supplement to Cath Lab Digest

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1 HIGHLIGHTS From the 8th Annual AMPutation Prevention Symposium AUGUST 8 11, 2018 supplement to Cath Lab Digest Supplement to Cath Lab Digest November

2 Table of Contents 4 Step by Step: How and Why to Obtain Hybrid Access for the Complex CLI Patient Jeffrey Wang, MD; Dustin Yoon, MD BARD Ad Intended for IC, VS and IR fellows, BD Bard Advance has developed an exceptional Fellow Series focused on expanding your endovascular skill set. Utilizing a multi-disciplinary, multi-modal educational platform, you will learn from leading experts current data and the latest technological advances in the treatment of peripheral vascular disease. We invite you to join us. Please contact your local BD Bard representative or us at BPV.Advance@bd.com JOIN ADVANCE FELLOWS SERIES ADVANCE A CLINICAL TRAINING & EDUCATION PROGRAM FELLOWS SERIES Access Where You Need to When You Must Save a Limb: Learn the Latest Tactics George Adams, MD, MHS, MBA, FACC, FSCAI Lutonix DCB Global BTK Registry Study 12-Month Interim Outcomes Marianne Brodmann, MD Build a CLI Program in 1 Year: It s Not Impossible Paul Michael, MD, FSCAI Plaque Morphology from A to Z and PRIME Registry CTOP Analysis Fadi Saab, MD, FAGG, FSCAI, FASE Claim Analysis Summary on CLI Mortality and Morbidity Jihad Mustapha, MD 24 Are All CLI Cases Created Equal? Tom Davis, MD, FACC 28 Data-Driven vs Policy-Driven Decisions for DCB Therapy Craig Walker, MD Critical limb ischemia (CLI) is one of the fastest growing diseases. My fear is that one day it will reach epidemic proportions for those patients predisposed to the disease. Hence, my reason for developing the AMPutation Prevention Symposium (AMP), which is the only medical meeting focused exclusively on CLI. Every year, we work hard as a team to bring together knowledge, experience, and data from around the globe. We share with our audience what has happened over the last 12 months that could help slow down the growth of CLI, along with all its associated morbidities and mortality. At AMP this year, we learned of significant new devices specifically made for CLI. This is a great victory for our patients, because now we are gaining tools to treat the complex, difficult CLI disease state. As AMP continues to evolve, we have seen an avalanche of data that support the outcome of what we do on a daily basis. I, for one, don t expect a one-treatment-fits-all approach, now or ever. This year at AMP, I listened to faculty describing how each and every CLI patient was treated by different approaches, and despite different approaches, each patient did well. That tells me one thing and one thing only the common denominator to improve outcomes for our CLI patients is simply to treat them! AMP strives to continue fueling the discussion and call for additional data so that one day we will reach a consensus on a therapeutic approach for CLI patients BD. BD, and the BD Logo are trademarks of Becton, Dickinson and Company. All Rights Reserved. Bard Peripheral Vascular, Inc W. 3rd Street Tempe, AZ BPV/PEGE/0818/ HMP. All rights reserved. Reproduction in whole or in part prohibited. Opinions expressed by authors, contributors, and advertisers are their own and not necessarily those of HMP, the editorial staff, or any member of the editorial advisory board. HMP is not responsible for accuracy of dosages given in articles printed herein. The appearance of advertisements in this journal is not a warranty, endorsement or approval of the products or services advertised or of their effectiveness, quality or safety. Rapid advances in medicine may cause information contained here to become outdated, invalid or subject to debate. Accuracy cannot be guaranteed. HMP disclaims responsibility for any injury to persons or property resulting from any ideas or products referred to in the articles or advertisements. Content may not be reproduced in any form without written permission. Rights, Permission, Reprint, and Translation information is available at HMP is the force behind Healthcare Made Practical and is a multichannel leader in healthcare events and education, with a mission to improve patient care. The company produces accredited medical education events and clinically relevant, evidence-based content for the global healthcare community across a range of therapeutic areas. For more information, visit hmpglobal.com.

3 Step by Step: How and Why to Obtain Hybrid Access for the Complex CLI Patient Jeffrey Wang, MD 1,* ; Dustin Yoon, MD 1 Horizon Vascular Specialists; Rockville, Maryland 1 Disclosures: Consultant Boston Scientific, Cardiovascular Systems, Inc.* Speakers Bureau Janssen* Introduction Hybrid access is defined as a combination of open surgery and endovascular procedures. It s obtained by opening or placing a conduit, which is subsequently accessed for use in an endovascular procedure. Hybrid access can be concomitant (the bypass is performed and then the operator goes down the bypass and intervenes distally during the same session), or it can be staged. Typically, the endovascular procedure is performed distal to the open procedure. Common Open Procedures Used in Hybrid Access Common femoral artery (CFA) endarterectomy with subsequent distal intervention is (or should be) the most frequently performed hybrid access procedure. Other common hybrid procedures include femoral popliteal bypass and femoral distal bypass. Hybrid procedures such as mesenteric bypass with stenting are also common but are not pertinent to the critical limb ischemia patients under discussion herein. Common Reasons for Hybrid Access Several factors might indicate the need for hybrid access. The first, and most common reason, is the inability to cross the proximal lesion; this might occur for a multitude of reasons. A second reason is an unfavorable disease location, wherein a vessel (such as the CFA) is not suitable for an endovascular procedure. A third situation for hybrid access occurs when an artery is damaged or ligated during a Figure 1. The occlusion is visible in the common femoral artery. Figure 2. The removal of the occlusion during endarterectomy. previous procedure; such damage might not necessarily be caused by an arterial intervention it might be orthopedic in nature or caused by any other trauma. A fourth reason for hybrid access is the presence of an occluded stent across a joint. For example, although it is possible to reopen a stent that is crossing a knee joint, the stent most likely won t stay open, especially in a patient who is particularly mobile. A fifth reason for a hybrid approach is the presence of foreign bodies in the artery. This can range from a traumatic perforation that occurs and causes embolization to a surgical procedure that violates the artery. Figure 3. Calcified plaque post-removal from the common femoral artery. The origins of the pro-funda and superficial femoral artery are visible. Case Example: Common Femoral Endarterectomy Hybrid A 62-year-old male presented with significant smoking history, diabetes, hypertension, and ischemic foot ulcerations. The patient had an occluded CFA as well as superficial femoral artery (SFA) disease. This case was staged, with endarterectomy of the CFA performed first, followed by SFA intervention. Stage 1. Although it would have been possible to cross the CFA lesion and perform angioplasty, the durability of such a procedure would be questionable due to the complete occlusion in this patient. Figures 1 and 2 illustrate the vessel before and after plaque removal, respectively, while the removed calcified plaque is shown in Figure 3. The patch across the top of the vessel is shown in Figure 4. The patient had runoff through his profunda, so at this point, the procedure was stopped, with future planned reintervention with endovascular procedures through the contralateral groin. This is primarily because the disease began near the orifice of the SFA, and it would therefore be advantageous to have some working distance before the first lesion was encountered. Stage 2. Post-endarterectomy angiogram showed the CFA endarterectomy portion of the vessel and a stenosis of the SFA in the area just past the intervened area (Figure 5). Angiography also showed mid-sfa disease and a distal SFA occlusion going into the popliteal artery. Due to the heavy degree of calcification that was evident after removing the plaque from the CFA and visible on Figure 4. A patch across the top of the vessel post-endarterectomy. Figure 5. An angiogram post-endarterectomy showing the common femoral endarterectomy portion of the vessel, as well as a stenosis of the superficial femoral artery. angiography, orbital atherectomy with subsequent angioplasty was performed, resulting in a reasonable level of revascularization in the leg (Figure 6). Femoral Posterior Tibial Bypass Hybrid This hybrid procedure was a concomitant intervention on a 61-year-old male patient who suffered an orthopedic misadventure that injured his knee in the distant past. The patient had an ischemic-looking foot that was progressively worsening, and a significant smoking history. Angiography was performed during an initial attempted endovascular intervention, but we were unable to get past an occlusion in the popliteal artery at the knee. There were several Figure 6. An angiography post-superficial femoral artery intervention with orbital atherectomy and angioplasty shows an acceptable level of revascularization in the leg. clips in the knee area that prevented the needle from entering the popliteal artery. We suspected the artery had been ligated with clips during the bleeding event of his previous orthopedic surgery. The patient was therefore taken for femoral to proximal posterior tibial artery bypass. The bypass is shown in Figure 7, which shows the white vessel loop around the artery and the bypass apparent just above the white loop. The patient had a good pulse at the site and a good signal at the posterior tibial above the ankle; however, I couldn t feel a pulse or get a signal just distal to the ankle. Therefore, I decided to cannulate the bypass with a butterfly needle (Figure 8). After the initial angiogram, I subsequently placed a 4 Supplement to Cath Lab Digest November 2018 Supplement to Cath Lab Digest November

4 Access Where You Need to When You Must Save a Limb: Learn the Latest Tactics George Adams, MD, MHS, MBA, FACC, FSCAI UNC Rex Healthcare, Garner, North Carolina Figure 7. Femoral to proximal posterior tibial artery bypass. The white vessel loop is around the artery, and the bypass is apparent just above the white loop. Figure 9. An occlusion (red arrow) is evident at the very distal aspect of the posterior tibial artery going into the plantars. sheath so I could intervene on whatever was found; the angiogram showed good flow in the patient s native posterior tibial and an occlusion at the very distal aspect of the posterior tibial artery going into the plantars (Figure 9). At this point, I placed a wire through the lesion, used orbital atherectomy on a calcified segment, and post-dilated with a 3 mm angioplasty balloon (Figures 10A- C). The patient subsequently had good flow through the lesion and perfusion through his foot (Figure 10D). Conclusion Hybrid access should not be the first option; it should be reserved for situations in which endovascular means cannot be pursued. However, if a CFA occlusion is present, CFA endarterectomy followed by the procedure of Figure 8. The bypass was cannulated with a butterfly needle. choice is advisable because it is difficult to obtain durable long-term results in that area using endovascular methods alone. In addition, potential complications in the CFA may jail out the profunda or prevent further interventions on the contralateral side, especially if stenting is done across that area. These procedures can be concomitant or staged. Therefore, if the surgical procedure doesn t lend itself to a good working area for the endovascular procedure (for example, if the operator prefers to work in the cath lab instead of the operating room), the endovascular procedure can potentially be moved out of the operating room and finished in the cath lab at a later date. The hybrid approach can be extremely useful in certain situations. A B C D Figure 10. A wire was placed through the lesion (A), orbital atherectomy was performed on a calcified segment (B), and the lesion was post-dilated with a 3-mm angioplasty balloon (C). The post-intervention result showed flow throughout the lesion and perfusion throughout the foot (D). Disclosures: Consultant Abbott Vascular, Asahi Intecc, Bard, Boston Scientific, Cook Medical, Cordis/Cardinal, CloSys, Cardiovascular Systems, Inc., Daicchi Sankyo, Gore, Intact Vascular, Lake Region Medical, Medtronic, Mercator MedSystems, Penumbra, Philips/Volcano, Roxwood Medical, Shockwave Medical, Spectranetics, Terumo Speakers Bureau Abbott Vascular, Asahi Intecc, Cook Medical, Cardiovascular Systems, Inc., Gore, Intact Vascular, Lake Region Medical, Medtronic, Mercator MedSystems, Penumbra, Philips/Volcano, Spectranetics, Terumo Grant/Research Support Boston Scientific, Cordis/Cardinal, Cook Medical, CloSys, Cardiovascular Systems, Inc., Daicchi Sankyo, Gore, Intact Vascular, Lake Region Medical, Medtronic, Mercator MedSystems, Penumbra, Philips/Volcano, Shockwave Medical, Spectranetics Figure 1. Arterial vasculature of the lower leg. A Tactical Approach to Arterial Access to Save Limbs The anatomy of the lower leg can be divided into three levels (Figure 1). The first is the inflow, or the illiac system. The second is the superficial femoral artery (SFA) and popliteal artery. The third is the area below-the-knee; specifically, the tibial and pedal anatomy. This article examines these three levels and offers tactical approaches to arterial access. Iliac Occlusions The investigation of a suspected iliac occlusion begins by accessing the contralateral femoral artery, placing a catheter at the level of the aorta, and then taking pictures. This allows the operator to see exactly what s happening in the vessel. If an iliac occlusion is diagnosed, the operator may attempt to cross up and over if it s not a flush occlusion at the level of the common iliac. However, sometimes support is lost during this approach. The following two access techniques are essential when treating a flush occlusion in cases that do not offer enough length to go up and over (Figure 2). The first technique is a brachial/radial approach, which is usually performed via the left arm instead of the right arm so it isn t necessary to traverse the great vessels. Approaching via the left arm also saves device length, because we lose length if 6 Supplement to Cath Lab Digest November 2018 Supplement to Cath Lab Digest November

5 A B A B Figure 5. Angiographic access into the popliteal artery (A, B). Figure 6. Angiographic access into the peroneal artery (A, B). Figure 2. Iliac crossing strategies: radial/brachial antegrade access and common femoral artery retrograde access. Figure 4. Popliteal access (A, B). we approach from the right arm. The brachial/radial approach offers a straight line into the iliac to provide support. The second access point for iliac occlusions is the common femoral artery on the same side as the lesion, such that the operator accesses the vessel from a retrograde approach to cross the iliac occlusion (Figure 2). One benefit of using the contralateral femoral approach with the retrograde CFA approach is that the operator can inject and see (especially with a flush occlusion) exactly where you would place the stent if you were coming from a retrograde femoral approach. Superficial Femoral Artery and Popliteal Occlusions The typical access choice for SFA and A Figure 3. Crossing strategies for superficial femoral artery and popliteal occlusions. popliteal occlusion intervention is a contralateral femoral approach. An antegrade CFA approach is preferable due to stability and support. However, this method requires enough room at the SFA to place the sheath. If it s a flush occlusion and this room isn t available, a different access technique is necessary (Figure 3). As with the iliac occlusions that were discussed above, the operator must therefore use a retrograde approach. There are a few different retrograde options. The first is a popliteal approach, wherein the patient is resting flat on his back and the needle is placed from the medial approach and sticks the popliteal artery. This is performed under direct visualization from above. Another option is to have the patient lie in a prone position and stick the popliteal artery directly from the back of the knee (Figures 4A and B). In this situation, the operator could come from a contralateral femoral approach and visualize from above, or they could opt for a radial/brachial approach to allow visualization from above, such that they could cross and treat from below. Tibial and Pedal Chronic Total Occlusions Posterior tibial access and retrograde access especially how to obtain tibial access angiographically are important topics to consider in the treatment of tibial and pedal chronic total occlusions. The presence of an ultrasonographer in the lab who is competent with guiding B tibial access is strongly recommended. This reduces dye and radiation during the procedure. However, most of the people in the world do not have access to an ultrasonographer who is competent with tibial guidance. Therefore, operators must be well versed in the angiographic techniques used to obtain tibial access, which are illustrated in the pedal access cases below. Case Example #1: Posterior Tibial Access To access the vessel angiographically during posterior tibial access, the operator must remember that the posterior tibial artery is medial. Therefore, when imaging the left leg, the operator would bring the camera into a right anterior oblique position set at about 20. The needle should be parallel to the angiography beam and perpendicular to the vessel. The operator begins with a fluoro-subtracted still image of the angiogram and then watches the screen in real time as the needle enters the vessel (Figures 5A and B). Sometimes the operator can feel the needle pop as it enters the vessel; an assistant alerts the operator when blood flow drips from the needle. Access is obtained in approximately 5 seconds, which indicates that angiographic access is just as quick as ultrasound access if these techniques are utilized. Typically, the posterior tibial is the most difficult to access with angiography because although it is a large vessel, it tends to move or roll off the needle. The peroneal is less difficult despite deep accessibility because it is held in place and offers identifiable landmarks such as the interosseous membrane. The anterior tibial is the easiest of the three because it is held in place and is superficial. Case Example #2: Peroneal Access As in Case Example #1, to obtain peroneal access, the operator begins with a fluoro-subtracted still frame of the angiogram so the path ahead is clear. This example accesses the left leg, so the camera is placed in a 20 left anterior oblique position to display the peroneal artery, which runs in between the tibia and fibula. The operator watches the screen (Figures 6A and 6B) as the micropuncture needle goes through a few identifiable landmarks and pops twice. The first pop indicates that the needle is through the interosseous membrane and the second pop is the needle entering the peroneal artery. In this case, it took less than 10 seconds to obtain peroneal access. It s important for operators to become well versed in these techniques using an angiographic approach, as it s very difficult to visualize the peroneal artery using intravascular ultrasound. Other Techniques There are two other access techniques that are important to learn. The first is the direct SFA stick, which is usually utilized for chronic total occlusions, where it s nice to have a stent in place. For example, in a case accessing the right leg, the operator rotates the camera medially, takes an 18-gauge needle, and directly sticks the stent. The operator will feel the needle go through the stent struts, at which point the camera is rotated 90 to visualize the depth of the needle. The operator then uses a stiff guidewire followed by a stiff catheter, such as the Navicross (Terumo), and comes through the occlusion from a retrograde approach and comes down from above. The way to hold tamponade to an SFA stick is to hold by internal tamponade. Once the operator successfully opens the vessel, a balloon is inflated internally against the puncture site for 2 to 3 minutes to stop the bleeding. A second approach is the pedal approach to access the digitals in between the web of the toes. The operator takes a micropuncture needle, sticks the digital, takes a hydrophilic wire (usually bare-back with a crossing catheter), and then flosses the wire and works from above. 8 Supplement to Cath Lab Digest November 2018 Supplement to Cath Lab Digest November

6 Lutonix DCB Global BTK Registry Study 12-Month Interim Outcomes: A Prospective, Multicenter, Single-Arm, Real-World Registry Investigating the Clinical Use and Safety of the Lutonix Drug-Coated Balloon PTA Catheter for Treatment of Below-the-Knee Arteries Marianne Brodmann, MD Medical University Graz, Graz, Austria Disclosures: Consultant Medtronic, Becton Dickinson (Bard)/Lutonix, Intact Vascular, Avinger, Limb Flow, and Philips (Spectranetics) Introduction The objective of the Lutonix below-theknee (BTK) study is to demonstrate the superior efficacy and non-inferior safety of the Lutonix drug-coated balloon (DCB) by direct comparison to standard percutaneous transluminal angioplasty (PTA) for the treatment of stenosis or occlusion of BTK arteries. The study is closed to enrollment, and the study population now includes 442 subjects. Figure 1. Study synopsis of the Lutonix DCB study. Study Overview A synopsis of the Lutonix BTK study design is shown in Figure 1. Briefly, this trial is the second-largest randomized controlled trial of patients with critical limb ischemia and BTK disease. This is a prospective, multicenter, single-blind, randomized safety and efficacy study. The objective is to demonstrate the superior efficacy and non-inferior safety of the Lutonix DCB dilatation catheter by direct comparison to standard PTA catheter for treatment of stenosis or occlusion of BTK arteries. Patients were randomized 2:1 to a Lutonix DCB or standard PTA catheter. The primary endpoints are shown in Figure 2 and inclusion and exclusion criteria are shown in Figure 3. Patient Demographics The following demographic information is currently available on the first 412 subjects. Mean patient age is 72.9 ± 9.72 years and males comprise 68.7% of the study population. The majority (79.1%) are white, while 0.2% are American Indian, 9.5% are Asian, 10.2% are African American, and 1% are other. Patient height and weight data are available for 410 patients. Mean patient height is ± 10.4 cm and weight is 82 ± kg. Mean body mass index (BMI) is 28.1 ± 6.01 kg/m 2 and 34.9% of patients have a BMI 30 kg/m 2. Figure 2. Primary endpoints of the Lutonix DCB study. Figure 3. Inclusion and exclusion criteria for the Lutonix DCB study. Medical History Medical history is available on 409 of the first 412 study subjects. Many patients (58.7%) are current or previous smokers, 69.7% have diabetes, 75.6% have dyslipidemia, and 91.9% have hypertension. Coronary artery disease is present in 49.1% and heart failure is present in 11%. History of myocardial infarction is reported in 21.3%, chronic obstructive pulmonary disease in 12.2%, osteomyelitis in 7.1%, and renal failure in 20.5%. Baseline Angiographic Data Baseline angiographic data are available for 389 patients unless otherwise noted. In this population, 75.6% had one lesion treated, 20.1% had two lesions treated, 3.6% had three lesions treated, and 0.8% had four lesions treated. The mean total target lesion length was ± mm (data available in 385 patients). The mean percent diameter stenosis was 88.2 ± 13.87%, and 44.5% had chronic total occlusions, which is quite high. The mean reference vessel diameter was 2.54 ± 0.57 mm. Most patients (61.7%) had some calcification, while 26.2% of the 237 patients with available data had severe calcification. The treated lesions were located in the popliteal artery in 11.1%, tibioperoneal trunk in 30.1%, anterior tibial in 44.2%, posterior tibial in 27.5%, and peroneal artery in 26.2% of patients. Some patients had more than one vessel treated. Preliminary Rutherford Classification In the first 412 randomized subjects, 8.3% have baseline Rutherford class 3, 35.8% have class 4, and 56.0% have class 5 peripheral arterial disease. Based on a Rutherford classification of 4 or 5, a total of 91.7% have critical limb ischemia. Lutonix BTK Update The Lutonix BTK study is now closed to enrollment. We currently have 49 active global sites (United States, 30; Europe/ Canada, 13; Japan, 5; Australia, 1). At this point, the study has enrolled 442 randomized subjects, and 17 (3.8%) have had a major amputation; this rate is very low. The Data Monitoring Committee (DMC) has now met 16 times over the course of the study and unanimously recommended continuation of the study with no modifications. Some DCB trials, and in particular one large trial on BTK vessels, have shown the failure of DCBs. The promising results of the Lutonix DCB trial at 12 months indicate it might be a milestone trial to address the usage of DCBs in BTK arteries. Summary The primary endpoints of the Lutonix DCB study are safety at 30 days and limb salvage and primary patency at 6 months. In the current study population, 91.7% of patients have CLI, 56% have Rutherford class 5 lesions, 69.7% are diabetic, and 31.3% are females. The major amputation rate of 3.8% is very low at this point. The study has been strictly monitored by the DMC, which has deemed the study safe to continue with no modifications to the protocol. 10 Supplement to Cath Lab Digest November 2018 Supplement to Cath Lab Digest November

7 Build a CLI Program in 1 Year: It s Not Impossible Paul Michael, MD, FSCAI Medical Director, JFK Wound Management and Limb Preservation Center, Atlantis, Florida Disclosures: Consultant Abbott Vascular, Boston Scientific, Medtronic A B C D Figure 1. The first multi-specialty team to tackle CLI formed 3,000 years ago in Egypt (A). CT confirmation of atherosclerosis in the distal digital vessels, which was treated with partial amputation (B, C) and fully functioning prosthesis so this patient was able to continue walking for another 20 years (D). (Originally published in CLI Global). Introduction Last year, I attended every single lecture at the AMP Symposium. It was the best academic meeting I ve ever attended. The #1 message I took from the meeting was not about fancy tools or revascularization; it was about how to build a team. As I ve learned more about angioplasty and critical limb ischemia (CLI), I ve realized that when you are out there alone, you aren t going to be able to treat the patients you want to treat. The only way to do it is to put a team together. My disclosures are: I LOVE LEGS I HATE AMPUTATION I WORK IN FLORIDA Background CLI represents the end stage of peripheral arterial disease. The US economic impact of CLI is in the billions of dollars, and 2-year mortality rates after CLI diagnosis are approximately 40%. The cornerstone of CLI treatment is not cosmetic angioplasty it is wound healing. The people who do wound healing day in and day out understand that advanced wound management has to complement revascularization in order to preserve function, prevent limb loss, and improve cardiovascular health. Non-invasive evaluation of CLI is inaccurate and shockingly, amputation without a vascular workup is still practiced. My message today is that integrated multi-specialty CLI teams save limbs and lives, and it is possible to create a CLI team anywhere in the US. 3,000 Years Ago... The first multi-specialty team to tackle CLI formed 3,000 years ago in Egypt. Computed tomography (CT) confirmation of atherosclerosis in distal digital vessels was treated with partial amputation and fully functioning prosthesis so this patient was able to continue walking for another 20 years (Figure 1). The American College of Cardiology/American Heart Association guidelines (Figure 2) 1 for the management of patients with lower extremity peripheral artery disease can be summarized as follows: revascularization to minimize tissue loss performed by an interdisciplinary care team to provide comprehensive care and complete wound healing. This summary became our motto when we built our own CLI team. How Do You Build a CLI Team? Start Somewhere! 1 Person can make a difference in the team-building process 1 Article can change your career 1 Meeting can light the way 1 Mentor can show you the path 1 Patient can change the way an entire hospital views amputation prevention 1 Team can change a community and support an amputation prevention program 1 Goal: to say No! to amputation DREAM: Docs Revascularizing Extremities Against Major Amputation We put together the DREAM program 2 with the simple concept that a community of physicians could get together, irrespective of their affiliations and skill levels, in pursuit of the following common goals: To promote CLI awareness Figure 2. Summary from the American College of Cardiology/American Heart Association guidelines for the management of patients with lower extremity peripheral artery disease (top). Recommendations for revascularization with critical limb ischemia (CLI) (bottom). Recommendations for wound healing therapies for CLI. Figure 3. Patient with advanced CLI. To ensure angiography prior to amputation To adopt an early invasive strategy for CLI To achieve wound-directed therapy To ensure multi-disciplinary care To close the gap on amputation disparities Early Invasive Strategy for CLI We had to get the hospital to understand that CLI is to PAD what ACS is to CAD. We don t stress people in the emergency room we take them to the cath lab. We don t do ultrasounds on hot feet; we get a Doppler machine and bring the patient to the cath lab as fast as possible. The wait times to treatment were abysmal at our hospital before we put a team together. Vascular evaluation is always part of the process, but we don t let it hinder taking the patient to the cath lab to take a picture of the leg. Create Awareness and Build the Team As soon as we left the AMP Symposium last year, we decided to go back to the drawing board and create our own CLI team. First, we offered continuing medical education dinner presentations to physicians, residents, and hospital staff to educate them on our new multi-disciplinary approach to CLI and amputation prevention. We also offered different specialists the opportunity to participate in medical grand rounds; for example, we had podiatry residents doing angioplasty using the TAMI technique and retrograde pedal access. In addition, we initiated community outreach programs to educate potential patients on the symptoms and risks of CLI. Advanced Wound Care Advanced wound care must complement revascularization. We have to show the community, the hospital, and the patients what we are actually accomplishing. The goal is wound healing. We must educate the community on the importance of tibial-pedal reconstruction. Troisi et al 3 researched pedal arch status and determined that it has a positive impact on time to healing, limb salvage, and survival in diabetic patients with foot wounds undergoing infrainguinal endovascular revascularization. Their study reinforces the idea that we must focus on tibial-pedal reconstruction to help each patient s wound(s) heal quickly. Impact of a Community CLI Team The CLI team concept is out there and has been presented before by other authors. Why aren t we pursuing the team approach? The biggest disparity in amputation rates in the US is not between races or socioeconomic class, it s between those who have access to a CLI team and those who do not. We don t have enough teams to take care of this disease burden. Why don t we have enough centers of excellence for CLI treatment? The DREAM CLI Team Concept Collaboration over competition is the first hurdle to creating an effective team. Conservative care on the front end and highly aggressive prevention with preservation on the back end are the keys to major amputation prevention. The DREAM CLI Team Multi-Disciplinary Formula Our formula for success involves the following factors involving multiple disciplines. This approach relies upon advanced tibiopedal reconstruction with arterial and venous workups to complete wound management. In addition, alternative access 12 Supplement to Cath Lab Digest November 2018 Supplement to Cath Lab Digest November

8 References 1. Gerhard-Herman MD, Gornik HL, Barrett C, et al AHA/ ACC guideline on the management of patients with lower extremity peripheral artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2016;135:e726 e Michael P. DREAM: docs revascularizing extremities against major amputation. CLI Global Troisi N, Turini F, Chisci E, et al. Impact of pedal arch patency on tissue loss and time to healing in diabetic patients with foot wounds undergoing infrainguinal endovascular revascularization. Korean J Radiol. 2018;19: Figure 4. Examples of foot and ankle trauma reconstruction performed by our CLI team. Figure 5. Examples of patients with chronic venous disease. must be standardized, so that it s no longer alternative. Multi-segment, multi-vessel chronic total occlusions are the norm for us, and we must be very comfortable with treating these rapidly. Advanced foot and ankle reconstructive surgery with vascular surgery integration are also integral to this team approach. Finally, advanced wound care (with specialized wound EMR) is essential to the DREAM formula. CLI patients are usually Rutherford class V and VI (and sometimes class IV), such as the patient in Figure 3. I d like to expand on that and show a few examples of what CLI teams can do. We are regularly scheduled to take care of major amputation patients, and it has become the norm for us to deal with zero-contrast CLI cases in those with chronic kidney disease. A high volume of foot and ankle trauma reconstruction, as demonstrated in Figure 4, has become a subset of patients at our institution. These are complex patients who once had no options. Because we have a tibial-pedal reconstruction program, we work with foot and ankle specialists to complete these procedures. Chronic venous disease (Figure 5) is also treated by our team. Make no mistake, this is another face of limb salvage. What is the Impact of a Community CLI Team? The following factors all decrease after the implementation of a CLI team: Time to appropriate consultation Time to vascular workup Time to angiography Time to therapy delivery Time to discharge Time to ambulation Wound healing time Amputation and healthcare costs Mortality rate How Do We Convince Our Hospitals to Implement CLI Teams? Instead of telling our hospital systems and communities about the benefits of a CLI team, we show them our results. Social media has been an incredible education tool. Hashtags such as #drsavealimb, #showusyourteam, #mylegmylife, and #CLIfighters have helped the CLI fighters spread community awareness. Get a Mentor A mentor is critical to the development of a CLI team. This is not an easy process, and a mentor can help guide you through each obstacle. There is no need to re-invent the wheel. The DREAM Program Figure 6 shows the components necessary to make the DREAM program work. Four major groups (hospitals, physicians, patients, and payers) are integrated to get the job done. Multi-disciplinary wound management supports cost-effective, data-driven results, and these results align the community, which is all driven by CLI awareness. The groups of people represented in this figure do not all belong to the same specialty. They are not hospital employees; they are individuals working through a single wound-management center that is affiliated with the hospital. Teamwork Makes the DREAM Work Specialty agnostic belief in CLI therapy produces collaboration between different specialties in the community, such as the following patient who was refered to us by Dr. Daniel Elgut, DPM, Foot and Ankle Surgeon. In an example of the results that can occur with collaboration between specialties, this 31-yearold drive-by shooting victim with multiple gunshot wounds to the leg (Figure 7) was a very atypical limb salvage case, with multiple pseudoaneurysms and complex anatomy in the foot. A complex pseudoaneurysm in the superficial femoral artery was present, with a potential space being fed by three vascular sources; this procedure was guided by the angiographic knowledge of somebody who spends every day treating the pedal vessels. Figure 8 shows the final angiographic result, and the three specialists working together to save this young man s leg. This case is an example of the immense potential of the CLI team to effectively treat complex patients under a variety of circumstances. Figure 6. The DREAM program. Figure 7. A 31-year-old drive-by shooting victim with multiple gunshot wounds to the leg. Multiple pseudoaneurysms and complex anatomy of the foot are apparent. Figure 8. Final result of the gunshot victim showing patency in the pedal loop (left). Dr. Daniel Elgut, DPM, Dr. Brad Lind, DPM, Dr. Jack Zeltzer, MD, Vascular Surgeon, and Dr. Paul Michael, MD, Interventional Cardiologist, work as a team to save the young man s leg (right). 14 Supplement to Cath Lab Digest November 2018 Supplement to Cath Lab Digest November

9 Plaque Morphology From A to Z and PRIME Registry CTOP Analysis Fadi Saab, MD, FAGG, FSCAI, FASE Associate Professor of Medicine, Michigan State University School of Medicine Advanced Cardiac & Vascular Amputation Prevention Centers, Grand Rapids, Michigan Disclosures: Consultant Bard Peripheral Vascular/Lutonix, Boston Scientific, Cardioflow, Cardiovascular Systems, Inc., Medtronic, Philips, Reflow Medical, and Terumo Medical Figure 1. Planning a CTO crossing strategy. Stating the Problem Chronic total occlusions (CTOs) are very common when it comes to peripheral vascular disease, especially in critical limb ischemia (CLI) patients, ranging anywhere from 50%-60% within the PRIME registry, which is a multicenter observational registry with 3-year follow-up. PRIME registry patients are in Rutherford class 3-6 and have undergone peripheral vascular interven-tion. The first subject was enrolled in January of 2013, and currently, there are >900 subjects enrolled at five centers. Failure rates in crossing CTOs have ranged from 20% to 40% in some instances. Most opera-tors do not attempt retrograde tibiopedal access unless a traditional attempt to cross the CTO in antegrade fashion has already been pursued. This traditional approach provides a false sense of security and could arguably be harmful in some instances, given that after a failed antegrade attempt most physicians tend to stop and reschedule the patient for another procedure. This predisposes the patient to another hospitalization, puncture, potential exposure to anesthesia, and other inherent complications. This year, my colleagues and I were privileged to publish the findings of the CTOP trial, 1 which was an ongoing project for 3 years that was published in February of CTOP is a retrospective analysis that evaluated CTO cap morphology and assessed its ability to predict successful lesion crossing. This trial analyzed 142 CTOs in 114 patients enrolled in the PRIME registry. The CTOP trial examined the prevalence of different CTO caps, as well as access selection, techniques used, and success rates of crossing CTO lesions. Past efforts to cross CTOs using a try it and see if it works strategy were often frustrating to operators. The thought process behind planning a CTO crossing strategy (Figure 1) is often complex and requires looking at the proximal and distal caps, determining access selection and crossing strategy, and choosing an appropriate revascularization strategy. Our team therefore mapped out CTO plaque caps and created the CTOP classification system (Figure 2) to guide access selection. CTOP stratifies cap morphology into Types I-IV. The least common type of cap morphology is Type III (14%) which is fortunate since it s the most challenging to cross followed in frequency by Type I (20%), Type IV (29.4%), and Type II (36.6%). Figure 3 demonstrates the CTOP lesion types with the likely path of the wire represented by a yellow arrow. In Type I Table 1. CTO distribution. Table 2. Access data. Table 3. Lesion characteristics. lesions, the wire should be able to cross in an antegrade fashion. In Type II, the wire will be deflected distally, necessitating retrograde access to meet in the middle. As mentioned, Type III is the most challenging; this is because the wire will be deflected at both caps and will require more advanced strategies. In Type IV, the wire usually requires crossing in a retrograde fashion. The CTO distribution results from our trial are shown in Table 1. 1 Overall, 30%- 35% of CTOs were within the tibial circulation. The access data (Table 2) show that we converted to tibial access (as opposed to planned tibial access) in about 25% of the overall cases. Table 3 shows the lesion characteristics. If we examine the calcium density, we see that about 50% of the lesions in the study population were classified as severe calcification. Interestingly, when we examine the lesion length, we find an overall average length of mm, with the shortest lesions classified as Type I. When we examined the frequency of crossing techniques, we found that 37% of CTOs were crossed in an antegrade fashion, 22.6% were crossed in a retrograde fashion, and 40.1% required advanced techniques. Univariate analysis of several factors (CTOP Type I, II, III, IV, or II/III, lesion length >10 cm, severe calcium density, diabetes, chronic kidney disease, critical limb ischemia, and below-the-knee vessel location) showed that the highest predictor of crossing in an antegrade fashion was a Type I lesion, while the highest predictor of crossing in a retrograde fashion was a Type IV lesion. We also performed a univariate analysis with the same variables as above, along with a multivariate analysis including severe calcium density and lesion length, to predict access conversion. The greatest predictors of conversion were Type II and III lesions, lesion length >10 cm, and severe calcification. Thus, we created a straightforward algorithm (Figure 4) to determine the most appropriate access strategies for different CTO types. Short (<10 cm), non-severely calcified CTOs can be treated with antegrade crossing, while long (>10 cm), severely calcified CTOs should 16 Supplement to Cath Lab Digest November 2018 Supplement to Cath Lab Digest November

10 be classified using CTOP, with the algorithm then used to determine whether retrograde or alternative access would be recommended. Figure 2. The CTOP classification system and the frequency of each lesion type. Figure 3. CTOP lesion types. The yellow arrows represent the likely path of the wire traveling through the lesions. Figure 4. CTO access algorithm to determine the most appropriate access strategies for different CTO types. Case Example #1 An 80-year-old male with multiple risk factors (hypertension, hyperlipidemia, OM c/b neuropathy, CAID status post coronary artery bypass graft surgery, 5.7 cm infrarenal abdominal aortic aneurysm) presented with Rutherford class 4 right leg CLI and symptoms of bilateral rest pain. His left leg symptoms had resolved with recent left posterior tibial revascularization, but his right-sided symptoms persisted. Diagnostic angiography (Figure 5) indicated the patient had a Type IV CTO. We obtained access using a modified Schmidt technique in an occluded posterior tibial artery under ultrasound guidance; it was apparent there was no flow in this vessel. I ignored my own rules and tried to access antegrade and created a small microperforation; subsequent angiography showed extravasation. We then crossed the CTO in a retrograde fashion and used a tunneling technique (Figure 6), wherein an 018 CXI catheter and 014 Command wire were fed antegrade into an 035 Navicross catheter. We finally delivered therapy using intravascular ultrasound (IVUS)-guided intervention, laser atherectomy with a 0.9 mm device, and percutaneous transluminal angioplasty with a 3.5 mm balloon (tibioperoneal trunk and posterior tibial) and a 5 mm balloon (popliteal and proximal tibioperoneal trunk). The final result was excellent, with pedal loop reconstruction (Figure 7). Case Example #2 A 73-year-old female presented with Rutherford class 5 CLI (Figure 8) and angiosome distribution corresponding to the right anterior tibial artery. She had undergone common femoral artery (CFA) endarterectomy 3 weeks prior (Figure 9) and was referred by vascular surgery for more distal tibial therapy. We examined the posterior cap of the anterior tibial artery CTO on angiography (Figure 10), which showed a CTOP Type II cap morphology; this is a common CTO pattern in the anterior tibial Figure 5. Case Example #1: Diagnostic angiography of an 80-year-old male with multiple comorbidities showed a Type IV CTO. Figure 6. Case Example #1: The tunneling technique using an 018 CXI catheter and 014 Command wire fed antegrade into an 035 Navicross catheter. Figure 7. Case Example #1: Excellent final result with pedal loop reconstruction. Figure 8. Case Example #2: A 73-year-old female presented with Rutherford class 5 critical limb ischemia. Figure 9. Case Example #2: The patient underwent common femoral artery endarterectomy 3 weeks prior to this intervention. artery, and the reconstitution into the dorsalis pedis artery was apparent. We ask ourselves the following types of question on a daily basis when performing this type of intervention: Which vessel should we access? Is it possible to perform antegrade access? Should we use a CTO device? What size sheath? CTO wire vs workhorse wire? Should we start with antegrade crossing? If failed... Bring back? Start with pedal access? We decided to prepare for pedal access. Ultrasound-guided access was performed beyond the endarterectomy site using a triaxial system (4-F sheath, 018 wire, Supplement to Cath Lab Digest November 2018 Supplement to Cath Lab Digest November

11 Figure 10. Case Example #2: CTO cap morphology on angiography was classified as a CTOP Type II. Figure 11. Case Example #2: The loop on the wire was not unreasonable, and we thought we had crossed into the dorsalis pedis artery. Figure 12. Case Example #2: Ultrasound confirmed that the wire had moved subintimally. catheter) that was advanced under fluoroscopic guidance. Figure 11 demonstrates that the loop on the wire was not unreasonable, and we thought we had crossed into the dorsalis pedis artery. In reality, however, ultrasound (Figure 12) confirmed that the wire had moved subintimally. We obtained retrograde tibiopedal access and advanced an 018 to the 018 wire, easily passed the CTO cap, and ultimately delivered therapy, resulting in an excellent final result for this patient. Note that the time from access to tunneling took approximately 3 minutes and 45 seconds, while the time to access to the subintimal took 6 minutes and 36 seconds. If you think retrograde access makes the case longer, think again! Conclusion CTOP is the first trial to categorize CTOs in a simple, easy to apply process. Lesion length, calcium content, and CTO types II and Ill are the major predictors of access conversion. The implications for technical success are significant, exceeding 98% of cases. There are potential time savings and an increase in safety profile. Starting with pedal access may potentially be the standard of care as experience is gained among operators. Reference 1. Saab F, Jaff MR, Diaz-Sandoval LJ, Engen GD, McGoff TN, Adams G, Al-Dadah A, Goodney PP, Khawaja F, Mustapha JA. Chronic total occlusion crossing approach based on plaque cap morphology: the CTOP classification. J Endovasc Ther. 2018;25(3): doi: / Epub 2018 Feb 27. Claims Analysis Summary on CLI Mortality and Morbidity Presented on behalf of the CLI Global Society Board Members Jihad A. Mustapha, MD Advanced Cardiac & Vascular Amputation Prevention Centers Grand Rapids, Michigan Disclosures: Consultant Abbott Vascular, Bard Peripheral Vascular, Boston Scientific, Cagent Vascular, Cardioflow, Cardiovascular Systems, Inc., Corindus, Medtronic, Micromedical Solutions, Philips/Spectranetics, PQ Bypass, Reflow Medical, Terumo Major Stock Shareholder Cardioflow Table 1. Baseline Patient Characteristics. Characteristic Value (N = 72,199) Region at diagnosis South 42% Midwest 24% Northeast 20% West 13% Population density at diagnosis Urban 89% Rural 11% Demographics Male sex 52% Age (years) 74 ± 12 Race White 76% Black 19% Other 5% Medical history Hypertension 73% Diabetes mellitus 54% Coronary artery disease 48% Chronic kidney disease 33% Hyperlipidemia 27% Tobacco use 20% Clinical presentation Rest pain (ICD-9-CM ) 29% Ulcer (ICD-9-CM ) 45% Gangrene (ICD-9-CM ) 25% Background No large-scale study has previously defined the long-term fate of patients following initial critical limb ischemia (CLI) diagnosis. The purpose of this study was to describe long-term clinical outcomes in Medicare beneficiaries following initial CLI diagnosis. 1 Study Population The study population consisted of 72,199 adult Medicare beneficiaries with a first-time CLI diagnosis arising from inpatient or outpatient care at a participating hospital. Unfortunately, many of these CLI cases were not found due to patient awareness of CLI symptoms or CLI screening; rather, they were discovered when it was almost too late. CLI Diagnosis CLI diagnosis is defined as the date of first claim with primary ICD-9 diagnosis of atherosclerosis of native arteries of the extremities with: (1) rest pain (ICD-9-CM code, ); (2) ulceration (ICD-9-CM code, ); or (3) gangrene (ICD-9- CM code, ). Note that ICD-9-CM codes are presented here; we had hoped to do a 5-year analysis, but were unable to do so because the codes were changed to ICD-10-CM in the United States at the 4-year period. It is, however, important to pay attention to the three different diagnoses, because the stage at which the patient presents does make a difference in terms of their long-term outcome. Patient Inclusion Criteria This study included patients with a date of CLI diagnosis from January 1, 2011 to December 31, In addition, the patients required continuous Medicare coverage from January 1, 2010 to January 31, Patients were only included if they had no CLI diagnosis code in Patients were followed through September 30, Note that the dates correspond to the date of the transition from ICD-9-CM to ICD-10- CM; therefore, this study was stopped at 4 years. 20 Supplement to Cath Lab Digest November 2018 Supplement to Cath Lab Digest November

12 Figure 1. Survival through 4 years by clinical severity. Patients who presented with rest pain did better than those who presented with ulceration, and patients with ulceration did better than those with gangrene. Earlier diagnosis is the key to improving survival rates. Figure 2. Freedom from major amputation through 4 years by clinical severity presentation. Baseline Patient Characteristics The baseline patient characteristics are shown in Table 1. When patients were stratified according to United States region at diagnosis, we found that 42% of patients lived in the South, 24% lived in the Midwest, 20% lived in the Northeast, and 13% lived in the West. In addition, note that 89% of patients lived in an area with an urban population density, while 11% lived in a rural area. The study population consisted of 52% males, with a mean age of 74 ± 12 years. The breakdown of patients by race was 76% white, 19% black, and 5% other. We found that a medical history of hypertension (73%) was very common in the study patients. Medical history also included diabetes mellitus in 54%, coronary artery disease in 48%, and hyper-lipidemia in 27% of patients. Notably, history of chronic kidney disease (CKD) was present in 33%; the medical community must pay attention to CKD in their CLI patients as much as they do in their diabetic patients. When we stratify the patients by ICD-9-CM codes for clinical presentation, we find 29% with rest pain, 45% with ulcer, and 25% with gangrene. These are serious numbers that equate to a bad outcome. When we examine the survival curves through 4 years by clinical severity based on initial presentation (Figure 1), we see that patients who presented with rest pain did better than those who presented with ulceration, and ulceration did better than gangrene, as one would expect. If we can catch these patients earlier, the survivor function estimate will improve. We must find a better way to increase awareness of CLI symptoms and a better way to diagnose patients in the earlier stages of this disease. Figure 2 shows the survival curve for freedom from major amputation through 4 years by clinical severity presentation. These curves again show that gangrene patients have worse survivor function estimates than ulceration, which is worse than rest pain. These results reinforce the need to educate CLI patients and catch these patients earlier in their disease progression. Based on these data, when a patient presents with gangrenous toes or a gangrenous forefoot, we must treat them far more aggressively than we have in the past. Overall Patient Status After CLI Diagnosis The data on the overall patient status post-diagnosis are mindboggling: at 4 years, 54% of the patients have died, 3% are alive with major amputation, and 42% are alive and free from major amputation (Figure 3). These are serious real-world findings that correspond to rates for any other major disease. To put this into perspective, at 54%, the 4-year mortality rate for CLI is higher than the mortality rates of most cancers. 1 According to the National Cancer Institute, 2 the 5-year mortality rate is 53% for ovarian cancer, 50% for myeloma, 39% for leukemia, 35% for colorectal cancer, and 10% for breast cancer. It is clearly time for us to step up and find these patients earlier and treat them as soon as possible. Amputation is not a therapy amputation signals the end of that patient s life within the next year or so. We must consider the following questions: Are we doing CLI trials properly today? Is it fair to say that if we have an advanced CLI patient, we should randomize them, or is it time for us to think outside the box and do things differently? Just Do Something! Prompt revascularization by endovascular or open surgical procedures should be considered following CLI diagnosis to minimize tissue loss and preserve ambulatory function. Those who ambulate earlier do better and maintain a better quality of life, which was seen in the present study as well as in other trials that were presented at AMP Overall Survival in a Matched Subset Figure 4 shows the overall survival rates for surgical revascularization versus endovascular revascularization. The two dashed survival curves illustrate that it doesn t matter which therapy we use for our patients; the results are the same, and they are Figure 3. Overall patient status through 4 years after CLI diagnosis. Figure 4. Overall survival rates for a matched subset of surgical revascularization versus endovascular revascularization. The two dashed survival curves illustrate that it doesn t matter which therapy we use for our patients; the results are the same. The solid survival curve shows the results when we do nothing and perform above-ankle amputation. beneficial. If we do nothing and perform above-ankle amputation, the outcome is worse and the mortality rate is much higher, as shown in the solid survival curve. It is important to use a multidisciplinary approach and to be aggressive with treatment. Conclusions Patients with CLI have poor long-term prognoses following initial diagnosis. However, as Figure 4 demonstrated, we can do something for the worst cohort of patients and prolong their lives and we can help them. We can no longer say that CLI is a disease without any treatment options. The present study1 and others have shown the benefit of therapy to these patients. Through 4 years, only 42% were alive and free from major amputation but we must ask, what happened to the other 58%? This study included patients from a Medicare database of real-world patients, so there was no biased selection. We see these patients every day. I urge everyone to work together to help raise awareness of these voiceless, dying patients. This community has various backgrounds and different levels of experience and education, but we all took the same oath to do what is best for patients in need. We know that based on clear scientific evidence, we can help them not only save their legs, but also save their lives. References 1. Mustapha JA, Katzen BT, Neville RF, et al. Disease burden and clinical outcomes following initial diagnosis of critical limb ischemia in the Medicare population. JACC Cardiovasc Interv. 2018;11: National Cancer Institute. Cancer Stat Facts. Available at Accessed August 27, Supplement to Cath Lab Digest November 2018 Supplement to Cath Lab Digest November

13 Are All CLI Cases Created Equal? Thomas Davis, MD, FACC St. John Hospital, Eastlake Cardiovascular, Roseville, Michigan Disclosures: Abbott, CSI, Boston Scientific, Philips Medtronic, Avinger, BTG, Micromedical renal failure, severely decreased cardiac output (severe heart failure or shock), vasospastic diseases or concomitant conditions, such as Raynaud s phenomenon or prolonged cold exposure, and smoking and tobacco use. Factors that increase demand for blood flow to the microvascular bed include infection (eg, cellulitis or osteomyelitis), skin breakdown, or traumatic injury. a All of these things create similar problems, but use different mechanisms that we must contend with. Patient Presents with CLI: What Do We Do Next? Patients present with varying degrees of wounds, and the wounds may appear on different aspects of the foot (Figure 2). The wounds can be caused by trauma or skin breakdown, or may be self-inflicted. We know our complex patients can have multiple comorbidities with similar and often overlapping signs and symptoms. Are we looking for all contributing factors? Patients clinically present differently. In some cases, such as the patient in Figure 3, it may be necessary to discover whether the foot is viable or not before we can attempt revascularization. Figure 2. Three patient examples with severe CLI. Figure 3. A foot with severe CLI: Is the foot still viable? R4 Rest pain Revasc ATK +/- BTK CLI patients typically have multilevel and multivessel disease, which requires the performance of multiple procedures in both lower extremities to establish direct in-line blood flow to the feet in patients with ulcers. Thus, we can be met with situations as varied as aortic disease (Figure 5) or multilevel, iliac, common femoral, superficial femoral artery disease (Figure 6), but one similarity in CLI patients is that we re almost always dealing with the infrapopliteal artery (Figure 7). Endovascular CLI Strategy R5 Minor loss Revasc ATK +/- BTK In fact, the vast majority of CLI patients have some form of infrapopliteal disease to go along with their multivessel disease, so we must be experts at dealing with all levels of disease. Patients have varying anatomical differences. We forget this at times because we are so used to treating the typical patient. Knowledge of the collateral circulation is a must. Cases have come up at our institution where the operator had to go through the transcollaterals, and so we must know R6 Major loss Revasc ATK +/- BTK Figure 1. Medical complications from obesity. What is a CLI Case, and How Are They Similar and Different? CLI patients are similar in that they all have a lot of chronic problems. They may have obesity (Figure 1), or they may be frail. They may have varying degrees of renal failure, peripheral vascular disease, cardiovascular disease, heart failure, diastolic dysfunction, etc. So, no two CLI patients are completely the same. We must remember that we aren t just technicians opening up blood vessels; we are physicians, too. And to really provide excellent patient care, we must treat them medically, too. Factors That Increase Risk of Limb Loss in Patients with CLI Factors that reduce blood flow to the microvascular bed include diabetes, severe Endovascular CLI Strategy Depends Upon Patient Presentation CLI patients are stratified into Rutherford class 4, 5, and 6; each class has varying degrees of amputation risk. Different algorithms, such as the one shown in Figure 4, exist regarding the proper treatment course for various patient groups. In other words, we typically have below-the-knee disease, but we have to decide if we want 1-, 2-, or 3-vessel runoff to that foot, which will vary based on the Rutherford class as well as on the location of the wound. Open single appropriate angiosome Early definitive foot surgery and skin closure before restenosis Able to open boundary angiosome only Close follow-up KIV Bypass Open multiple tibials especially if high risk Consider early bypass if wound deteriorates or unable to open angiosome Figure 4. A flow chart of endovascular strategy based on patient presentation. R = Rutherford CLI classification. Wound across 2 angiosomes Renal failure Incomplete plantar arch Large wound burden eg TMA Non-ambulatory status High surgical risk Adapted from Peter Schneider, MD a Also see Table 5 of Hirsch AT, et al. J Am Coll Cardiol. 2006;47:e1-e192.] 24 Supplement to Cath Lab Digest November 2018 Supplement to Cath Lab Digest November

14 A B Figure 10. Angiography in a CKD patient showed very sluggish flow coming down through the leg, with either outflow obstruction or possible cardiac output problems (A). Angiography further down the leg showed occlusion in the pedal branch, as well as in the posterior tibial and peroneal arteries (B). The tibial loop is opened; technically, the procedure is successful, but there is potential need for future amputation because there is no outflow in the very distal beds (C, D). C D Figure 5. Example of aortic disease. Figure 6. Example of multilevel, iliac, common femoral, and superficial femoral artery disease. Figure 7. Example of infrapopliteal artery disease. A B Figure 11. (A-F) Example of a case complicated by prior bypass and percutaneous procedures. This patient had a femorotibial bypass to the posterior tibial artery, necessitating an intervention through the bypass graft itself. The initial graft itself was successful, but the outflow was insufficient. C Figure 12. (A,B) A patient presented with total occlusion of the superficial femoral-popliteal artery. (C,D) The posterior tibial artery was patent through a posterior communicating vessel. D Figure 8. Anatomical variations of the popliteal tibial peroneal trunk. these variations. Figure 8 is a diagram of different anatomical variations of the popliteal tibial peroneal trunk. When these vessels are occluded, we must understand that these possibilities exist, so the operator might be able to perform the procedure via antegrade access, or might be forced to come retrograde because they can t see the origin of the vessel. Using the collateral circulation is ultimately important in some, but not all, patients. Operators must have knowledge about going through posterior and anterior communicating vessels, such as the Figure 9. Example of collateral circulation showing posterior and anterior communicating vessels. ones shown in Figure 9, to ensure an excellent result. Many CLI patients do have similarities when it comes to the collateral circulation. Chronic kidney disease (CKD) leads to an accelerated arterial wall calcification through a complex inflammatory response and an upregulation of osteoblastic differentiation. 1 The result is an increase in distal outflow obstruction. Hence, we see severe calcification and digital calcification in CKD patients. These patients are extremely challenging. For example, angiography in one CKD patient showed very sluggish flow coming down through the leg, with either outflow obstruction or possibly cardiac output problems (Figures 10A and 10B). As we came down through the anterior tibial (Figure 10C), we discovered it was the pedal branch that was actually occluded, along with the posterior tibial and peroneal arteries. We wired this area and came up around the loop and into the posterior tibial, and hoped to balloon the tibial loop, which is very important; however, as we can see in Figure 10D, even if we open up the tibial loop, we may either cause problems to the distal outflow, or we might have no outflow. Thus, even though we can say we technically performed a successful intervention, we might still have problems with this patient needing amputation in the future because there is no outflow in the very distal beds. Many cases are complicated by prior bypass and percutaneous procedures. Figure 11 shows a patient who had a femorotibial bypass to the posterior tibial artery. The graft was successful, but the outflow was insufficient. We therefore had to go through the bypass graft itself to creatively come up with another way of treating this patient. Multilevel disease is common; procedural planning and the ability to change the plan intraprocedurally is extremely important. For example, Figures 12A and 12B show a patient with total occlusion of the superficial femoral-popliteal. Once we broke through into the peroneal and this has been stressed many times at this year s AMP Symposium we obtained images as distally as possible so we could see exactly what we were dealing with in this patient. We could see he had a posterior tibial that was patent through a posterior communicating vessel (Figures 12C and D). We treated the superficial femoral-popliteal and into the peroneal, and we then had to decide intraprocedurally whether to do a posterior tibial stick and go upward to complete this procedure. So, Are All CLI Cases Created Equal? Quite simply No! Operators must be proficient and master a highly refined set of skills (retrograde tibial pedal access, ultrasound-guided access and interventions, antegrade CFA access, use of the different available devices to cross and treat these long occlusions, etc.) in order to achieve successful clinical outcomes. Not all CLI cases are created equally, and not all CLI operators are created equally. We all have different skill sets and knowledge bases, and meetings such as the AMP Symposium, NCVH, and ISET are important ways to gain more knowledge and to share our knowledge with others. Reference 1. Purnomo E, Emoto N, Nugrahaningsih DA, et al. Glycosaminoglycan overproduction in the aorta increases aortic calcification in murine chronic kidney disease. J Am Heart Assoc. 2013;2:e Supplement to Cath Lab Digest November 2018 Supplement to Cath Lab Digest November

15 Data-Driven vs. Policy-Driven Decisions for DCB Therapy Craig Walker, MD Clinical Professor of Medicine, Tulane Medical School and LSU School of Medicine, New Orleans, Louisiana; Founder, President, and Medical Director, Cardiovascular Institute of the South, Houma, Louisiana; Clinical Editor, Vascular Disease Management, Global Vascular Digest Disclosures: Consultant Abbott, Boston Scientific, Cardiva, CR Bard, Lake Regional Medical, Medtronic, Philips Volcano Speakers Bureau Abbott, Bard, Bristol-Myers-Squibb/Sanofi, Cardiva, Janssen, Philips/Volcano, W.L. Gore Major Stock Shareholder Cardiva PVD Training Abbott, Bard, Boston Scientific, Philips/Volcano Figure 1. Current FDA-approved drug-coated balloon systems. Introduction In America, we currently have three approved drug-coated balloon (DCB) platforms (Figure 1): the Lutonix DCB (Bard), the In.Pact DCB (Medtronic), and the Stellarex DCB (Spectranetics). Each of these utilizes paclitaxel in some way, shape, or form along with a different form of excipient. Is One DCB Better Than Another? The three DCBs have been studied extensively; however, there are no direct comparison data yet available. Therefore, no one can definitively claim that one is more effective or safer than another. There clearly appears to be a strongly positive class effect. Without equivocation, all of these balloons work. Factors such as balloon length, size matrix, and profile are different among the three balloons, which might influence the operator s decision for one DCB over another, but they are all effective. Level 1 Evidence At this point, we clearly have level 1 evidence that all three DCB options provide better outcomes than standard percutaneous transluminal angioplasty (PTA) balloons (Figure 2). 1-6 Nothing, in my opinion, has been studied more extensively in the last decade than DCBs; in fact, they ve been studied to the tune of hundreds of millions of dollars. If we look at the In.Pact, Stellarex, and Lutonix data from all of these studies, we see a clear dramatic improvement in terms of patency. For example, the IN.PACT SFA trial data on primary patency through 2 years 7 are highly statistically significant and show better results in the DCB group versus the PTA group. IN.PACT SFA trial data on 2-year freedom from target-lesion revascularization (TLR) also show better results for DCB versus PTA, and these data are equally impressive when stratified by diabetic status and gender. The Lutonix Global SFA Registry 8 shows a 90.3% freedom from TLR rate at 2 years in a real-world population. ILLUME- NATE EU RCT, 9 a more recent trial that studied the Stellarex DCB, showed 89% primary patency at 12 months versus 65% for PTA. DCBs Work: Freedom From TLR Multiple studies have provided level 1 evidence that DCBs are preferable to PTA balloons (Figure 3) and have shown that DCBs represent a cost-effective therapy. As a result, the Society for Cardiovascular Angiography and Interventions (SCAI) created the first device-focused consensus document for femoral-popliteal interventions. 10 The purpose of the document was to promote data-driven decision-making and understand the relative risk and benefits of DCBs. The SCAI document reviewed comparative effectiveness data, safety, and recommendations for device selection, and found that DCBs were highly effective and that the benefits outweigh the risk and costs. Figure 2. Level 1 evidence: DCB pivotal randomized controlled trials (RCTs) in context. The ILLUMENATE EU RCT was the first trial to show the highest rates of primary patency versus DCB pivotal RCTs of similar design and patient profiles. 1-6 Figure 3. Two-year freedom from target-lesion revascularization at 24 months (90.3% for Lutonix 035 and 83.3% for In.Pact DCBs) demonstrates the superiority of DCBs over percutaneous balloon angioplasty. In fact, multiple cost analysis studies have shown that DCBs are not only effective, they are cost-effective. DCB Reimbursement: A Quick History (Figure 4) The Lutonix balloon was the first DCB in America, and was launched in late In 2015, CMS presented a transitional pass-thru payment; they paid the incremental costs of the DCBs. By the end of 2017, CMS made a decision to include the additional cost of the DCB procedure in the Ambulatory Payment Classification (APC) codes. DCB usage from 2014 to 2017 was used to influence 2018 price increases (Figure 5). Each APC that included DCBs increased. Reimbursement increases were applied to all current procedural terminology (CPT) codes in the APCs where DCBs were historically included. Cost-Effectiveness of DCBs The best intentions aren t always what will yield the best results. If we simply lump DCB costs into payments, and the operator/hospital is paid the same whether they use a DCB or a standard balloon, it won t take hospitals long, in my opinion, to realize they aren t making as much when DCBs are utilized versus when a cheaper standard balloon is used. So, let s examine the word cost-effectiveness. The first word cost is easy. How much does it cost to do something? The real cost should include the overall cost over time, but statisticians very rarely factor this in. The second word effective refers to how well something works. If we examine the early cost-effectiveness studies on DCBs, we see that costs were $1,129 higher in patients treated with a DCB; however, these costs were equal at 2 years ($11,277 vs $11,359). Hospital Profit Margins Are Poor The recent CMS decision will result in better margins if plain old balloon angioplasty (POBA) is used instead of DCB. I suspect this is going to lead to a decrease in DCB use. We have not seen any data or evidence of this in the United States yet, which may be a function of hospitals taking a long time to realize what s happening. In other markets around the world where there was no additional compensation for DCB usage, the usage has fallen. What About Risk? When we look at cost-effectiveness, we must go one step further. Every time we put a patient on a table, there s a real problem in terms of risk and fear. Every procedure carries a risk of bleeding, embolization, contrast allergy, renal dysfunction, etc. Every procedure has associated pain and every procedure is inconvenient; we give these things no monetary value, but our patients have to leave work to undergo these procedures. In addition, every procedure has associated fear; the patient and their family are concerned about the patient s well-being. CMS Decision on No Incremental Payment In conclusion, I believe the CMS s decision was profoundly short-sighted. I believe it will result in less DCB use and therefore worse outcomes. This will happen because 28 Supplement to Cath Lab Digest November 2018 Supplement to Cath Lab Digest November

16 Figure 4. A history of DCB reimbursement since the first DCB (Lutonix) was launched in the United States. 3. Jaff MR. IN.PACT global full clinical cohort. Presented at: VIVA 2016; Las Vegas, Nevada; September 19, [Updated data from IN.PACT SFA presented on slide 12]. 4. Rosenfield K, Jaff MR, White CJ, et al; LEVANT 2 Investigators. Trial of a paclitaxel-coated balloon for femoropopliteal artery disease. N Engl J Med. 2015;373: Brodmann M. First Randomized Trial of the Stellarex Drug-Coated Balloon. Presented at: The Amputation Prevention Symposium; Chicago, Illinois; August 10, Lyden S. ILLUMENATE Pivotal Stellarex DCB IDE Study: 12 month results. Presented at: TCT 2016; Washington, DC; November 2, Schneider PA. IN.PACT SFA TRIAL: Primary Patency Through 2 Years. Presented at Leipzig International Course (LINC) 2016; Leipzig, Germany; January 26-29, Thieme M 1, Von Bilderling P 2, Paetzel C 3, et al; Lutonix Global SFA Registry Investigators. The 24-month results of the Lutonix Global SFA Registry: Worldwide experience with Lutonix drug-coated balloon. JACC Cardiovasc Interv. 2017;10: Schroeder H, Werner M, Meyer DR, et al; ILLUMENATE EU RCT Investigators. low-dose paclitaxel-coated versus uncoated percutaneous transluminal balloon angioplasty for femoropopliteal peripheral artery disease: one-year results of the illumenate european randomized clinical trial (randomized trial of a novel paclitaxel-coated percutaneous angioplasty balloon). Circulation. 2017;135: Feldman DN, Armstrong EJ, Aronow HD, et al. SCAI consensus guidelines for device selection in femoral-popliteal arterial interventions. Catheter Cardiovasc Interv [Epub ahead of print]. Figure 5. DCB reimbursement increases from 2017 to Data presented are the Medicare national average reimbursements for these procedures. Fem/Pop = femoropopliteal; PTA = percutaneous transluminal angioplasty. hospitals will make more per standard PTA procedure, and hospitals will have more procedures after PTA balloons are used because there will be more cases of restenosis. Unfortunately, we are not currently good at measuring overall costs; we are good at measuring a procedure at time zero in a lab. There are further implications that cannot be ignored; eg, the CMS decision may have an impact on the development of new technology. DCBs have been studied extensively at costs that may have exceeded a billion dollars, and have been proven effective beyond any reasonable doubt. And now, there is no compensation for them. The CMS decision may therefore affect whether companies will risk major capital on new projects. References 1. Tepe G, Laird J, Schneider P, et al; IN.PACT SFA Trial Investigators. Drug-coated balloon versus standard percutaneous transluminal angioplasty for the treatment of superficial femoral and popliteal peripheral artery disease: 12-month results from the IN.PACT SFA randomized trial. Circulation. 2015;131: Tepe G. IN.PACT SFA 1-year primary outcomes. Presented at: Charing Cross; London, UK; April 5 8, august 14 17, 2019 hilton chicago chicago, illinois 30 Supplement to Cath Lab Digest November 2018 Supplement to Cath Lab Digest November

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