteal stenting with the sirolimus-eluting (1) Precise deployment. The lesion results from the feasibility study performed tria, seeking to characterize the real-world stent in patients with ischemic peripheral arterial disease: length is matched to the predicted stent in 2018. The study consisted of 15 patients use of the MicroStent®, with open inclu- 1-year results from the ACHILLES trial. J Am Coll Cardiol. 2012;60(22):2290-2295. doi:10.1016/j.jacc.2012.08.989 length upon deployment based on vessel of Rutherford classification IV-V with tib- sion and exclusion criteria. Furthermore, as 9. Adam DJ, Beard JD, Cleveland T, et al. Bypass versus angio- diameter. With help from the 3 French (Fr) ial disease. Average lesion length was 40.6 regards real-world experience, the registry plasty in severe ischaemia of the leg (BASIL): multicentre, MicroGuide® catheter, this ensures reliable mm (42.7 mm on core lab analysis), with places no parameters on adjunctive therapy, randomised controlled trial. Lancet. 2005;366:1925–1934. ® 10. Caradu C, Brizzi V, Auque H, Midy D, Ducasse E. Sense and accurate stent selection by the operator an average of 93% stenosis (74.8% on core permitting evaluation of the MicroStent and nonsense of bare metal stents below the knee. J and precise delivery. lab analysis). One hundred percent techni- in conjunction with additional treatments. Cardiovasc Surg (Torino). 2016;57(5):653-666. (2) Optimal stent opposition. The cal success (defined as stent full expansion, The primary effectiveness endpoint is pri- 11. Rastan A, Tepe G, Krankenberg H, et al. Sirolimus-eluting stents vs. bare-metal stents for treatment of focal lesions in stent adheres to varying eccentric plaque deployment without deformation, and le- mary patency at 6 months post procedure, infrapopliteal arteries: a double-blind, multi-centre, rand- morphologies as seen on IVUS, permit- sion coverage as intended) was achieved in as defined by freedom of target lesion occlu- omized clinical trial. Eur Heart J. 2011;32:2274-2281. ting luminal gain in lesions that normally all cases, based upon independent analysis sion and clinically driven TLR. The safety 12. Rastan A, Tepe G, Krankenberg H, et al. Sirolimus-eluting stents vs. bare-metal stents for treatment of focal lesions recoil after angioplasty, for example. Nota- from a core laboratory. Clinical Events endpoint is freedom from major adverse in infrapopliteal arteries: a double-blind, multi-centre, ran- bly, the integrated platinum core provides Committee and core lab-adjudicated pri- limb events. Additional enrollment and domized clinical trial. Eur Heart J. 2011;32(18):2274-2281. unequivocal visualization on follow-up mary patency was 91.7% at 30 days in de- analysis are forthcoming. 13. Bosiers M, Scheinert D, Peeters P, et al. Randomized comparison of everolimus-eluting versus bare-metal stents intra- and extravascular ultrasound. Out- vice-related analysis. The safety endpoint, a in patients with critical limb ischemia and infrapopliteal comes are enhanced with the use of IVUS, composite of freedom from major adverse CONCLUSION arterial occlusive disease. J Vasc Surg. 2012;55(2):390-398. considered “best practice” in the ongoing limb events (MALE) and freedom from As our world heals from the impacts of the doi:10.1016/j.jvs.2011.07.099 14. Benjo A, Macedo F, Aziz E, et al. TCT-164 Below-knee STAND trial. IVUS helps to characterize perioperative death at 30 days, was 100%. COVID-19 pandemic and research contin- drug eluting stents have improved patency, and symptoms the lesion in three dimensions, and evalu- At 6 months, the gold standard in order to ues, we remain enthusiastic in our view of compared to bare metal stents: a meta-analysis. J Am Coll ate flow and optimal stent apposition post ensure optimal wound healing was 90.9% how the MicroStent® will contribute to the Cardiol. 2018;60(17 Supplement):B47. doi:10.1016/j. jacc.2012.08.184 deployment. primary patency and 100% primary safety. dynamic limb salvage treatment landscape, 15. Romiti M, Albers M, Brochado-Neto FC, Durazzo AES, (3) “Gentle” luminal gain. As exces- with its goal of clinically effective change Pereira CAB, Luccia ND. Meta-analysis of infrapopliteal sive chronic outward force between the in- STAND TRIAL by 6 months. n angioplasty for chronic critical limb ischemia. J Vasc Surg. 2008;47(5):975-981.e1. doi:10.1016/j.jvs.2008.01.005 tima and stent can propagate inflammation After promising results from the initial 16. Shiraki T, Iida O, Takahara M, et al. Predictors of delayed promoting in-stent restenosis (ISR),18 es- cohort, the FDA approved the pivotal Reprinted from Vascular Disease Management wound healing after endovascular therapy of isolated infr- pecially in small-caliber arteries, this stent’s STAND trial to evaluate the MicroStent® 2020;17(5):E100-E103. apopliteal lesions underlying critical limb ischemia in patients with high prevalence of diabetes mellitus and hemo- self-expanding scaffold negates elastic recoil for primary instruction-for-use stenting dialysis. Eur J Vasc Endovasc Surg. 2015 May;49(5):565-573. with gentle outward radial resistive force to in tibial vessels. STAND is a randomized, Disclosure: Dr. Beasley reports the follow- doi: 10.1016/j.ejvs.2015.01.017. decrease the rates of ISR. multicenter, clinical study of the Micro- ing disclosures: Speaker/Trainer for Abbott 17. Okazaki J, Matsuda D, Tanaka K, et al. Analysis of wound ® healing time and wound-free period as outcomes af- Lastly, the stent comes in varying sizes to Stent device versus PTA in up to 177 pa- Vascular, BSCI (also, Medical Advisory Board), ter surgical and endovascular revascularization for criti- treat vessel diameters ranging from 2.5 to tients across 25 sites in the United States. Cardinal Health/Cordis, Cook Medical, CR cal lower limb ischemia. J Vasc Surg. 2018;67(3):817-825. 4.5 mm, and lengths from 8 to 60 mm, de- Cadaver lab training was provided to op- BARD/Becton Dickinson (also, Medical doi:10.1016/j.jvs.2017.07.122 ® 18. Ho KJ, Owens CD. Diagnosis, classification, and treatment livered on the 3 Fr MicroGuide catheter. erators. The study aims to demonstrate that Advisory Board), CSI, Endologix, Inari, of femoropopliteal artery in-stent restenosis. J Vasc Surg. Catheter delivery lengths are available in 40 the MicroStent® is superior to PTA alone Medtronic, Micro Medical Solutions, Philips/ 2017;65(2):545-557. doi:10.1016/j.jvs.2016.09.031 cm and 120 cm, permitting retrograde and in achieving and maintaining vessel patency Volcano/Spectranetics, Penumbra, Terumo/ 19. Conte MS, Geraghty PJ, Bradbury AW, et al. Suggested objective performance goals and clinical trial design for eval- antegrade deployment. These evolutions in and improved blood flow. Bolton, WL Gore. Dr. Oliveri reports that he is uating catheter-based treatment of critical limb ischemia. design aim to provide successful long-term Primary efficacy endpoint: Primary patency an unpaid speaker for Penumbra. The remain- J Vasc Surg. 2009;50(6):1462-1473.e1-e3. doi:10.1016/j. outcomes in CLI patients after primary at 6 months. Primary patency is a composite ing authors report no disclosures. jvs.2009.09.044

June 2020 12 CLIGLOBAL Understanding the Tibial-Pedal Arterial Anatomy: Practical Points for Current Clinical Presentations Vlad Adrian Alexandrescu, MD, PhD1; Arnaud Kerzmann, MD2; Ross Melvin, DO3; Augustin Limgba, MD3

1Department / Thoracic and Vascular Surgery, Princess Paola Hospital, Marche-en-Famenne, IFAC-Vivalia,Belgium; Consultant in the Cardio-Vascular and Thoracic Department, CHU Sart-Tilman Hospital, Liège, Belgium. 2Department / Thoracic and Cardio-Vascular Surgery, CHU Sart-Tilman Hospital, Liège, Belgium. 3Department / Interventional Cardiology, Cardiovascular Institute of the South, Houma, Louisiana Excerpted from VASCULAR DISEASE MANAGEMENT 2019;16(7):E179-E182.

he lower limb arterio-venous vas- anatomical features of the lower limb is the deep plantar artery. These three DP- surgical15,18 or endovascular approaches11,19 culature has a gradually tapering beneficial for the interventionist. Such dependent branches are large collaterals for revascularization procedures can be Tdistribution, with around 91% of knowledge facilitates diagnostic solutions (around 1 mm diameter) and provide a initiated. A higher frequency of long (>15 cases showing typical patterns of vascu- in various presentations of ischemic limbs, weighty local compensatory flow of > 80 cm) calcific obstructions in the segment lature and 9% with anatomical variations, as well as a better perspective of outcomes mL/min.10,12,16 of the PT appears to be more prevalent and is closely related to the muscular when planning revascularization for opti- Anatomical variations. According in diabetic and renal patients.13,17 At the components of the leg.1,2 Arterial vascu- mal tissue regeneration.6-8 to a recent meta-analysis by Kropman and ankle level, in the retro-malleolar zone, the lature of the calf and foot gathers three colleagues that included 7671 cases, atypi- PT crosses the retinaculum of the flexor main vascular bundles: the anterior, the MAIN TIBIAL TRUNKS cal calf and foot arteries were observed in muscles of the foot, a transition zone to- posterior, and the peroneal arteries. These The anterior tibial artery (AT) origi- approximately 7.9% to 10% of individu- wards the fixed plantar circulation.10,17 arteries correlate with four distinct an- nates at the interosseous membrane of als.1 High origins (at the popliteal level) This high shear-stress zone (similar to the atomical compartments in the calf, and the calf as the first principal infragenicu- of AT, or atypical tibial trifurcations, were adductor ring for the superficial femoral nine others in the foot, and are associated lar arterial branch. At this level, it reveals a reported in 5.6% to 6.2% of individuals, artery, or the extensor retinaculum for the with roughly sixteen corresponding in- constant angulation (of changing degrees while abnormal DP origins were found AT),16,17 equally inflicts local turbulence of framalleolar bundles.1-3 in individuals), “the hook.” Calcifications in 4.3% to 6% of cases.1,2,7 An anomalous flow and chronic endothelial injuries that In addition to this balanced compart- may commonly be encountered at this first dorsal metatarsal artery origin, associ- may lead to a higher prevalence of ath- mental distribution, the lower limb arte- anterior crossing point6-8 between dis- ated with atypical first toe collateral perfu- erosclerotic disease.10,13,17 After releasing its rial tree follows specific areas of tissue tinct leg compartments. This calcification sion, was described in 8.1% of individuals, medial calcaneal branch, the PT bifurcates framed in characteristic vascular modules, is thought to be due additional stiffness concomitant abnormalities of the arcu- at the plantar aspect of the foot, into the known as “angiosomes.”4 Similar to genu- and turbulences that are induced by the ate artery in 5%, and variants of plantar medial and the lateral plantar arteries. The ine muscular compartmental orientation, surrounding fibro-tendinous structures.7 arches and plantar arteries in 5%.1,2,7,12 The lateral plantar vessel represents an impor- the angiosome partition expresses topo- The AT artery courses within the anterior presence of one atypical tibial or pedal tant, large caliber (1-1.5 mm) terminal PT graphic reproducibility in humans.4-6 The compartment of the lower leg and foot presentation on one leg should alert the bifurcation that further creates the deep angiosomal branches are not indivisible, or and is associated with relatively uncompli- interventionalist to a 21% risk of encoun- plantar arch. Both foot arches share vital “terminal” ramifications of the entire arte- cated interventional and surgical access for tering similar abnormalities on the contra- compensatory flow via the deep plantar rial tree. 4,5,7 They are millimetric branches revascularization.5,11-13 lateral extremity.1,2,7 Although it is useful artery, an important trifurcation branch that further divide in smaller divisions (“fi- Interestingly, according to the remark- to acknowledge these abnormalities, these from the DP.4-6 The PT, via its medial cal- nal ramifications”), 4,5 before reaching the able anatomical description by Taylor, anatomical variants may prompt a more caneal branch, and through the medial and arteriolar level with specific, topographi- muscles in the anterior compartment of detailed local angiosomal flow evaluation, lateral plantar source arteries, provides an- cally oriented zones of tissues. From the the lower limb, and also in the dorsal foot yet only lead to small changes in wound- giosomal topographic flow for the plantar main ilio-femoral flow sources, through- are only supplied by one specific AT an- targeted revascularization.6-8 This strategy portion of the foot and toes, in addition to out the angiosome branches, and down giosome.5 This high-value information follows and adapts to every available local providing 70% of perfusion in the heel.5-7,16 to the capillaries, a harmonious “pyramid can assist in better understanding of certain collateral network, with or without un- Anatomical variations. According of gradual limb flow distribution” is cre- ischemic wound presentations in the pres- characteristic anatomical features.7 to the meta-analysis by Kropman and col- ated. 4,5 This vascular system is structured ence of stenotic AT flow and related loss Practical issues. Large DP collater- leagues, PT native variants can be found in in several levels of tapering vessels (Levels I of collaterals.5,7 It also can facilitate better als (±1 mm diameter) on the lateral side about 6.8% of individuals.1 Among these to VI)7 toward specific angiosomes.7,8 Each planning for regional revascularization. of the foot (the “lateral tarsal” or “diago- variations, PT artery hypoplastic, aplas- of these levels continuously provides co- At the ankle level and underneath the nal arteries”) connect the AT territory to tic, or high emergences were observed in ordinated and dynamic adaptations in re- extensor retinaculum of the foot, the AT the lateral plantar branches that belong to 3.3% of cases. TP dominance (absence of gional perfusion, in accordance with vari- transitions into the dorsalis pedis (DP) the posterior tibial artery (PT), in an ef- the AT artery) was documented in 1.5% of ous endogenous and exogenous factors.7-10 branch. This zone of flow towards the fective regulatory system.5-8,17 In cases of cases,1, 2 whereas atypical plantar arch and Every bifurcation becomes progressive- pedal circulation represents a second area DP thrombosis in patients with unaffected plantar arteries were seen in 5% of cases.1 ly thinner than its parent trunk.9,10 Each of increased flow turbulences and a higher diagonal vessels, healing of dorsal foot and In atypical cases, the vast majority of the arterial path progressively branches into risk of local atherosclerotic occlusive dis- anterolateral ischemic wounds can be ob- plantar vessels have a peroneal origin.1 inferior degrees of segmentation that ulti- ease along the course of the vessels.7,12 served as a result of these collateral branch- Practical issues. As mentioned for mately creates a wider cross-sectional area Both the AT and DP provide flow to es.6,8,17 Conversely, with thinner (< 1 mm) the dorsal foot and the arcuate artery (DP/ toward peripheral tissues and increases the the superficial and deep structures (DP an- and less available collaterals on the medial AT), the lateral plantar artery (PT) holds a amount of perfusion to the tissue.9,10 giosome) of the dorsal aspect of the foot, aspect of the foot (medial tarsal arteries), parallel and key role for the plantar side of It is important to note that even in the up to the toes.4-6 The AT also supplies the the same DP dysfunction seldom allows the foot. Probably among the most diffi- presence of sparse arterial anatomical vari- anterior peri-malleolar ankle perfusion.4-6 recovery of dorsomedial CLI ulcers, and cult ischemic foot lesions to treat by pure- ants (9-12%),1,2 the limb maintains steady The AT terminates at the first dorsal meta- wounds improve only via indirect, medial ly hemodynamic means are those located vascular distribution among all compart- tarsal space by dividing the arcuate artery, plantar collateral support.6,7,17 at the hallux level.6-8 The hallux and the ments, angiosomes, and their collateral an influential compensatory vessel of the The posterior tibial artery (PT) bifur- first interdigital space territories are an im- networks.1,5-7 No random flow is observed dorsal angiosome that also affects the cates the tibio-peroneal trunk (TPT),2-3 portant collateral hub of the forefoot.7,10,17 among the calf perfusion sectors, or be- entire forefoot and distal limb preserva- cm distally from the AT emergence. The This zone is a watershed area from at least tween the dorsal and the plantar territo- tion.6-8,14,15 At the same level, the DP cre- PT courses along the deep posterior two or three neighboring angiosomal ries of the foot.2,6,7 Appropriate knowledge ates the first dorsal metatarsal artery and compartment of the calf where current “source arteries.” These watershed arteries

June 2020 CLIGLOBAL 13

Practical issues. Specific forefoot and (angiosomes) of the body: experimental study and clin- hindfoot ischemic wounds or multiple ical applications. Br J Plast Surg.1987;40(2):113-141. 5. Taylor GI, Pan WR. Angiosomes of the leg: ana- CLI ulcers often reveal severe neighboring tomic study and clinical implications. Plast Reconstr collateral deprivation that originates from Surg.1998;102(3):599-616. two or three affected neighboring angio- 6. Attinger CE, Evans KK, Bulan E, Blume P, Cooper somes.6-8 In such cases, routine angiosomal P. Angiosomes of the foot and ankle and clinical implications for limb salvage: reconstruction, incisions, evaluation can be arduous to perform. and revascularization. Plast Reconstr Surg. 2006;117(7 Advanced macro and microcirculatory Suppl):261S-293S. CLI conditions perpetuate the destruction 7. Alexandrescu VA, Defraigne JO. Angiosome system of collateral and cutaneous perforators.7-9 and principle, Chapter 77: in Lanzer P. Textbook of Catheter-Based Cardiovascular Interventions. Ed. These patterns are frequently encoun- Springer. 2018;1344-1358. tered in diabetic or renal patients8,21-23,28 8. Alexandrescu VA, London V. Angiosomes: the cu- with severely distorted angiosomal land- taneous and arterial evaluation in CLI patients. marks.7,8,17,28 Clinical representation of the In: Mustapha, JA, Ed. Critical Limb Ischemia: CLI Diagnosis and Interventions. Chicago, Illinois: HMP; most impressive ischemic ulcer or necrosis 2015:71-88. zone may not always relate to the lowest 9. Schaper W. Collateral circulation: past and present. perfusion area in CLI feet.8 Irregular decay Basic Res Cardiol.2009;104(1):5-21. 7,8,17,28 10. Williams PL, Warwick R, Dyson M, et al. Angiology, of collaterals, the patchy distribution blood vessels. In: Gray’s Anatomy. 38th Ed. London: of remnant choke vessels and cutaneous Churchill Livingstone. 1996: 682-694. Figure 2. Schematic representation perforators,5,17,27 local capillary shunting 11. Mustapha JA, Diaz-Sandoval LJ, Saab F. Innovations of the main branches of the plantar by severe neuropathy,7,28 sepsis triggering in the endovascular management of critical limb foot arteries: ischemia: retrograde tibiopedal access and ad- edema, and deep compartment hyper- vanced percutaneous techniques. Curr Cardiol Rep. 1. Lateral plantar artery and plantar 7,17 Figure 1. Schematic representation pressure may all lead to substantial vari- 2017;19(8):68-70. arch. of the dorsalis pedis artery and its ations in “real-life” CLI presentations. 12. Alexandrescu VA. Angiosomes applications in Critical 2. Medial plantar artery. main branches: Parallel risk factors for tissue recovery Limb Ischemia: in search for relevance. Torino, Italy: 3. Proximal perforating arteries. Edizioni Minerva Medica. 2012. 1. Arcuate artery. 4. Distal perforating arteries. such as chronic inflammation, fibrotic 13. Toursarkissian B, D’Ayala M, Stefanidis D, et al. 2. Deep plantar artery. scars, recurrent sepsis, extended necrosis, Angiographic scoring of vascular occlusive disease in 3. First dorsalis metatarsal artery. and regional hyper-pressure syndromes, the diabetic foot: relevance to bypass graft patency and 4. Lateral tarsal (diagonal) arteries. anterior and PT arteries, respectively, in a may lead to acute thrombosis of small limb salvage. J Vasc Surg. 2002;35(3):494-500. 14. Zheng XT, Zeng RC, Huang JY, et al. The use of the 5. Medial tarsal arteries. 6-9,15-17 high-value collateral rescue network. collaterals, particularly the highly vulner- angiosome concept for treating infrapopliteal critical As an angiosomal “source arteries” pro- able interdigital and cutaneous perforator limb ischemia through interventional therapy and de- are the first dorsal metatarsal artery (DP/ vider, the peroneal trunk lends flow to a branches.7,14,17,28 Understanding these ele- termining the clinical significance of collateral vessels. AT), and the media and lateral plantar ar- more narrowed zone of the lateral heel via ments may help clinicians to better decode Ann Vasc Surg. 2016;32:41-49. 15. Rashid H, Slim H, Zayed H, et al. The impact of arte- 1,6,17 teries (PT). Critical ischemic wounds/ its lateral calcaneal artery, and also to the the real ischemic burden of each ulcer pre- rial pedal arch quality and angiosome revascularization necrosis confined to this level are often anterolateral ankle via its anterior perforat- sentation and more completely assess even- on foot tissue loss healing and infrapopliteal bypass expressions of a wider and multilevel oc- ing branch and source artery.4-6 tual wound-directed revascularization. outcome. J Vasc Surg. 2013;57(5):1219-1226. 16. Summer DS. Hemodynamics and rheology of vas- clusive disease, located upstream of the Anatomical variations. The pero- cular disease: applications to diagnosis and treatment. 6,13 pedal vessels. Necrotic lesions detected neal artery shares fewer independent ab- CONCLUSIONS In: Ascer E, Hollier LH, Strandness D Jr., Towne JB. in this foot territory frequently indicate normal distributions than those described From main ilio-femoral vascular sourc- Haimovici’s Vascular Surgery, Principles and Techniques. severe disease of the plantar and forefoot among all tibial trunks. Most cited vari- es, throughout the angiosome branches, 4th Ed. Blackwell Science Cambridge, London. 1996; 104-124. collateral web, and critical injury of more ants are associated with a high peroneal and up to the arteriolar and the capillary 17. Alexandrescu VA. Contributions of the angiosome than half of all native compensatory hallux origin from a dominant calf peroneal vasculature, there is a harmonious pyramid concept in the management of the ischemic diabetic interdigital collaterals.7,14,17 trunk in hypoplastic or aplastic PT pre- of gradual arterial limb flow distribution. foot. PhD Thesis University of Liège, Ed. Thomas & In the anterior and posterior tibial- sentations (± 3%).1,2 CLI is associated with specific infrage- Chabot. 2018: 14-55. 18. Hughes K, Domenig CM, Hamdan AD, et al. Bypass pedal arterial vasculature, specific “high Practical issues. In the CLI context, nicular patterns of arterial atherosclerotic to plantar and tarsal arteries: an acceptable approach to shear-stress” flow zones have been de- the peroneal trunk currently has fewer decay. Compensatory flow pathways are limb salvage. J Vasc Surg.2004;40(6):1149-1157. scribed. These zones seem preferentially calcifications than the AT or PT, with useful for interventionalists to understand 19. Manzi M, Palena LM. Treating calf and pedal vessel exposed to severe atherosclerosis, chronic higher technical accessibility for surgi- for eventual topographic foot reperfusion. disease: the extremes of intervention. Semin Intervent Radiol. 2014;17(3):313-319. 8,13 occlusions, and heavy calcifications. cal or endovascular techniques for limb Regardless of irregular collateral availabil- 20. Ricco JB, Gargiulo M, Stella A, et al. Impact of an- Therefore, the “flexor retinaculum” pas- salvage.13,17,22 Large-caliber anterior and ity, efficient limb revascularization must giosome- and nonangiosome-targeted peroneal by- sage (concerning the PT), the interosseous posterior communicants may provide involve direct, in-line arterial reperfusion pass on limb salvage and Healing in patients with membrane transition point (the AT), and good filling in the foot arches, although from the level of the iliac down to the chronic limb-threatening ischemia. J Vasc Surg. 2017;66(5):1479-1487. 13,16,17 also the “extensor retinaculum” (the AT), only in isolated collateral patterns. foot arches to achieve limb salvage and ad- 21. Elsayed S, Clavijo LC. Critical limb ischemia. Cardiol all represent constant challenging zones Accordingly, some authors have labeled equate wound healing. n Clin. 2015;33(1):37-47. for endovascular techniques,8,13 via ei- the PA as “the best artery to treat,” par- 22. Chin JA, Sumpio BE. New advances in limb salvage. Surg Technol Int. 2014;25:212-216. Disclosure: All authors have completed ICJME ther antegrade or retrograde passages and ticularly in the multifaceted diabetic foot 23. Faglia E, Clerici G, Caminiti M, et al. Heel ulcer and 11-13 20-22 approaches. context. Although the PA can provide disclosure forms and have reported no conficts blood flow: the importance of the angiosome concept. The peroneal artery (PA) supplies the an effective rescue supply for most CLI of interest regarding the content herein.. Int J Low Extrem Wounds. 2013;12(3):226-230. lateral compartment of the leg. The PA is Rutherford 4 presentations,20-22 its useful- 24. Neville RF, Attinger CE, Bulan EJ, Ducic I, 5-6 Thomassen M, Sidawy AN. Revascularization of a often seen as a “rescue” revascularization ness in healing Rutherford forefoot or Address for correspondence: Vlad Adrian specific angiosome for limb salvage: does the target trunk, as it shows less significant athero- hindfoot complex tissue lesions by un- Alexandrescu, MD, PhD, Department of artery matter? Ann Vasc Surg. 2009; 23(3) :367-373. sclerotic occlusive disease in the common specific indirect revascularization remains Thoracic and Vascular Surgery, Princess Paola 25. Dilaver N, Twine CP, Bosanquet DC. Direct vs indi- CLI context. Accordingly, it can support questionable.14,17,23-25 Meticulous preoper- Hospital, Marche-en-Famenne, IFAC-Vivalia, rect angiosomal revascularization of infrapopliteal arteries, an updated systematic review and meta-analysis. 15,18 current surgical or more demanding ative angiographic assessment may enable Belgium. Email: [email protected] Eur J Vasc Endovasc Surg. 2018;56(6):834-848. endovascular transcutaneous approaches11,19 us to identify and utilize every individual 26. Brochado-Neto FC, Cury MV, Bonadiman SS, et al. for reperfusion. Despite traveling in the peroneal flow distribution and collateral REFERENCES Vein bypass to branches of pedal arteries. J Vasc Surg. deep posterior compartment of the calf, partition when planning wound-targeted 1. Kropman RH, Kiela G, Moll FL, de Vries JP. Variations 2012;55(3):746-752. 27. Rozen WM, Ashton MW, Le Roux CM, Pan WR, the PA ends superficially by its lateral cal- revascularization.7,13,17 in the anatomy of the popliteal artery and its side branches. Vasc Endovasc Surg. 2011;45(6): 536-540. Corlett RJ. The perforator angiosome: a new concept caneal branch, a “terminal-type” branch 2. Yamada T, Gloviczki P, Bower TC, Naessens JM, in the design of deep inferior epigastric artery per- that provides 30% of the heel perfusion.10,16 For further discussion, including Carmichael SW.Variations of the arterial anatomy of forator flaps for breast reconstruction. Microsurgery. From a clinical perspective, the peroneal pedal arches, angiosomes of the the foot. Am J Surg.1993;166(2):130-135. 2010;30(1):1-7. lower leg, and variations of the isch- 3. Alexandrescu VA, Van Espen D. Threatening inferior 28. O’Neal LW. Surgical pathology of the foot and clini- artery provides two important collateral limb ischemia: when to consider fasciotomy and what copathologic correlations. In: Bowker JH, Pfeifer MA. emic foot, see VASCULAR DISEASE branches at the ankle level: the anterior principles to apply? ISRN Vasc Med. 2014;21:1-9. Levin and O’Neal’s The Diabetic Foot. 7th Ed. Mosby and the posterior communicants that join MANAGEMENT 2019;16(7):E179-E182. 4. Taylor GI, Palmer JH. The vascular territories Elsevier, Philadelphia. 2007: 367-401.

June 2020 14 CLIGLOBAL

Figure 1. Lower extremity amputation rates in diabetes. OECD 2000–2001.

from 10.8 to 7.5 per 100,000 (-30.6%). Additionally, a mean reduction of major amputations in people with diabetes from 182.9 to 128.3 per 100,000 (-29.8%) was seen. Interestingly, minor amputations remained stable over the study period. The implementation of standardized definitions, necessary to increase the comparability of multina- tional data, highlighted remarkable differences between countries. Therefore, these results can help identify and share best practices effectively on a global scale (Figures 2 and 3).12 An overview of data available from various European countries can be found below.

CLI SITUATION IN BELGIUM In a nationwide study of 5,438 individuals provided by the Belgian national health insurance funds, cov- ering more than 99% of the Belgian population (approximately 11 million people), the risk of undergoing a major lower extremity amputation in Belgium gradually declined for individuals between 2009 and 2013. Many reports have demonstrated that Figure 2. Major lower extremity amputation in adults with diabetes, 2013 (or nearest year). a substantial decrease in the incidence of major amputations, as well as a de- VAN DEN BERG from cover with its highly fatal course make this dis- to explain. For example, Germany has a crease in the total incidence of am- ease an underrecognized major threat to rate of amputation more than 18 times putations in people with diabetes, is public health.1 higher than Hungary (18.4 vs 1.1 per feasible after the implementation of 100,000). The result for Germany may multidisciplinary and trans-sectoral Major amputation is CLI SITUATION IN EUROPE be biased by a higher number of minor programs for diabetic foot ulcer care The Organization for Economic amputations in the numerator or lack of and prevention. A new finding of this associated with shorter Cooperation and Development (OECD) accurate data, given that there is no na- was the strong decline in the major studied lower-extremity amputation tional register to verify the precision of amputation rate in people with diabe- survival time, higher (LEA) rates in people with diabetes these estimates. The data from these 26 tes, but not in people without diabe- from 26 European countries from 2000 countries show lower amputation rates tes. The relative risk comparing people risk of subsequent to 2011. The study showed a decline in in health systems financed by public with and without diabetes decreased amputation rates of more than 50% from taxation. The average difference in favor but remained high. The decline in the major amputation, a mean of 13.2 (median, 9.4; range, 4.1– of tax-based versus insurance-based sys- amputation rate in those with diabetes 28.1) to 7.8 amputations per 100,000 in tems is equal to 4.5 per 100,000 diabetic was particularly prominent for major and higher healthcare the general population. Despite the de- amputations (Figure 1).11 amputations above the knee. A weaker, cline, still in 2011 an amputation attrib- In a similar study that examined a time but still significant decrease in the am- costs. uted to diabetes occurred every 7 min- period between 2000 and 2013, Carinci putation rate for minor lower extrem- utes (216 amputations per day). Variability et al reported a mean reduction of major ity amputations with and without dia- between countries exists and is difficult amputations in the general population betes was also observed.14

June 2020 CLIGLOBAL 15

Figure 3. Lower extremity amputation rates in diabetes according to different definitions, year 2013, or last year available, OECD data collection 2013.12 Used with permission from Springer Nature.

CLI SITUATION IN GERMANY performed in order to evaluate the op- amputations in the Netherlands over a pe- all lower-extremity amputations in Type A study by Heyer et al showed that tions for endovascular or surgical revas- riod of 10 years. The incidence decreased 1 diabetes of 87.5% for men and 47.4% the amputation rates per patient in cularization, the risk of major amputation by 26% in men and 38% in women with for women. It showed in incidence of all Germany have remained stable in the can be 90% lower.17 diabetes. A clear explanation for the dif- lower-extremity amputations in Type 2 overall population, while a slight decline ference in growth in the numbers of in- diabetes a decrease of 83% for men and in patients with both diabetes mellitus CLI SITUATION IN THE dividuals with diabetes between men and 79.1% for women (P<.001). No signifi- and with arterial occlusive disease be- NETHERLANDS women is lacking. The prevalence of dia- cant change in cadence of minor ampu- tween 2006 and 2012 was seen. The au- A study by van Houtum et al, including betes diagnoses in the U.S. also showed tations was noted. Due to improvements thors recommend the implementation data from 1991 to 2000 from the Dutch a greater increase in men than women.19 in metabolic risk factor and lifestyle factor of intensified preventive measures that National Medical Register, showed that The increase in the prevalence of dia- management, increased emphasis on early are considered crucial to the permanent in 1991, a total of 1,687 patients with betes in the Netherlands was marked and and aggressive treatment of foot ulcer and reduction in the number of amputa- diabetes had been admitted 1,865 times in agreement with previous reports that better patient education may have con- tions of the lower extremities.15 for 2,409 amputations. In 2000, a total of predicted an increase in the prevalence tributed to these results.21 In a retrospective analysis of the database 1,673 patients with diabetes were admit- of diabetes, resulting partly from demo- of the largest public health insurance in ted 1,932 times for 2,448 amputations. graphic changes.20 CLI SITUATION IN ITALY Germany, which included all in- and out- The overall incidence rates of the num- The authors concluded that the incidence A study conducted using the National patient diagnoses and procedural data ob- ber of patients who underwent lower of individuals with diabetes who are hospi- Hospital Discharge Record database for tained from a cohort of 418,882 patients extremity amputations decreased over talized for lower-extremity amputations is the period 2001 to 2010 looked at lower hospitalized due to PAD during 2009 to the years from 55.0 to 36.3 per 10,000 decreasing in the Netherlands, but despite extremity amputations in persons with and 2011, including a follow-up until 2013, it patients with diabetes (P<.05). This ris- this, there is still room for improvement. It without diabetes in Italy. The study showed was shown that 44% of amputees with CLI ing population with diabetes combined is possible that increased use of minor am- a reduction of major amputations during did not undergo a diagnostic angiogram with a decline in major amputations re- putations may result in a lower incidence the study period of patients with diabe- in the hospital prior to their amputation. flects an increased attention toward the of major amputations, with their impact on tes (30.7%) and without diabetes (12.5%). When taking into account a 24-month diabetic foot. The number of hospitals in patients’ quality of life. Therefore, more must The rates of minor amputations for those time frame prior to the amputation, the the Netherlands with access to podiatrists be done regarding selection of amputation without diabetes increased 22.4% and those number of patients without angiography increased from 32% in 1995 to 72% in level, possibly enabling a decrease in high- without diabetes remained stable. These or revascularization attempt during the in- 2000. The number of multidisciplinary level amputations.18 data reflect an improvement in the quality dex hospitalization, or the 2 years before, foot clinics increased from 16% to 40% in of diabetes therapy as well as in the overall was slightly lower, but still 37%.16 the same time frame.18 CLI SITUATION IN DENMARK approach to diabetic foot care such as the This information is particularly dis- The first striking observation in the A study by Jorgensen et al of a inclusion of peripheral vascular revascular- turbing as many studies, including one by study was the decrease in the num- Danish diabetic specialist center from izations, for example.22 Henry et al, report that if angiography is ber of diabetes-related lower extremity 2000 to 2011 showed an incidence of Continued on page 18

June 2020 16 CLIGLOBAL COVID-19 from cover communication with the east coast con- New Zealand government went hard and regions in different severity stages and firms that CLI patients are being seen in went early on a complete isolation and therefore all recommendations cannot be test immediately upon admission to the the clinic setting as much as possible and lockdown that I believe helped us. One of generalized. In areas with high infection emergency room and likely wait to treat being kept out of the ER. Minor pro- the things we did right from the beginning rate, testing is important. However, you until results were known. In the interim, cedures needing to be done urgently are was to state that any CLI patient present- may have 4–6 hours to wait for the test. the patient would be started on anticoag- being done in the outpatient setting as ing acutely would be treated acutely in our In areas with low infection rates, I believe ulation and antiplatelet therapy. “We have much as possible. hospital system with the kind of protection we can proceed with our standard tech- seen an anecdotal change in the last several mentioned earlier. As we open up more of nique and procedural steps to take care of weeks to a less liberal stance to intubate Q: There has been a lot of talk of our clinics, we have been swamped with patients and staff. COVID-19 patients due to the dismal arterial and venous thrombosis in late-presenting CLI patients who have been prognosis for those who are intubated. We the COVID environment. battling on at home despite huge advertis- Dr. Mustapha: This pandemic forced have adopted an almost never intubate ap- What is your opinion of the risk of ing campaigns urging patients not to wait us to become more efficient and nim- proach to these patients. I think this ap- COVID to patients with CLI and vice versa? to seek needed therapy.” bler to address the urgent needs of CLI proach is being replicated around the New A: Dr. Lookstein reports anecdotally see- patients while adapting to the changing York area. Intubation is not considered ing a massive uptick in large vessel strokes Q: As we are starting to look at re- environment. benign and is really viewed as a high-risk in a unique population much younger than covery in various parts of the world, intervention, even for emergent cases.” typically seen. We are seeing patients who will we see a deliberate attempt to Dr. van den Berg: I think what we Dr. Richard Neville, from Virginia, underwent endovascular therapy in the push things more into the ambula- have learned from this pandemic is that in stated that just a couple of weeks ago last 6 months coming in with a complete tory space than they were before? addition to all the damage that was done his institution may not have even inter- thrombosis of the infrainguinal circulation, A: Dr. Mustapha stated, “Actually, I by the virus, there is a lot of collateral vened on this patient who would have where the typical presentation would be a see the future to be right for CLI centers damage due to delayed treatment affect- been considered a Tier 2 patient. These focal restenosis. This is mostly not a chronic like ours because the patients can be iso- ing patients with CLI, but also patients patients would instead get treatment after CLI population, however, but rather a more lated, you can control who comes in and who need to postpone oncology treat- 48 hours. However, over the past couple ALI population. out, you can deliver the majority of care ment among other things. We are bracing of weeks, the window has been expanded, you need to delivery, and the safety is ex- for the impact when we can fully reopen and now Tier 2, or urgent, cases are be- Q: Who in hospital administration tremely good. I look forward to a future our activity. We need to be prepared for ing intervened upon immediately. If the in the United States came up with with more CLI centers. For me, it’s been longer working days. patient has any symptoms, they would be the theory that procedures like CLI a great experience.” tested. Without symptoms, standard pre- are not important and urgent pro- Dr. Driver: The bottom line is that cautions would be followed. cedures to be done? What is the Q: Germany has had the lowest we are still fighting for our patients. In the CLI Global Society’s statement on mortality rate of almost any place middle of a pandemic, if not treated, these Q AND A this matter? in the world. Does this translate patients are going to lose their limb or their A: Dr. Katzen responded on behalf of into a population less fearful of life. We have to keep fighting for them and Q: What are your thoughts on test- the Board with assurance that they believe hospitals? help them understand the best way to get ing for everybody? CLI is an urgent, life threatening disease A: Dr. Zeller stated, “This differs from care from us. We can’t back down. A: Dr. Michael Jaff responded, “From a that needs to be addressed in that manner. region to region in Germany. In my area staff standpoint, it is reassuring and shows The goal is to prevent loss of life and loss we have an infection rate of less than 2% Dr. Holden: Planning and prepara- empathy and concern. Anything we can of limb. The CLI Global Society supports at the moment. In our institution and our tion is important. There is a large, silent do to reassure staff is of great value. We this type of therapy as needing urgent and area, patients do not seem to fear coming group of patients who are going to turn need to keep in mind the facts regarding emergent attention. Dr. Neville’s experi- to the hospital. So, we did not have the up in the next few weeks. I believe there acute diagnosis: active viral shedding tests ence is not necessarily that the administra- experience of patients coming in with is always a positive and there are oppor- were designed to diagnose sick patients tion thinks CLI is any less important, but delayed treatment. We did inform our tunities that will come from this, oppor- and not designed to screen populations of rather they were dealing with a utilization physicians right from the beginning to tunities to be more efficient and improve asymptomatic patients. The false negative problem. “We saw what was happening refer CLI patients for therapy. We are not the way we communicate with patients rates, in my view, are unacceptable and in New York and it scared the heck out experiencing an increase in amputation; I and educate our colleagues. Take this we- give people a false sense of security.” Dr. of everybody. The response was to shut believe due to this. binar for example. We should embrace Jaff underscored the fact that staff should down at first to reserve resources. We’ve the good things that come out of it. know you care and are trying to protect now backed off on that after having se- Q: What is happening in wound them as best you can. cured resources. However, I do think we centers? How far can telehealth go Dr. Neville: I think the importance potentially are going to see an increase in for this population? of the CLI Global Society is now more Q: Are patients comfortable being amputations during this COVID period A: Dr. Driver responded, “These are important than ever in terms of raising treated in an outpatient setting ver- due to this.” Dr. Jaff, as a former hospital very important questions because patients awareness and advocating for our patients. sus a hospital and what type of pro- administrator, stated that the hospital ad- are being left behind. Programs with good tection are you providing? ministrators were not the decision makers. telehealth are critically important. If you Dr. Lookstein: I am very proud to A: Dr. Jihad Mustapha, who performs “The truth of the matter is that Medicare, have a patient with a CLI diabetic foot say that at our institution none of the staff CLI revascularization in a busy outpatient American College of Surgeons, and with potential sepsis, it is critical to get have become symptomatic despite hav- CLI center in Michigan, described see- American College of Cardiology came them in front of a provider. Many wound ing done hundreds of cases over the past ing an increase in patients being referred out with guidelines. Quite frankly, our care centers are completely closed down. weeks, with close to 150 of those being from the hospital systems to the outpa- voice wasn’t loud enough.” Centers of excellence, particularly with COVID positive. I think that is because tient center for treatment. “Hospitals are combined vascular and podiatric special- we’ve all come together as a dedicated performing fewer non-COVID proce- Q: Do you feel that treating CLI in ists, that are separate from the hospital are team motivated to do the right thing. dures and patients fear going to a hospital the COVID era conveys a higher being allowed to stay open. But there are This is a testament to how you can be setting. We provide screening of patients risk for the CLI patient? not many of them.” Dr. Neville reports successful and understand you can over- and staff and provide adequate PPE for A: Dr. Mustapha responded, “CLI pa- that his organization has four wound cen- come the challenges we are all facing. our staff. Patients are comforted by be- tients are fragile. Treating them now in ters. Their volume is down about 50%. “As ing treated in an environment where they this era to keep them out of the hospital we protocolize who is to be seen at our Dr. Jaff: I am heartened by how the believe their risk of exposure is less.” is more important than ever before.” wound centers, we are hoping to stretch scientific community around the world telemedicine to 80% of all visits. We are has banded together to share data. As we Q: What are you seeing in the Q: Is COVID less disruptive in New currently at about 60%.” come out of this, the voice of the physi- United States regarding urgent ver- Zealand? cian is going to be even more important. sus emergent treatment for patients A: Dr. Holden responded, “One of LESSONS LEARNED This is particularly new to us because the with CLI needing podiatric surgery? the advantages of living on a couple of Professor Zeller: I believe what US is going to have to figure out how to A: Dr. Driver reports that her expe- islands in the South Pacific may have af- we’ve learned during this discussion is rebuild healthcare again and we need to rience now on the west coast and her forded some protection. However, the that the pandemic is hitting different have a loud and upfront voice. n

June 2020 CLIGLOBAL 17

Figure 1. 85-year-old male with Figure 2. Orbital atherectomy with a Figure 3. Balloon angioplasty with a Rutherford class 3 claudication with Figure 4. Final angiographic result. severely calcified CFA disease. 1.5-mm crown. 6- x 40-mm drug-coated balloon.

LEE from page 3 extremity. PVI of the DFA is uncom- 5. Bonvini RF, Rastan A, Sixt S, et al. Endovascular treat- 7. Siracuse JJ, Van Orden K, Kalish JA, et al; Vascular Quality monly performed because angiographic ment of common femoral artery disease: medium- Initiative. Endovascular treatment of the common femo- term outcomes of 360 consecutive procedures. J Am ral artery in the Vascular Quality Initiative. J Vasc Surg. at the inguinal ligament, as it may lead to complications may lead to critical limb Coll Cardiol 2011;58:792–798. 2017 Apr;65(4):1039-1046. Epub 2016 Dec 29. stent fracture. An interwoven nitinol stent ischemia if it is the last remaining conduit 6. Lee MS, Heikali D, Mustapha J, et al. Acute pro- 8. Lee MS, Srivastava PK, Al Yaseen S, et al. Acute proce- like the Supera stent (Abbott) is flexible to the lower limb. In 282 patients who un- cedural outcomes of orbital atherectomy for the dural outcomes of orbital atherectomy for the treat- treatment of common femoral artery disease: Sub- ment of profunda femoris artery disease: Subanalysis and may lower the risk of stent fracture derwent isolated DFA disease, the techni- analysis of the CONFIRM Registries. Vasc Med. of the CONFIRM Registries. J Invasive Cardiol. compared to other nitinol stents. However, cal success rate was 94%, and the 30-day 2017;22(4):301-306. 2018;30:177-181. the Supera stent strut design is not very mortality rate was 1.8%.7 We reported that conducive to ballooning the side branch. orbital atherectomy of the DFA was asso- This may pose a challenge in the setting of ciated with a low rate of the composite distal bifurcation involvement of the CFA, of flow-limiting dissection, perforation, which could lead to compromise of the slow flow, vessel closure, spasm, embolism, deep femoral artery (DFA). Bifurcation le- or thrombosis.8 However, the number of sions are also associated with increased risk patients in our study was low and limited of procedural failure and a trend toward to short-term follow-up. higher 1-year rates of restenosis and tar- In summary, controversy surrounds the get lesion revascularization.5 The presence ideal revascularization strategy for CFA Call for Manuscripts / Peripheral Vascular Disease of a stent in the CFA could make arte- disease. Surgery has long been considered rial access and the use of a vascular closure the gold standard. However, despite the Vascular Disease Management (VDM), considers manuscripts on all topics relevant device to achieve hemostasis more diffi- technical success of surgery, it is associ- to diagnosing and treating peripheral vascular disease. cult. Stenting of the CFA may hinder the ated with complication rates. PVI of the option of CFE. The rates of restenosis and CFA is associated with less procedural Multi-disciplinary: The VDM audience includes vascular surgeons, podiatrists, target lesion revascularization are higher mortality and morbidity compared with neurosurgeons, nephrologists, interventional radiologists, and cardiologists. after PVI of calcified lesions. surgery. PVI may represent a paradigm www.vasculardiseasemanagement.com Strategies to improve procedural suc- shift for the treatment of CFA disease. n cess rates in heavily calcified CFA include Composition: • Clinical Reviews • Practice Management • Clinical Images • New Technologies the use of athereoablative devices and Disclosure: None. • Original Research • Endovascular Techniques • Case Studies • Editorials • Brief Reports intravascular lithotripsy (Figures 1–4). We reported that orbital atherectomy Dr. Lee can be reached by email at MSLee@ Aims/Purpose/Importance: Vascular Disease Management (VDM) is a peer- appeared to be safe and effective for the mednet.ucla.edu reviewed journal focusing on the treatment of peripheral vascular disease, a treatment of severely calcified CFA.6 The fast-growing field in both importance and patient volume. As diagnosis and primary endpoint of angiographic com- REFERENCES treatment options develop rapidly, VDM aims to keep the clinician abreast of plication, defined as the composite of 1. Ballotta E, Gruppo M, Mazzalai F, et al. Common these complex technical and treatment advances. A single issue of VDM may femoral artery endarterectomy for occlusive disease: discuss topics in numerous subject areas all relevant to vascular disease: lower dissection, perforation, slow flow, closure, an 8-year single-center prospective study. Surgery. spasm, embolism, or thrombosis at 30 2010;147:268-274. limb salvage, carotid stenting, embolic protection, abdominal aortic aneurysm, days, was lower in the CFA group com- 2. Nguyen BN, Amdur RL, Abugideiri M, et al. magnetic resonance imaging techniques, and management of diabetic patients. Postoperative complications after common femoral pared with the SFA group (17% vs. 24%, endarterectomy. J Vasc Surg. 2015;61:1489–1494.e1. Address submission questions to P=.02), driven by a lower dissection rate 3. GouëfficY, Della Schiava N, Thaveau F, et al. Stenting (10% vs. 15%, P=.04). or surgery for de novo common femoral artery steno- Sonia Guimil, PhD, Managing Editor, Email: [email protected] sis. JACC Cardiovasc Interv. 2017;10:1344-1354. One of the disadvantages of PVI of the 4. Davaine JM, Quillard T, Chatelais M, et al. Bone like Please submit your manuscript using our web-based submission portal: CFA is that it may compromise the DFA, arterial calcification in femoral atherosclerotic lesions: which may be the last vascular conduit prevalence and role of osteoprotegerin and pericytes. www.editorialmanager.com/vdm/default.aspx Eur J Vasc Endovasc Surg. 2016;51:259–267. providing collateral flow to the lower

June 2020 18 CLIGLOBAL VAN DEN BERG from page 15 amputation. Ethnicity and social deprivation play a significant role, but it CLI SITUATION IN SPAIN is the role of diabetes and its complica- It is possible that increased use of minor López-de-Andrés et al studied Spanish tions that is most profound. Significant national data from 2001 to 2008 that in- reduction in the incidence of low- amputations may result in a lower incidence cluded 46,536 minor lower extremity er extremity amputation have been amputations (LEAs) and 43,528 major shown in specific at-risk populations of major amputations, with their impact on LEAs. In patients with Type 1 diabetes, after the introduction of specialist dia- the incidence of minor and major am- betic foot clinics. patients’ quality of life. putations decreased significantly from Patients initially diagnosed with CLI 2001 to 2008 (0.88–0.43 per 100,000 in- suffer poor long-term prognosis and gen- habitants and 0.59–0.22 per 100,000 in- erate high healthcare costs. Long-term habitants, respectively). In patients with survival and cost are comparable between 1993;2(1):11–14. outcomes and lack of guideline adherence. Eur Heart Type 2 diabetes, the incidence of minor revascularization techniques (surgical and 7. Bekwelem W, Bengtson LG, Oldenburg NC, et al. J. 2015;36(15), 932-938. https://doi.org/10.1093/ and major LEAs increased significantly endovascular). Compared with each ap- Development of administrative data algorithms to eurheartj/ehv006 identify patients with critical limb ischemia. Vasc Med. 17. Henry AJ, Hevelone ND, Belkin M, Nguyen LL. (9.23–10.9 per 100,000 inhabitants and proach, primary major amputation is as- 2014:19:483-490. Socioeconomic and hospital-related predictors of 7.12–7.47 per 100,000 inhabitants). The sociated with shorter survival time, high- 8. Conte MS, Bradbury AW, Kolh P, et al. Global vascular amputation for critical limb ischemia. J Vasc Surg. decrease in LEAs in Type 1 diabetes may er risk of subsequent major amputation, guidelines on the management of chronic limb-threat- 2011;53(2):330-339.e1. https://doi.org/10.1016/j. ening ischemia. J Vasc Surg. 2019;69(6S), 3S-125S.e40. jvs.2010.08.077 be related to more strictly controlled risk and higher healthcare costs. It is clear that https://doi.org/10.1016/j.jvs.2019.02.016 18. van Houtum WH, Rauwerda JA, Ruwaard D, Schaper factors in these patients. The increased considerable efforts are needed to raise 9. Mustapha JA, Katzen BT, Neville RF, et al. Disease NC, Bakker K. Reduction in diabetes-related lower- burden of amputations in patients with disease awareness, implement coding to burden and clinical outcomes Following initial diag- extremity amputations in The Netherlands: 1991- nosis of critical limb ischemia in the medicare popula- 2000. Diabetes Care. 2004;27(5):1042-1046. https:// Type 2 diabetes suggests that diabetic foot better define and identify the disease, tion. JACC Cardiovasc Interv. 2018;11(10):1011-1012. doi.org/10.2337/diacare.27.5.1042 care in Spain remains suboptimal.23 refine diagnostic algorithms, establish https://doi.org/10.1016/j.jcin.2017.12.012. 19. Centers for Disease Control and Prevention (CDC): A similar study in Spain by Rubio et evidence-based treatment pathways, and 10. American Cancer Society. Cancer statistics center Prevalence of diabetes and impaired fasting glu- https://cancerstatisticscenter.cancer.org/?_ga= cose in adults: United States, 1999-2000. MMWR al compared amputation rates in people address the high mortality rates associated 2.39975970.1231753458.1537645337- 2003;52:833-837. with and without diabetes during two with this diagnosis.26 1450708034.1537467257#!/. 20. Ruwaard D, Hoogenveen RT, Verkleij H, Kromhout periods: before (2001–2007) and after Please join the CLI Global Society at Accessed September 21, 2018. D, Casparie AF, van der Veen EA. Forecasting the num- 11. Carinci F, Massi Benedetti M, Klazinga NS, Uccioli ber of diabetic patients in the Netherlands in 2005. (2008–2011) the introduction of the cliglobalsociety.org to contribute to global L. Lower extremity amputation rates in people with Am J Public Health 1993;83:989-995. Multidisciplinary Diabetic Foot Unit. A efforts to eliminate unnecessary amputa- diabetes as an indicator of health systems performance. 21. Jørgensen ME, Almdal TP, Faerch K. Reduced incidence significant reduction in major amputations due to critical limb ischemia. n A critical appraisal of the data collection 2000-2011 of lower-extremity amputations in a Danish diabetes pop- by the Organization for Economic Cooperation ulation from 2000 to 2011. Diabet Med. 2014;31(4):443- tions in people with diabetes was shown, and Development (OECD). Acta Diabetologica, 447. https://doi.org/10.1111/dme.12320 from 6.1 per 100,000 per year (2001– Disclosures: None. 2016;53(5):825-832. https://doi.org/10.1007/ 22. Lombardo FL, Maggini M, De Bellis A, Seghieri G, 2007) to 4.0 per 100,000 per year (2008– s00592-016-0879-4 Anichini R. Lower extremity amputations in persons 12. Carinci F, Uccioli L, Massi Benedetti M, Klazinga with and without diabetes in Italy: 2001-2010. PLoS 24 2011) (P=.020). REFERENCES NS. An in-depth assessment of diabetes-related lower One. 2014;Jan 28;9(1):e86405. doi: 10.1371/journal. 1. Mustapha JA, Katzen BT, Neville RF, et al. Critical limb extremity amputation rates 2000-2013 delivered by pone.0086405. eCollection 2014. ischemia: a threat to life and limb. Endovascular Today. twenty-one countries for the data collection 2015 23. López-de-Andrés A, Martínez-Huedo MA, Carrasco- CLI SITUATION IN THE 2019: 18(5). https://evtoday.com/articles/2019-may/ of the Organization for Economic Cooperation Garrido P, et al. Trends in lower-extremity amputa- UNITED KINGDOM critical-limb-ischemia-a-threat-to-life-and-limb. and Development (OECD). Acta Diabetologica. tions in people with and without diabetes in Spain, A study published in Diabetes Medicine 2. Norgren L, Hiatt WR, Dormandy JA, et al. 2020;57(3):347-3579. https://doi.org/10.1007/ 2001-2008. Diabetes Care. 2011;34(7):1570-1576. Inter-Society Consensus for the Management of by Moxey et al showed that the variation s00592-019-01423-5 https://doi.org/10.2337/dc11-0077 Peripheral Arterial Disease. Eur J Vasc Endovasc Surg. 13. OECD. Diabetes care. 2015;134–135. https://doi. 24. Rubio JA, Aragón-Sánchez J, Jiménez S, et al. in incidence of amputation across the 2007;33:S1-S70. org/10.1787/health_glance-2015-45-en Reducing major lower extremity amputations after United Kingdom ranges in rates from 3.9 3. CLI Volume I, USA 2016ent, Sage Group. 14. Claessen H, Avalosse H, Guillaume J, et al. the introduction of a multidisciplinary team for the di- 4. Goodney PP, Travis LL, Nallamothu BK, et al. Variation to 7.2 per 100,000 (P <.0001).25 These Decreasing rates of major lower-extremity amputa- abetic foot. Int J Low Extrem Wounds. 2014;13(1):22- in the use of lower extremity vascular procedures for tion in people with diabetes but not in those with- 26. https://doi.org/10.1177/1534734614521234 differences are mainly related to the vari- critical limb ischemia. Circulation. Cardiovascular out: A nationwide study in Belgium. Diabetologia, 25. Moxey PW, Gogalniceanu P, Hinchliffe RJ, et al. Lower ability in implementation of specialized Quality and Outcomes. 2012;5(1):94–102. https://doi. 2018;61(9):1966–1977. https://doi.org/10.1007/ extremity amputations—A review of global variability org/10.1161/CIRCOUTCOMES.111.962233 diabetic foot care. s00125-018-4655-6 in incidence. Diabet Med. 2011;28(10):1144-1153. 5. Nehler MR, Duval S, Diao L, et al. Epidemiology 15. Heyer K, Debus ES, Mayerhoff L, Augustin M. https://doi.org/10.1111/j.1464-5491.2011.03279.x of peripheral arterial disease and critical limb isch- Prevalence and regional distribution of lower limb am- 26. Mustapha JA, Katzen BT, Neville RF, et al. CONCLUSION: CLI IS A emia in an insured national population. J Vasc Surg. putations from 2006 to 2012 in Germany: A population- Determinants of long-term outcomes and costs in 2014;60(3), 686-695.e2. https://doi.org/10.1016/j. based study. Eur J Vasc Endovasc Surg. 2015;50(6):761- the management of critical limb ischemia: A popula- GLOBAL SITUATION jvs.2014.03.290. 766. https://doi.org/10.1016/j.ejvs.2015.07.033 tion-based cohort study. J Am Heart Assoc. 2018;Aug Significant global variation exists 6. Catalano M. (1993). Epidemiology of criti- 16. Reinecke H, Unrath M, Freisinger E, et al. Peripheral 21;7(16), e009724. https://doi.org/10.1161/ in the incidence of lower extremity cal limb ischaemia: North Italian data. Eur J Med. arterial disease and critical limb ischaemia: Still poor JAHA.118.009724

GERAGHTY from page 4 amputation-free and overall survival in patients randomized to a bypass surgery-first or a balloon an- DEEP Clinical drug-coated balloon trial: 5-year out- 12. Scheinert D, Katsanos K, Zeller T, et al. A prospective gioplasty-first revascularization strategy. J Vasc Surg. comes. JACC Cardiovasc Interv. 2020;13(4):431-443. randomized multicenter comparison of balloon an- Correspondence: Patrick J. Geraghty, MD, 2010;51(5 Suppl):5s-17s. 9. Zeller T, Baumgartner I, Scheinert D, et al. Drug- gioplasty and infrapopliteal stenting with the sirolim- 4. Bradbury AW, Adam DJ, Bell J, et al. Bypass ver- eluting balloon versus standard balloon angioplasty us-eluting stent in patients with ischemic peripheral Section of Vascular Surgery, Washington sus Angioplasty in Severe Ischaemia of the Leg for infrapopliteal arterial revascularization in critical arterial disease: 1-year results from the ACHILLES University School of Medicine, 660 S. Euclid (BASIL) trial: A survival prediction model to facili- limb ischemia: 12-month results from the IN.PACT trial. J Am Coll Cardiol. 2012;60(22):2290-2295. Avenue, Campus Box 8109, St. Louis, MO tate clinical decision making. J Vasc Surg. 2010;51(5 DEEP randomized trial. J Am Coll Cardiol. 13. Spreen MI, Martens JM, Knippenberg B, et al. Long- 63110. Email: [email protected] Suppl):52s-68s. 2014;64(15):1568-1576. term follow-up of the PADI Trial: percutaneous 5. Popplewell MA, Davies H, Jarrett H, et al. Bypass 10. Zeller T, Beschorner U, Pilger E, et al. Paclitaxel- transluminal angioplasty versus drug-eluting stents REFERENCES versus angioplasty in severe ischaemia of the leg - coated balloon in infrapopliteal arteries: 12-month for infra-popliteal lesions in critical limb ischemia. J 2 (BASIL-2) trial: study protocol for a randomised results from the BIOLUX P-II Randomized Trial Am Heart Assoc. 2017;6(4). 1. Shishehbor MH, White CJ, Gray BH, et al. Critical controlled trial. Trials. 2016;17:11. (BIOTRONIK’S-first in man study of the Passeo-18 14. Rastan A, Brechtel K, Krankenberg H, et al. Limb Ischemia: An Expert Statement. J Am Coll 6. Menard MT, Farber A. The BEST-CLI trial: a mul- LUX drug releasing PTA balloon catheter vs. the un- Sirolimus-eluting stents for treatment of infrapopli- Cardiol. 2016;68(18):2002-2015. tidisciplinary effort to assess whether surgical or en- coated Passeo-18 PTA balloon catheter in subjects teal arteries reduce clinical event rate compared to 2. Conte MS, Bradbury AW, Kolh P, et al. Global vascu- dovascular therapy is better for patients with critical requiring revascularization of infrapopliteal arteries). bare-metal stents: long-term results from a random- lar guidelines on the management of chronic limb- limb ischemia. Semin Vasc Surg. 2014;27(1):82-84. JACC Cardiovasc Interv. 2015;8(12):1614-1622. ized trial. J Am Coll Cardiol. 2012;60(7):587-591. threatening ischemia. J Vasc Surg. 2019;69(6s):3S- 7. Menard MT, Farber A, Assmann SF, et al. Design and 11. Mustapha JA, Brodmann M, Geraghty PJ, Saab F, 15. Bosiers M, Scheinert D, Peeters P, et al. Randomized 125S.e140. rationale of the best endovascular versus best surgi- Settlage RA, Jaff MR. Drug-coated vs uncoated per- comparison of everolimus-eluting versus bare-metal 3. Bradbury AW, Adam DJ, Bell J, et al. Bypass ver- cal therapy for patients with critical limb ischemia cutaneous transluminal angioplasty in infrapopliteal stents in patients with critical limb ischemia and in- sus Angioplasty in Severe Ischaemia of the Leg (BEST-CLI) trial. J Am Heart Assoc. 2016;5(7). arteries: six-month results of the Lutonix BTK Trial. frapopliteal arterial occlusive disease. J Vasc Surg. (BASIL) trial: An intention-to-treat analysis of 8. Zeller T, Micari A, Scheinert D, et al. The IN.PACT J Invasive Cardiol. 2019;31(8):205-211. 2012;55(2):390-398.

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