Angiosome theory guide to revascularization for CLI Richard

Angiosome theory: guide to revascularization for CLI Richard F. Neville, MD, FACS Associate Director, INOVA Heart and Vascular Institute Vice-Chairman, IFMC Department of Surgery System Director, INOVA Vascular Services Clinical Professor of Surgery, George Washington U

Disclosures • Nothing related to disclose

CLI and wound healing • Despite successful revascularization, 15 -25% of wounds fail to heal, often leading to amputation • Factors • Method of wound care • Medical optimization • Persistent inadequate perfusion • Microvascular disease • Pedal arch • Angiosome based revascularization

Angiosome concept • • Angiosome: Anatomic unit of tissue (skin, muscle, bone, nerve) fed by a single source artery 40 defined in the body

Angiosomes of the lower leg and foot Six distinct angiosomes: • Anterior tibial artery (1) • Dorsalis pedis • Peroneal artery (2) • Lateral calcaneal • Anterior perforator • Posterior tibial artery (3) • Calcaneal • Medical plantar • Lateral plantar Attinger CE, et al. Plastic and Reconstr Surg 2006: 117; 261 S-293 S Cadaveric dissection with colored latex injections

Angiosome anatomy: Anterior Tibial Dorsalis pedis Anterior compartment Dorsum of foot

Angiosome anatomy: Peroneal Lateral calcaneal artery Anterior perforator Medial ankle Lateral plantar heel

Angiosome anatomy: Posterior Tibial Medial plantar artery Lateral plantar artery Calcaneal perforator Lateral ankle/forefoot

Clinical correlation Direct vs Indirect revascularization • 60 consecutive ischemic wounds • Tibial bypasses • Direct Revascularization (DR) Bypass to the artery perfusing the wound’s angiosome • Indirect Revascularization (IR) Bypass to an artery Neville RF, et al. Ann Vasc Surg 2009; 23: 367 -373. not directly perfusingthe wound’s angiosome

Wound healing Standard wound care protocol No difference in wound care between groups DR IR Primary closure / STSG 35% 24% Local amputation Ray/TMA/Chopart 60% 69% Free flap 5% 7%

Angiosome revascularization Healing more complete with Direct Revascularization of the wound’s angiosome by surgical bypass Direct revascularization Indirect revascularization 91% 62% P = 0. 03 Neville RF, et al. Ann Vasc Surg 2009; 23: 367 -373.

Angiosome revascularization Healing faster with direct revascularization of the wound’s angiosome by surgical bypass

Angiosome theory: does it matter? Indirect connections • Arterial-arterial connection: “Choke vessels” • Pedal arch Wounds not confined to strict borders

Angiosome concept; does it matter Endovascular • Healing of diabetic ischemic ulcers after endovascular revascularization DR 83% healed IR 59% healed “An angiosome model of perfusion, helps the treatment of diabetic foot ulcers” Alexandrescu, et al. J Endovasc Therapy 2008; 15: 580

Angiosome concept; does it matter Endovascular • 203 ischemic ulcers • Procedures – Iliac PTA – SFA stenting – Tibial PTA 17% 54% 82% • Healing improved with DR – Direct R – Indirect R Iida, et al. Endo Today 2010; September: 96 -100. 86% 69%

Angiosome concept; does it matter Endovascular • Ischemic diabetic foot ulcers (n=250) • Improved healing (12 m) with DR – Direct R 72% – Indirect R 45% “Important for ulcer healing in diabetic patients” Soderstrom M, et al. J Vasc Surg 2013; 57: 427 -35. DR IR

Angiosome concept: does it matter Surgical bypass • Oregon Health Sciences University • n=106 bypasses • More complete healing in the DR group(p=. 001) – DR 78% vs IR 46% • More rapid time to healing in the DR group(p=. 002) – DR 99 days vs IR 195 days • Only 36% of wounds in a single angiosome Kret et al. J Vasc Surg 2014; 59: 1: 121 -8.

Angiosome concept: does it matter Surgical bypass • n=58 tibial bypasses for tissue loss – 36 DR – 22 IR • More rapid healing in the DR group – 56 days vs 112 days • Limb salvage higher in DR group – 1 year: – 5 years: Lejay A, et al. Ann Vasc Surgery 2014; 28(4): 983 -9. 91% vs. 66% 58% vs. 18%

Angiosome concept; does it matter Surgical bypass • Universities of Poitiers and Bologna • Peroneal bypass (n=120) • Amputation Free Survival (3 years) – DR vs IR made no difference • What did improve Amputation Free Survival – Patency of both peroneal collateral branches – Patency of pedal arch • Only 46% of wounds in a peroneal angiosome Ricco et al. J Vasc Surg 2017; 66: 1479 -87

Angiosome concept; clinical results Direct revasc Indirect revasc Method Neville Lejay Alexandrescu 91 62 Bypass 91 66 Bypass 83 59 Endovascular Iida Kret Kabra Soderstrom 86 69 Endovascular 78 46 Bypass 96 83 Bypass/Endo 72 45 Endovascular Over 700 limbs studied

Angiosome systemic review • 11 studies • 1757 limbs • Findings: Trial Heterogeneity • • • Inclusion criteria Reporting of indications Clinical assessment Measure of perfusion Measure of wounds

Angiosome systemic review • Wound healing and time to healing • DR significant improvement in 5/8 studies • Limb salvage • DR significant improvement in 4/8 studies “More clinical evidence in the form of well-structured, prospective studies must be available before widespread adoption can be advocated. ”

Angiosome meta-analysis • 9 studies • 1290 limbs • 715 DR • 575 IR • Open & Endovascular • Outcomes • Limb salvage • Wound healing

Angiosome meta-analysis Biancari, 2013 DR significantly lowers the risk of an unhealed wound (HR 0. 64, 95% CI: 0. 52 -0. 8, I 2 0%) DR is associated with lower risk of major amputation (HR 0. 44, 95% CI: 0. 26 -0. 75, I 2 62%)

Angiosome meta-analysis • • • 15 studies 1868 limbs Open and Endovascular 6 “high quality” analyses Outcomes: • Wound healing • Re-intervention • Limb preservation • Mortality

Angiosome meta-analysis § Wound healing § Significantly greater rate w/ DR § OR 0. 40, 95% CI 0. 29– 0. 54, p <. 00001, I 2 = 0% § Limb preservation § Significantly improved rate w/ DR § OR 0. 24, 95% CI 0. 13– 0. 45, p <. 0001, I 2 = 73%) § Maintained for endo & open analysis

Do we need a new category? • Direct Revascularization • Indirect with connections (IRc) – Direct (DR) = Indirect with connections (IRc) • No difference in healing and limb preservation – Indirect (IR) vs Indirect with connections (IRc) • IR with significant difference in healing and limb preservation Varela C, et al. Vasc Endovascular Surg. 2010 Nov; 44(8): 654 -60

Angiosome theory: when does it not matter • When does the angiosome conceptnot make a difference? – Wounds not located in a single, distinct angiosome – Specific angiosome related revascularization not possible – Indirect connections present (intact pedal arch)

Angiosome: Societal guidelines

Angiosome theory: does it matter? • Direct Revascularization of the appropriate angiosome does result in increased healing • The angiosome concept should be considered in planning revascularization for healing • May be most important for; – Endovascular therapy – Diabetic revascularization – Wound in a single angiosome • The angiosome concept matters when it can be utilized without sacrifice of other principles of revascularization

Thank you