Commentary: Wound-Directed Revascularization for the Treatment of Diabetic Foot Ulcers: Comments on a Newly Proposed Algorithm

In the February 2020 issue of the JEVT, Alexandrescu et al ¹ report the midterm outcomes of a large, prospective, dual-center registry investigating wound-directed (angiosome-oriented) vs non-wound-directed endovascular revascularization for the treatment of ischemic or mixed neuroischemic diabetic foot ulcers (DFU). The importance of such a study is strongly supported by the continuously increasing incidence of diabetes worldwide and the immense socioeconomic impact of its ischemic complications, which include chronic foot ulcerations and major limb amputations.^1,2 Although endovascular revascularization is a well-established treatment option for DFU, ³ midterm wound healing data are scarcely reported in the literature.^4–6 Wound healing and time to wound healing are extremely important hard clinical endpoints that should be included in all DFU studies, as they are correlated with quality of life and cost-effectiveness outcomes.^7,8 Moreover, over the past years, the angiosome theory has emerged as a wound-orientated revascularization strategy to enhance wound healing and limb salvage, but as of today the level of evidence remains low. ⁹

Despite the limitations of the present study (small number of patients, loss to follow-up, inherent limitations in angiography interpretation, selection bias, etc), Alexandrescu et al ¹ add several new and important, good-quality clinical and technical data to the literature. Firstly, a new treatment algorithm has been prospectively investigated, proposing 3 different infrapopliteal revascularization options: angiosome-oriented wound-targeted revascularization (WTR), topographic revascularization via available medium- to small-caliber collaterals (WTRc), and indirect (wound-indifferent) revascularization (IR). Interestingly, this is the first large prospective series comparing the utilization of medium-to-small collaterals (including the choke vessels) or cutaneous perforators toward the angiosomes of the wound zone (WTRc) with the other two available infrapopliteal revascularization techniques in DFU cases.

According to the authors’ findings, wound-directed revascularization should be the first option, as faster wound healing was noted in patients following angioplasty of the vessel directly supplying blood to the wound [mean time to wound healing 6.8±0.4 months in the WTR group, 7.9±0.6 months in the WTRc group, and 9.8±0.7 months in the IR group (p=0.001)]. Moreover, significantly improved cicatrization, limb salvage, and reduced major adverse limb events following angiosome-directed revascularization were noted in both angiosome-focused groups. Therefore, the use of collateral circulation to achieve direct wound reperfusion (WTRc) should be the second option if WTR is not technically feasible.

These results are in line with previously described outcomes indicating that direct angiosome-based revascularization improves wound perfusion and decreases time to wound healing. ⁹ On the other hand, amputation-free survival in successfully treated patients was not influenced by the revascularization strategy and was around 75% at 1 year for all 3 subgroups, highlighting the high mortality risk present in patients with diabetes and chronic limb-threatening ischemia (CLTI) as well as a possibly diminished effect of angiosome-targeted revascularization in limb preservation. Patency outcomes were also similar in all 3 treatment strategies but numerically superior in both angiosome-directed groups.

Although the specific treatment algorithm suggested by the outcomes of this registry seems effective, there are certain issues that need to be highlighted. Among them are the quality of the pedal arch and the use of pedal arch angioplasty, factors that directly affect foot perfusion and should be included in decision making. Specifically, one could argue that non-angiosome-directed revascularization could result in similar clinical outcomes if the pedal-plantar loop is complete or adequately revascularized to establish a communication between the pedal and lateral plantar arteries. This concept becomes substantial in cases in which IR is not technically challenging (eg, stenosis), but its use in complex wound-directed revascularizations could result in clinical disasters, especially in the hands of less experienced operators.

Additionally, aiming for reperfusion of the main outflow vessel contributing to the formation of a complete pedal-plantar loop could be preferred over direct revascularization with poor pedal arch outflow. On the other hand, different foot areas require different approaches. As the authors correctly outline, heel ulcers are poorly perfused by the anterior tibial circulation, so slow or poor healing is expected with indirect reperfusion. However, as noted by other authors,^10,11 the foot arterial network in subjects with CLTI and diabetes may be altered. Therefore, the standard angiosome model may not be valid, and a different assessment of foot perfusion should be adopted in order to guide revascularization. ¹⁰ This could explain the fact that revascularization of more than one tibial vessel and combined direct and indirect revascularization have also been reported to improve limb salvage outcomes.^9,12,13

In order to clarify such issues, improve treatment algorithms, and enhance clinical outcomes of infrapopliteal revascularization, wound-directed vs non-wound-directed angioplasty, multivessel revascularization, and the contribution of the pedal arch following IR in foot perfusion should be investigated using novel in vivo methods of intraprocedural tissue perfusion monitoring and quantification, such as near-infrared spectroscopy and 2-dimensional perfusion digital subtraction angiography.^13–16

Other issues remaining unanswered are the effect of rapid wound healing on the patient’s quality of life and the preferred treatment strategy for infrapopliteal disease in dialysis patients who were not included in this registry but constitute a large cohort of patients in everyday practice. ¹⁷

Conclusively, Alexandrescu et al ¹ provide elegant midterm data regarding the endovascular treatment of infrapopliteal arterial disease causing DFU and supports the importance of wound-directed revascularization, even via medium-to-small collaterals or cutaneous perforators toward the wound zone. Assessment and improvement of the quality of the pedal arch combined with intraprocedural tissue perfusion monitoring could further optimize the treatment algorithm and enhance clinical outcomes.