A primer on what every IR needs to know
By Omosalewa Adenikinju, MD, Robert E. Beasley, MD, Timothy Yates, MD, and Brandon Olivieri, MD Winter 2019
Ischemic rest pain and tissue loss from atherosclerosis, or critical limb ischemia (CLI), represents the end stage of peripheral arterial disease (PAD). Vascular specialists are trained to recanalize arterial stenoses and occlusions with a high degree of precision. However, managing this systemic disease requires multidisciplinary effort to aid early detection and stratify treatment. In this article, we offer the interventionalist a primer approach on cutting-edge wound care, all of which will take place outside of the angiography suite.
In a normal response to tissue injury, the body’s wound-healing cascade is initiated. The progression begins with an inflammatory phase, which prompts cytokines to invoke a complex cellular response leading to phagocytosis, angiogenesis and granulation tissue.2,3 This is augmented in the proliferative phase as neo-angiogenesis allows delivery of nutrients to the wound and promotes fibroplasia and collagen tensile strength. These steps ultimately lead to complete restoration in the remodeling phase.2
However, this progression is abnormal in the CLI patient. The chronically hypoxic environment promotes prolonged inflammation from oxidative stress, nutrient deprivation, and cytokine and growth factor imbalance. Additionally, there tends to be an excess of proteolytic enzymes such as matrix metalloproteinases, which ultimately perpetuate the nonhealing wound.4,5
Although arterial insufficiency is implicated as a contributing component in many nonhealing lower extremity ulcers, it is important to recognize that advanced venous disease also prevents adequate oxygen and micronutrient delivery to and from the wound bed.4 Given that many CLI patients have a history of smoking and obesity, they can have mixed arterial and venous pathology. These confounders can augment patient findings, further complicating the picture for the clinician.
Patient symptoms and physical examination can be help differentiate between the two etiologies. Typically, venous wounds are exudative and painless (in the absence of infection), often with surrounding varicosities and edema in the gaiter zones (medial and lateral malleoli). They are usually the sequelae of chronic venous hypertension.6,7
Arterial ulcers, in contrast, arterial ulcers are usually painful and necrotic, affecting the acral appendages (digits), often in the clinical setting of neuropathic, accidental or repeated injury. Employing the “angiosome” concept and other perfusion modalities (e.g., methylene blue, FluoBeam®, HyperViewTM), we are able to predict where we can expect to find disease on noninvasive and angiographic studies.
Initial radiographs and cross-sectional imaging (CT/MR) are often obtained to evaluate for osteomyelitis, a common cause for chronic nonhealing wounds that portends a worse prognosis. Infection is a factor that increases risk for amputation, according to the Society for Vascular Surgery lower extremity threatened limb/WIfI classification system8, thus it must be recognized and corrected promptly.
After considering the “typical players,” vascular specialists need to consider other potential causes for treatment failure. One such factor is patient insight. Critical limb ischemia patients need to be enlightened and empowered about the genesis of their wounds and given tools to prevent progression. In fact, the literature has shown that patient insight is critical to combat this disease.9 Typically built on years of unhealthy lifestyle habits, it takes a great deal of effort to make the lifestyle changes necessary to optimize the wound healing environment.
Lifestyle modifications can be prioritized as follows:
- Most important lifestyle
- Lower patency rates after revascularization and even higher amputation rates in smokers
- Recommendation: Cessation
- Equip patients to change and set objectives to foster desire for an improved quality of life
- Offer resources for behavior change (pamphlets, support groups)
- Medication (e.g., nicotine supplements)
- Elevated glycosylated hemoglobin levels (HgA1c) are associated with poor wound healing, higher amputation rates11
- Aggressive HgA1c monitoring
- Endocrinological consultation
- Low-sugar diet
Medical management of concurrent lipid and hypertension management based on the ACC-AHA guidelines (a class 1a recommendation in CLI patients) is also crucial to promoting healing.12 Medical optimization is crucial in creating the optimal wound healing environment. However, in-depth review of the complete medical management of CLI is beyond the scope of this article.
Once proper medical management has been initiated and the patient condition is deemed amenable to intervention, we proceed with a diagnostic angiogram and intervention with the goal of restoring angiographosomal or wound-related artery-directed13,14 blood flow to the wound, with specific techniques being beyond the scope of this article. Our surgical colleagues may use blood at the site of surgical wound debridement as a marker for interventional success. Traditional benchmarks for successful reperfusion after lower extremity arterial revascularization include angiographic luminal gain, contrast washout and wound blush.15 However, we have seen discordant results at the microvascular level with wound healing failure despite advances in “technically successful” below-the-knee, ankle and even pedal loop reconstructions.
Several emerging technologies can be useful in assessing distal perfusion, facilitating the decision on whether to proceed with debridement, amputation or further revascularization. One such technology is near-infrared fluorescence angiography (NIFA), which uses indocyanine green (ICG) dye to assess a semiquantitative measurement of dermal and subdermal microcirculation.16 (See following case.) In addition to immediate postrevascularization optical feedback, early research has demonstrated the accuracy of quantitative ICG analysis after intervention when compared to standard perfusion measures, such as ankle brachial indices (ABIs).17 This is especially helpful when ABI accuracy is limited by noncompressible, calcified, diseased vessels, present in many of our patients with poorly controlled diabetes and end-stage renal disease.
Another perfusion assessment that has proved useful in analyzing PAD is hyperspectral tissue oxygenation measurement (HTOM), as seen in the handheld HyperViewTM device. It measures oxygen saturation, oxyhemoglobin and deoxyhemoglobin levels of the superficial subcutaneous tissue, creating color-coded anatomic images based on tissue oxygenation, providing a measure of perfusion. Implementing perfusion analysis in our multidisciplinary practice has helped us optimize patient outcomes by determining periwound perfusion as a surrogate for tissue viability.
Case illustration and conclusion
70-year-old female with history of hyperlipidemia, hypertension, 60 pack-year former smoker, with PAD/CLI referred for evaluation of worsening severe bilateral ulcerations on the feet for several months. Physical exam demonstrated severe gangrene of the 2nd left toe (Fig. 2) compatible with Rutherford 6 and severe gangrene at the lateral plantar aspect of the left 1st digit (Fig. 2) compatible with Rutherford 5 classification. After the patient was optimized for wound healing, we proceeded with angiography with collaboration with the podiatry service with plan for follow-up debridement.
Left lower extremity angiogram demonstrated 80 percent stenosis of the entire left external iliac artery (EIA), flush occlusion of the left SFA with reconstitution at the level of the adductor canal, and focal left P2 popliteal artery occlusion with two-vessel infrapopliteal runoff via the left posterior tibial and peroneal arteries. Staged revascularization was successful with angioplasty and self-expanding stent placement resolving the left external iliac artery stenosis (Fig. 1).
Following this, an antegrade-retrograde approach was used to recanalize the left anterior tibial artery, P2 popliteal artery occlusion and flush SFA occlusion, with orbital atherectomy, angioplasty/drug-coated balloon angioplasty and drug-eluting stent placement (Fig. 1). Final angiographic images revealed rapid blood flow to the foot with filling of the deep pedal arch, but with persistent nonfilling of the pedal-plantar loop due to chronic occlusion of the left dorsalis pedis and left lateral plantar arteries (Fig. 1). Given the extent of revascularization performed, decision was made to send the patient for NIFA analysis to determine the adequacy of postrevascularization pedal perfusion prior to any more aggressive pedal-plantar loop revascularization.
Subsequent selective surgical debridement was then performed using NIFA to assess for adequate perfusion post-debridement. Left 1st hallux debridement was performed with removal of all nonviable soft tissue per NIFA (Fig. 2). The gangrenous 2nd toe was then evaluated with NIFA revealing no perfusion (Fig. 2), and therefore 2nd toe amputation was performed. NIFA also revealed nonviability of the adjacent 3rd toe; however, amputation was not performed due to lack of rest pain or gangrenous changes (Fig. 2). The patient was then discharged home with close follow-up in our multidisciplinary wound care clinic.
As demonstrated in this case, new noninvasive methods of tissue perfusion assessment demonstrate promise in the future of revascularization and wound care.
With a foundational knowledge in wound pathophysiology and of the multifactorial approach needed to fight this systemic disease, coupled with evolving endovascular techniques and perfusion analyses highlighted in this article, the interventionalist can be equipped to restore meaningful perfusion to aid limb preservation.
Read a companion article on practice management of wound care.
- Boguszewski, Andrzej, et al. “Endovascular Today—Intraluminal Recanalization of SFA CTOs.” Endovascular Today, Retrieved from evtoday.com/2010/05/intraluminal-recanalization-of-sfa-ctos/.
- Gonzalez, A. C., Costa, T. F., Andrade, Z. D., & Medrado, A. R. (2016). Wound healing—A literature review. Anais Brasileiros de Dermatologia, 91(5), 614–620. doi:10.1590/abd1806-4841.20164741.
- Mendonça RJ, Coutinho-Netto J. Aspectos celulares da cicatrização. An Bras Dermatol 2009;84:257–262.
- Stadelmann WK, Digenis AG, Tobin GR. Physiology and healing dynamics of chronic cutaneous wounds. Am J Surg. 1998;176(2A Suppl):26S–38S.
- Medina A, Scott PG, Ghahary A, Tredget EE. Pathophysiology of chronic nonhealing wounds. J Burn Care Rehabil. 2005;26(4):306–319.
- Almeida, O. I., & Boatright, C. (2012, May). Endovascular Today—Venous Issues Relative to CLI. Retrieved from https://evtoday.com/2012/05/venous-issues-relative-to-cli/.
- Grey, J. E., Harding, K. G., & Enoch, S. (2006). Venous and arterial leg ulcers. BMJ, 332(7537), 347–350. doi:10.1136/bmj.332.7537.347
- Mills, J. L., Conte, M. S., Armstrong, D. G., Pomposelli, F. B., Schanzer, A., Sidawy, A. N., & Andros, G. (2014). The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: Risk stratification based on Wound, Ischemia, and foot Infection (WIfI). Journal of Vascular Surgery, 59(1), 220–234.e2. doi:10.1016/j.jvs.2013.08.003.
- Eurobarometer Qualitative Study on patient involvement in healthcare—EUROPEAN INNOVATION PARTNERSHIP—European Commission. EUROPEAN INNOVATION PARTNERSHIP. https://ec.europa.eu/eip/ageing/library/eurobarometer-qualitative-study-patient-involvement-healthcare_en. Published May 21, 2012. Accessed August 18, 2018.
- Jonason T, Bergström R. Cessation of smoking in patients with intermittent claudication. Effects on the risk of peripheral vascular complications, myocardial infarction and mortality. Acta Med Scand. 1987;221(3):253–260.
- Watts, S. A., Daly, B., Anthony, M., McDonald, P., Khoury, A., & Dahar, W. (2005). The Effect of Age, Gender, Risk Level and Glycosylated Hemoglobin in Predicting Foot Amputation in HMO Patients with Diabetes. Journal of the American Academy of Nurse Practitioners, 13(5), 230–236. doi:10.1111/j.1745-7599.2001.tb00026.
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- Neville RF, Attinger CE, Bulan EJ, Ducic I, Thomassen M, Sidawy AN. Revascularization of a specific angiosome for limb salvage: does the target artery matter? Ann Vasc Surg. 2009;23:367–373.
- Utsunomiya M, Nakamura M, Nakanishi M, Takagi T, Hara H, Onishi K, et al. Impact of wound blush as an angiographic end point of endovascular therapy for patients with critical limb ischemia. J Vasc Surg. 2012;55:113–121.
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