Clinical Implications of Diabetic Peripheral Neuropathy in Primary Infrapopliteal Angioplasty Approach for Neuro-Ischemic Foot Wounds.

BACKGROUND: To assess the clinical effects of diabetic peripheral neuropathy (DPN) in patients with chronic limb-threatening ischemia (CLTI) treated by primary infrapopliteal angioplasty for neuro-ischemic Rutherford 5, foot wounds. MATERIALS AND METHODS: Over a 10-year period (2009-2019), a series of 304 diabetic ischemic limbs adding or not evincible neuropathic affectation were treated by primary infrapopliteal angioplasty and their files were retrospectively reviewed. Mean length of treated arterial lesions was 6.1 cm (range 1-22 cm). Inferior limb vibration perception threshold diagnostic was performed for comparing and scoring detectable DPN in all studied diabetic patients (classed from 0 to 10 points). There were 19% limbs with normal (0-1 points) perception (group 1), 55% others with "mild" and "moderate" (2-6 points) neuropathic impairment (group 2), and 26% limbs showing "severe" (7-10 points) DPN (group 3). RESULTS: Primary infrapopliteal angioplasty succeeded in 89% cases in group 1, in 82% in group 2, and in 68% of limbs in group 3. This latest group assembled the heaviest neuropathic affectation and arterial calcifications and proved the lowest clinical benefit at 36 months: 35% (95% confidence interval [CI]=22% to 48%) of primary patency, 36% (95% CI=22% to 50%) wound healing, and 54% (95% CI=39% to 69%) limb preservation rates. A comparison between groups 1 vs 3 and 2 vs 3 of primary patency (p=0.014 and p=0.043), tissue healing (p=0.049 and p=0.01), and limb salvage (p=0.006 and p=0.023) proved significant, yet without statistical weight for group 1 vs 2 (p>0.05). Overall survival was not significantly affected between groups (p=0.34). CONCLUSION: The presence of severe DPN may jeopardize the results of infrapopliteal angioplasty in terms of patency, tissue cicatrization, and limb preservation, yet without significance on survival of these patients. When present, DPN requires appropriate stratification as specific indicator in CLTI treatment.

Grades of Below-the-Ankle Arterial Occlusive Disease following the Angiosome Perfusion: A New Morphological Assessment and Correlations with the Inframalleolar GVG Stratification in CLTI Patients.

PURPOSE: To assess a specific classification of the foot atherosclerotic disease concerning the angiosomal source arteries, the connected foot arches and attached collaterals for Rutherford 5, CLTI patients. To compare eventual analogies of this novel grading system with previously reported GLASS/GVG inframalleolar patterns of occlusive disease (P0-P2). MATERIALS AND METHODS: A series of 336 ischemic feet (221 diabetics) were selected and retrospectively analyzed. For each angiographic pattern of inframalleolar atherosclerotic disease, 4 severity classes of targeted angiosomal artery path (TAAP), associating 4 other classes concerning linked foot arches (LFA) and collaterals occlusive disease were described. By associating the 4 TAAP with the 4 others parallel LFA and collaterals classes, 4 novel anatomical "Grades" (A-D) of occlusive disease were described. Limb salvage was studied between groups of diabetic and non-diabetic patients. RESULTS: Using a primary endovascular approach, limb preservation comparison of grade A/B proved without significance for diabetics (P = 0.032) and non-diabetics (P = 0.226). Comparison in diabetics and/or non-diabetics between A/C (P = 0.045 and 0.046), A/D (P = 0.027 and 0.030,B/C (P = 0.009 and 0.038), and B/D (P = 0.006 and P = 0.042), as well as C/D groups (P = 0.048 and P = 0.034) proved ponderous. Parallel analysis of similar grades (A/A, B/B, etc.) with, or without diabetes appeared without significance (P > 0.05). Further comparison between grades A+B (assigned as P0/GVG), versus C (P1), and D (P2), proved significant (P < 0.0001). CONCLUSION: The present grading system proposes a useful correlation between the severity of foot angiosomal arteries, arches, and collaterals disease and limb salvage, confirming the clinical significance of P0-P2 GVG severity score. This analysis also points the limits of EVT to be probably avoided in grade D patients.

Healing of Diabetic Neuroischemic Foot Wounds With vs Without Wound-Targeted Revascularization: Preliminary Observations From an 8-Year Prospective Dual-Center Registry.

Purpose: To assess the clinical efficacy of endovascular angiosome-oriented wound-targeted revascularization (WTR) vs indirect (wound-indifferent) revascularization (IR) in diabetic patients with neuroischemic foot ulcers. Materials and Methods: Between April 2009 and July 2017, 167 diabetic patients (mean age 72.8 years; 137 men) with chronic limb-threatening ischemia (Rutherford category 5) and foot wounds (Wagner 2-4) in 194 limbs were prospectively registered and scheduled for primary infragenicular endovascular treatment. Specific angiosome source artery reperfusion sustained by patent foot arches or arterial-arterial connections was attempted initially. If this approach failed, topographic revascularization via available collaterals (WTRc) and IR were sequentially attempted. Results: Reperfusion was successful in 176 (91%) of 194 limbs (113 with WTR, 28 with WTRc, and 35 with IR); the global angiosome-oriented technical success (WTR and WTRc) was 73% (141/194). The mean follow-up was 10.9±0.7 months (range 3-12.5). Over 1 year, 102 (58%) of the 176 successfully treated limbs experienced wound healing [79/113 (70%) in the WTR group, 15/28 (54%) in the WTRc group, and 7/35 (20%) in the IR group; p=0.011]. The mean time to healing was 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). Relapses were noted in 18 (16%) WTR limbs, 5 (18%) WTRc limbs, and 6 (17%) IR limbs. Comparison between WTR and IR and WTRc vs IR showed improved cicatrization in the angiosome-oriented groups (p<0.05). Major adverse limb events (MALE) and limb salvage were different between WTR and WTRc and between WTR and IR groups (p<0.05), while WTRc vs IR was not. Amputation-free survival was not influenced by the revascularization strategy (p=0.093). Conclusion: Wound healing in diabetic patients with chronic limb-threatening ischemia appeared to be improved by intentional wound-targeted revascularization, but no uniform benefit concerning MALE or limb preservation was observed. IR still represents an alternative for limb salvage in cases in which angiosome-guided revascularization fails.

Global Vascular Guidelines on the Management of Chronic Limb-Threatening Ischemia.

GUIDELINE SUMMARY: Chronic limb-threatening ischemia (CLTI) is associated with mortality, amputation, and impaired quality of life. These Global Vascular Guidelines (GVG) are focused on definition, evaluation, and management of CLTI with the goals of improving evidence-based care and highlighting critical research needs. The term CLTI is preferred over critical limb ischemia, as the latter implies threshold values of impaired perfusion rather than a continuum. CLTI is a clinical syndrome defined by the presence of peripheral artery disease (PAD) in combination with rest pain, gangrene, or a lower limb ulceration >2 weeks duration. Venous, traumatic, embolic, and nonatherosclerotic etiologies are excluded. All patients with suspected CLTI should be referred urgently to a vascular specialist. Accurately staging the severity of limb threat is fundamental, and the Society for Vascular Surgery Threatened Limb Classification system, based on grading of Wounds, Ischemia, and foot Infection (WIfI) is endorsed. Objective hemodynamic testing, including toe pressures as the preferred measure, is required to assess CLTI. Evidence-based revascularization (EBR) hinges on three independent axes: Patient risk, Limb severity, and ANatomic complexity (PLAN). Average-risk and high-risk patients are defined by estimated procedural and 2-year all-cause mortality. The GVG proposes a new Global Anatomic Staging System (GLASS), which involves defining a preferred target artery path (TAP) and then estimating limb-based patency (LBP), resulting in three stages of complexity for intervention. The optimal revascularization strategy is also influenced by the availability of autogenous vein for open bypass surgery. Recommendations for EBR are based on best available data, pending level 1 evidence from ongoing trials. Vein bypass may be preferred for average-risk patients with advanced limb threat and high complexity disease, while those with less complex anatomy, intermediate severity limb threat, or high patient risk may be favored for endovascular intervention. All patients with CLTI should be afforded best medical therapy including the use of antithrombotic, lipid-lowering, antihypertensive, and glycemic control agents, as well as counseling on smoking cessation, diet, exercise, and preventive foot care. Following EBR, long-term limb surveillance is advised. The effectiveness of nonrevascularization therapies (eg, spinal stimulation, pneumatic compression, prostanoids, and hyperbaric oxygen) has not been established. Regenerative medicine approaches (eg, cell, gene therapies) for CLTI should be restricted to rigorously conducted randomizsed clinical trials. The GVG promotes standardization of study designs and end points for clinical trials in CLTI. The importance of multidisciplinary teams and centers of excellence for amputation prevention is stressed as a key health system initiative.

Midterm Outcomes From a Pilot Study of Percutaneous Deep Vein Arterialization for the Treatment of No-Option Critical Limb Ischemia.

PURPOSE: To report the initial clinical experience with percutaneous deep vein arterialization (PDVA) to treat critical limb ischemia (CLI) via the creation of an arteriovenous fistula. METHODS: Seven patients (median age 85 years; 5 women) with CLI and no traditional endovascular or surgical revascularization options (no-option CLI) were recruited in a pilot study to determine the safety of PDVA. All patients were diabetic; 4 had Rutherford category 6 ischemia. Six were classified at high risk of amputation based on the Society for Vascular Surgery WIfI (wound, ischemia, and foot infection) classification. The primary safety endpoints were major adverse limb events and major adverse coronary events through 30 days and serious adverse events through 6 months. Secondary objectives included clinical efficacy based on outcome measures including thermal measurement, transcutaneous partial pressure of oxygen (TcPO2), clinical improvement at 6 months, and wound healing. RESULTS: The primary safety endpoints were achieved in 100% of patients, with no deaths, above-the-ankle amputations, or major reinterventions at 30 days. The technical success rate was 100%. Two myocardial infarctions occurred within 30 days, each with minor clinical consequences. All patients demonstrated symptomatic improvement with formation of granulation tissue, resolution of rest pain, or both. Complete wound healing was achieved in 4 of 7 patients and 5 of 7 patients at 6 and 12 months, respectively, with a median healing time of 4.6 months (95% confidence interval 84-192). Median postprocedure peak TcPO2 was 61 mm Hg compared to a preprocedure level of 8 mm Hg (p=0.046). At the time of wound healing, 4 of 5 of patients achieved TcPO2 levels of >40 mm Hg. There were 2 major amputations, 1 above the knee after PDVA thrombosis and 1 below the knee for infection. Three patients died of causes unrelated to the procedure or study device at 6, 7, and 8 months, respectively. Limb salvage was 71% at 12 months. CONCLUSION: PDVA is an innovative approach for treating no-option CLI and represents an alternative option for the "desert foot," potentially avoiding major amputation. Our results demonstrate its safety and feasibility, with promising early clinical results in this small cohort.

Angiosome-Targeted Infrapopliteal Angioplasty: Impact on Clinical Outcomes-An Observational Study.

Background: Revascularization based on the angiosome concept (AC) is a controversial subject because there is currently no clear evidence of its efficacy, due to the heterogeneity of patients (multiple and diverse risk factors and comorbidities, multiple variations in the affected angiosomes). Choke vessels change the paradigm of the AC, and the presence or absence of the plantar arch directly affects the course of targeted revascularization. The aim of this study was to evaluate the effect of revascularization based on the AC in diabetic patients with chronic limb-threatening ischemia (CLTI). Methods: This retrospective analysis included 51 patients (40 men, 11 women), with a mean age of 69 years (66-72) and a total of 51 limbs, who presented with Rutherford 5-6 CLTI, before and after having undergone a drug-coated balloon angioplasty (8 patients) or plain balloon angioplasty (43). Between November 2018 and November 2019, all patients underwent below-the-knee balloon angioplasties and were followed up for an average of 12 months. The alteration of microcirculation was compared between directly and indirectly revascularized angiosomes. The study assessed clinical findings and patient outcomes, with follow-up investigations, comparing wound healing rates between the different revascularization methods. Patient records and periprocedural leg digital subtraction angiographies (DSA) were analyzed. Differences in outcomes after direct revascularization and indirect percutaneous transluminal angioplasty (PTa) were examined using Cox proportional hazards analysis, with the following endpoints: ulcer healing, limb salvage, and also amputation-free survival. Results: Direct blood flow to the angiosome supplying the ulcer area was achieved in 38 legs, in contrast to 13 legs with indirect revascularization. Among the cases, there were 39 lesions in the anterior tibial artery (ATA), 42 lesions in the posterior tibial artery (PTA), and 8 lesions in the peroneal artery (PA). According to a Cox proportional hazards analysis, having fewer than three (<3) affected angiosomes (HR 0.49, 95% CI 0.19-1.25, p = 0.136) was associated with improved wound healing. Conversely, wound healing outcomes were least favorable after indirect angioplasty (p = 0.206). When adjusting the Cox proportional hazard analysis for the number of affected angiosomes, it was found that direct drug-coated angioplasty resulted in the most favorable wound healing (p = 0.091). At the 1-year follow-up, the major amputation rate was 17.7%, and, according to a Cox proportional hazards analysis, atrial fibrillation (HR 0.85, 95% CI 0.42-1.69, p = 0.637), hemodialysis (HR 1.26, 95% CI 0.39-4.04, p = 0.699), and number of affected angiosomes > 3 (HR 0.94, 95% CI 0.63-1.39, p = 0.748) were significantly associated with poor leg salvage. Additionally, direct endovascular revascularization was associated with a lower rate of major amputation compared to indirect angioplasty (HR 1.09, 95% CI 0.34-3.50, p = 0.884). Conclusions: Observing the angiosomes concept in decision-making appears to result in improved rates of arterial ulcer healing and leg salvage, particularly in targeted drug-coated balloon angioplasty for diabetic critical limb ischemia, where multiple angiosomes are typically affected.

Selective primary angioplasty following an angiosome model of reperfusion in the treatment of Wagner 1-4 diabetic foot lesions: practice in a multidisciplinary diabetic limb service.

PURPOSE: To evaluate the technical and clinical outcomes of primary subintimal (SA) and endoluminal angioplasty (EA) guided by an angiosome model of revascularization in diabetic patients with critical limb ischemia (CLI) and Wagner grade 1-4 foot ulcers. METHODS: A retrospective review was undertaken of 98 diabetic CLI patients (68 men; mean age 72.8 years, range 46-94) who presented to our institution from January 2005 to January 2008 for treatment of Wagner grade 1-4 foot ulcers involving 124 limbs. Following the angiosome model of perfusion in the foot and ankle, the target arterial lesions in the 124 limbs were treated with 80 (64%) associated SA and EA procedures, 21 (17%) multilevel EAs, and 23 (18%) single SA techniques. RESULTS: Initial technical success was achieved in 102 (82%) interventions: 82/103 SAs and 20/21 of the EAs. The 30-day survival rate was 98% (1 fatal myocardial infarction). The cumulative rates of primary and secondary patency, limb salvage, and clinical success were: 57%+/-4%, 71%+/-4%, 91%+/-3%, and 85%+/-3% at 12 months and 48%+/-5%, 61%+/-4%, 84%+/-6%, and 73%+/-6% at 32 months, respectively. Limb salvage appeared to be negatively affected at 3 years by the presence of Wagner grade 3-4 lesions (p<0.0002), the bedridden condition of patients (p<0.0001), end-stage renal disease (p<0.0001), left ventricular dysfunction (p<0.0001), and peripheral neuropathy (p = 0.023). Using the angiosome approach, complete healing of ulcers with or without minor amputation was seen in 79% (98/124 limbs), while 62 of 70 Wagner grade 1-2 and 36 of 54 Wagner 3-4 foot lesions healed in the first 1 to 3 months after revascularization. CONCLUSION: Targeted primary angioplasty following the angiosome model could be an effective therapeutic method in the ulcer healing process. However, beyond appropriate revascularization, aggressive control of concurrent risk factors in diabetic wound healing probably plays an equally relevant role.