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Contemporary quality control methods are often insufficient in predicting clinical outcomes after revascularization in lower extremity arterial disease (LEAD) patients. This study evaluates the potential of near-infrared fluorescence imaging with indocyanine green to predict the clinical outcome following revascularization. Near-infrared fluorescence imaging was performed before and within 5 days following the revascularization procedure. Clinical improvement was defined as substantial improvement of pain free walking distance, reduction of rest- and/or nocturnal pain, or tendency toward wound healing. Time-intensity curves and 8 perfusion parameters were extracted from the dorsum of the treated foot. The quantified postinterventional perfusion improvement was compared within the clinical outcome groups. Successful near-infrared fluorescence imaging was performed in 72 patients (76 limbs, 52.6% claudication, 47.4% chronic limb-threatening ischemia) including 40 endovascular- and 36 surgical/hybrid revascularizations. Clinical improvement was observed in 61 patients. All perfusion parameters showed a significant postinterventional difference in the clinical improvement group ( P -values <.001), while no significant differences were seen in the group without clinical improvement ( P -values .168-.929). Four parameters demonstrated significant differences in percentage improvement comparing the outcome groups ( P -values within .002-.006). Near-infrared fluorescence imaging has promising additional value besides clinical parameters for predicting the clinical outcome of revascularized LEAD patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The diagnosis of peripheral arterial disease (PAD) is commonly applied for symptoms related to atherosclerotic obstructions in the lower extremity, though its clinical manifestations range from an abnormal ankle-brachial index to critical limb ischemia. Subsequently, management and prognosis of PAD vary widely with the disease stage. A critical aspect is how this variation is addressed in administrative database-based studies that rely on diagnosis codes for case identification. The objective of this scoping review is to inventory the identification strategies used in studies on PAD that rely on administrative databases, to map the pros and cons of the International Classification of Diseases (ICD) codes applied, and to propose a first outline for a consensus framework for case identification in administrative databases., Methods: Registry-based reports published between 2010 and 2021 were identified through a systematic PubMed search. Studies were subcategorized on the basis of the expressed study focus: claudication, critical limb ischemia, or general peripheral arterial disease, and the ICD code(s) applied for case identification mapped., Results: Ninety studies were identified, of which 36 (40%) did not specify the grade of PAD studied. Forty-nine (54%) articles specified PAD grade studied. Five (6%) articles specified different PAD subgroups in methods and baseline demographics, but not in further analyses. Mapping of the ICD codes applied for case identification for studies that specified the PAD grade studied indicated a remarkable heterogeneity, overlap, and inconsistency., Conclusions: A large proportion of registry-based studies on PAD fail to define the study focus. In addition, inconsistent strategies are used for PAD case identification in studies that report a focus. These findings challenge study validity and interfere with inter-study comparison. This scoping review provides a first initiative for a consensus framework for standardized case selection in administrative studies on PAD. It is anticipated that more uniform coding will improve study validity and facilitate inter-study comparisons., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Diagnosing peripheral arterial disease (PAD) can be challenging owing to medial arterial calcification (MAC) in patients with diabetes mellitus (DM) and chronic kidney disease (CKD). Current bedside tests, such as the ankle-brachial index and toe-brachial index, are often insufficient. The maximal systolic acceleration (ACC max ) is a velocimetric Doppler-derived parameter and could be a new promising test in the diagnostic workup of these patients. The primary aim of this study was to evaluate the diagnostic performance of the ACC max to detect PAD., Methods: A retrospective cohort study was performed in a tertiary referral hospital. Patients ≥18 years old with suspected PAD who underwent ACC max measurement(s) along with computed tomography angiography of the abdominal aorta and lower extremities (reference test) were eligible for inclusion. ACC max measurements of the posterior tibial artery, anterior tibial artery and peroneal artery were collected. Diagnostic performance was assessed by using sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and area under the curve (AUC)., Results: In total, 340 patients (618 limbs) were included. Approximately 40% suffered from DM and 30% had CKD. Diagnostic performance of the ACC max to detect PAD for the posterior tibial artery showed a sensitivity of 90%, specificity of 93%, positive likelihood ratio of 12.83, and negative likelihood ratio of 0.11 (AUC, 0.953). For the anterior tibial artery, these results were 94%, 97%, 32.06, and 0.06 (same sequence as presented before) with an AUC of 0.984. The peroneal artery had a performance of 86%, 89%, 7.51, and 0.16, respectively (AUC, 0.893). Diagnostic accuracy of the ACC max did not diminish in subgroup analysis for patients with DM or CKD., Conclusions: The ACC max showed excellent diagnostic performance to detect PAD, independent of patients prone to medial arterial calcification., Competing Interests: Disclosures None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Current diagnostic modalities for patients with peripheral artery disease (PAD) mainly focus on the macrovascular level. For assessment of tissue perfusion, near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) seems promising. In this prospective cohort study, ICG NIR fluorescence imaging was performed pre- and post-revascularization to assess changes in foot perfusion., Methods: ICG NIR fluorescence imaging was performed in 36 patients with PAD pre- and post-intervention. After intravenous bolus injection of 0.1 mg/kg ICG, the camera registered the NIR fluorescence intensity over time on the dorsum of the feet for 15 min using the Quest Spectrum Platform®. Time-intensity curves were plotted for three regions of interest (ROI): (1) the dorsum of the foot, (2) the forefoot, and (3) the hallux. Time-intensity curves were normalized for maximum fluorescence intensity. Extracted parameters were the maximum slope, area under the curve (AUC) for the ingress, and the AUC for the egress. The non-treated contralateral leg was used as a control group., Results: Successful revascularization was performed in 32 patients. There was a significant increase for the maximum slope and AUC egress in all three ROIs. The most significant difference was seen for the maximum slope in ROI 3 (3.7%/s to 6.6%/s, p < 0.001). In the control group, no significant differences were seen for the maximum slope and AUC egress in all ROIs., Conclusions: This study shows the potential of ICG NIR fluorescence imaging in assessing the effect of revascularization procedures on foot perfusion. Future studies should focus on the use of this technique in predicting favorable outcome of revascularization procedures.

BackgroundIn diagnosing peripheral arterial disease (PAD), medial arterial calcification (MAC) hampers arterial compression and could lead to unreliable ankle brachial index (ABI), toe brachial index (TBI) and toe pressure (TP). Doppler ultrasonography (DUS) derived maximal systolic acceleration (ACCmax) might be more accurate to diagnose PAD. In an in vitro study, a strong correlation between ACCmax and the severity of stenotic disease was determined. The aim of this study was to investigate the ACCmax in correlation with conventional non-invasive diagnostics in an in vivo setting. Methods: In twelve healthy individuals, an arterial stenosis was mimicked by compression on the common femoral artery by an ultrasounds probe, creating a local stenosis of 50%, 70% and 90%. The ABI, TBI, TP and several DUS parameters (including ACCmax) were assessed at the ankle during these different degrees of stenosis. All DUS parameters were measured separately by two observers to determine the interobserver variability. Results: Overall the ABI, TBI, TP, ACCmax, ACCsys and PSV decreased significantly when the degree of stenosis increased. The ACCmax showed the highest correlation with the degree of stenosis (r -.884), compared to ABI (r -.726), TBI (r -.716) and TP (r -.758). Furthermore, the interobserver variability of ACCmax was excellent, with an intraclass correlation coefficient (ICC) of .97. Conclusion: ACCmax is an accurate non-invasive DUS parameter to diagnose and assess the severity of a mimicked arterial stenosis in healthy individuals. Further prospective assessment of the clinical value of ACCmax and its potential benefits in patients with PAD is needed.

Background: Patients with chronic limb threatening ischemia have a risk of undergoing a major amputation within 1 year of nearly 30% with a substantial risk of re-amputation since wound healing is often impaired. Quantitative assessment of regional tissue viability following amputation surgery can identify patients at risk for impaired wound healing. In quantification of regional tissue perfusion, near-infrared (NIR) fluorescence imaging using Indocyanine Green (ICG) seems promising., Methods: This pilot study included adult patients undergoing lower extremity amputation surgery due to peripheral artery disease or diabetes mellitus. ICG NIR fluorescence imaging was performed within 5 days following amputation surgery using the Quest Spectrum Platform Ⓡ . Following intravenous administration of ICG, the NIR fluorescence intensity of the amputation wound was recorded for 10 minutes. The NIR fluorescence intensity videos were analyzed and if a fluorescence deficit was observed, this region was marked as "low fluorescence." All other regions were marked as "normal fluorescence.", Results: Successful ICG NIR fluorescence imaging was performed in 10 patients undergoing a total of 15 amputations. No "low fluorescence" regions were observed in 11 out of 15 amputation wounds. In 10 out of these 11 amputations, no wound healing problems occurred during follow-up. Regions with "low fluorescence" were observed in 4 amputation wounds. Impaired wound healing corresponding to these regions was observed in all wounds and a re-amputation was necessary in 3 out of 4. When observing time-related parameters, regions with low fluorescence had a significantly longer time to maximum intensity (113 seconds vs. 32 seconds, P = 0.003) and a significantly lesser decline in outflow after five minutes (80.3% vs. 57.0%, P = 0.003)., Conclusions: ICG NIR fluorescence imaging was able to predict postoperative skin necrosis in all four cases. Quantitative assessment of regional perfusion remains challenging due toinfluencing factors on the NIR fluorescence intensity signal, including camera angle, camera distance and ICG dosage. This was also observed in this study, contributing to a large variety in fluorescence intensity parameters among patients. To provide surgeons with reliable NIR fluorescence cut-off values for prediction of wound healing, prospective studies on the intra-operative use of this technique are required. The potential prediction of wound healing using ICG NIR fluorescence imaging will have a huge impact on patient mortality, morbidity as well as the burden of amputation surgery on health care., (Copyright © 2021. Published by Elsevier Inc.)

Background: Because of the presence of medial calcific sclerosis, both ankle-branchial index and toe pressure measures can yield misleading results when attempting to diagnose peripheral artery disease (PAD). A new ultrasound parameter, maximal systolic acceleration (ACC max ), can be an accurate tool for diagnosing PAD, including in diabetic patients. However, it has not been evaluated thoroughly. The aim of this study was to assess the feasibility of using ACC max to diagnose and assess the severity of PAD., Methods: The human circulatory system was simulated using an in vitro circulatory system driven by a pulsatile pneumatic pump. Arterial stenosis of various degrees (50%, 70%, 80%, and 90%) was simulated in order to investigate the change in several ultrasound parameters (including ACC max ), as well as the intraluminal mean arterial pressure gradient. In a separate set of measurements, interobserver variability was measured using two investigators who were unaware of the degree of stenosis., Results: ACC max significantly decreased (P < .001), and the pressure gradient increased (P < .001) as the degree of stenosis increased. Moreover, we found a strong correlation between ACC max and the pressure gradient (R 2  = 0.937). Finally, interobserver variability with respect to ACC max was extremely low, with an intraclass correlation coefficient of 0.99., Conclusions: The results of this flow model study suggest that ACC max can be a valid, noninvasive tool for diagnosing PAD. Moreover, our finding that ACC max decreases as the severity of stenosis increases, together with the strong correlation between ACC max and the pressure gradient, suggests that ACC max may be useful as an alternative diagnostic tool for assessing the severity of PAD. These promising in vitro data warrant further study in a clinical setting., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: In the diagnosis of peripheral artery disease (PAD), the ankle-brachial index plays an important role. However, results of the ankle-brachial index are unreliable in patients with severe media sclerosis. Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) can provide information about tissue perfusion and has already been studied in oncologic, reconstructive, and cardiac surgery. For patients with PAD, this technique might give insight into skin perfusion and thereby guide treatment. We performed a systematic review of the literature on the use of NIR fluorescence imaging in patients with PAD., Methods: PubMed, MEDLINE, Embase, and Cochrane were searched for articles and abstracts on the application of NIR fluorescence imaging using ICG as fluorescent dye in patients with PAD. Our search strategy combined the terms "fluorescence," "ICG," or synonyms and "peripheral artery disease" or synonyms. The extracted data included fluorescence parameters and test characteristics for diagnosis of PAD., Results: Twenty-three articles were found eligible for this review using 18 different parameters for evaluation of the fluorescence signal intensity. NIR fluorescence imaging was used for four main indications: diagnosis, quality control in revascularization, guidance in amputation surgery, and visualization of vascular structures. For the diagnosis of PAD, NIR fluorescence imaging yields a sensitivity ranging from 67% to 100% and a specificity varying between 72% and 100%. Significant increases in multiple fluorescence parameters were found in comparing patients before and after revascularization., Conclusions: NIR fluorescence imaging can be used for several indications in patients with PAD. NIR fluorescence imaging seems promising in diagnosis of PAD and guidance of surgeons in treatment, especially in patients in whom current diagnostic methods are not applicable. Further standardization is needed to reliably use this modality in patients with PAD., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Prospects for no-option, end-stage peripheral artery disease (PAD) patients remain poor. Although results from open and semiblinded studies fuel hope for cell-based strategies in no-option patients, so far conclusions from the available placebo-controlled studies are not supportive. With the intention to end the remaining controversy with regard to cell therapy for PAD we conducted a confirmatory, double-blinded randomized placebo-controlled phase 3 trial., Study Design: This randomized controlled trial was registered (NCT00539266). Inclusion criteria included stable or progressive disabling PAD, no imminent need for amputation, absent accepted options for revascularization. Diabetic disease was an exclusion criterion. Bone marrow (500-700 mL) was harvested and bone marrow-derived mononuclear cells were concentrated to 40 mL. Concentrated cells or placebo (diluted blood) were intramuscularly injected at 40 locations of the calf muscle., Results: Fifty-four patients (mean (sd) age 58.2 (14.2) yrs, 58% males) were randomized. Twenty-eight patients received BM-MNCs, 26 placebo. Baseline criteria were similar in the 2 groups. No significant differences were observed for the primary (number of amputations, (pain free) walking distance) and secondary outcome parameters (ankle brachial index, pain scores, quality of life (SF-36))., Discussion: This fully blinded replication trial of autologous BM-MNC fails to confirm a benefit for cell therapy in no-option PAD patients, consequently BM-MNC therapy should not be offered as a clinical treatment. Apparent contrasting conclusions from open and controlled studies underscore the importance of a controlled trial design in evaluating cell-based interventions in PAD.

Background: Duplex ultrasonography (DUS) can be used for treatment planning for lower extremity peripheral arterial disease (PAD), but has not replaced contrast-enhanced imaging such as computed tomography angiography (CTA). We assessed DUS-based treatment planning for consistency, confidence, and the value of additional CTA among multinational surgeons., Methods: Data from 12 patients with PAD were reviewed by 2 American vascular surgeons individually and 1 Dutch vascular department by consensus. Reviewers selected treatment based on DUS first and based on added CTA second. Agreement and consistency of treatment plans was assessed using kappa statistics (κ). Imaging quality and therapeutic confidence were scored (1-5) and assessed with t-tests., Results: Of the 36 treatment plans formulated, additional CTA confirmed 27 (75%), changed 6 (17%), and supplemented 3 (8%) plans. The approach never changed when open revascularization was selected based on DUS (14 plans; 39%). Agreement between DUS- and CTA-based treatment planning was substantial, with a mean kappa (μκ) of 0.68, but agreement between reviewers was fair (μκ DUS, 0.24; μκ CTA, 0.23). CTA received greater average scores than DUS for quality (4.36 vs 3.29; P < .0001) and confidence (4.36 vs 3.26; P < .0001). Reviewers often expressed the need for additional imaging after DUS (mean, 63%)., Conclusion: PAD treatment planning based on CTA was mostly consistent with DUS-based treatment plans, although CTA was still felt to be needed to increase confidence. This observation suggests that to promote greater use of less invasive DUS imaging, not only improvement of DUS quality but also improvement of clinician confidence is required., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Objective: The value and cost-effectiveness of less invasive alternative imaging (AI) modalities (duplex ultrasound scanning, computed tomography angiography, and magnetic resonance angiography) in the care of peripheral arterial disease (PAD) has been reported; however, there is no consensus on their role. We hypothesized that AI utilization is low compared with angiography in the United States and that patient and hospital characteristics are both associated with AI utilization., Methods: The Nationwide Inpatient Sample (2007-2010) was used to identify patients with an International Classification of Diseases-Ninth Edition diagnosis of claudication or critical limb ischemia (CLI) as well as PAD treatment (surgical, endovascular, or amputation). Patients with AI and those with angiography or expected angiography (endovascular procedures without imaging codes) were selected and compared. Multivariable logistic regression was performed for receiving AI stratified by claudication and CLI and adjusting for patient and hospital factors., Results: We identified 290,184 PAD patients, of whom 5702 (2.0%) received AI. Patients with AI were more likely to have diagnosis of CLI (78.8% vs 48.6%; P < .0001) and receive open revascularizations (30.4% vs 18.8%; P < .0001). Van Walraven comorbidity scores (mean [standard error] 5.85 ± 0.22 vs 4.10 ± 0.05; P < .0001) reflected a higher comorbidity burden in AI patients. In multivariable analysis for claudicant patients, AI was associated with large bed size (odds ratio [OR], 3.26, 95% confidence interval [CI], 1.16-9.18; P = .025), teaching hospitals (OR, 1.97; 95% CI, 1.10-3.52; P = .023), and renal failure (OR, 1.52; 95% CI, 1.13-2.05; P = .006). For CLI patients, AI was associated with black race (OR, 1.53; 95% CI, 1.13-2.08; P = .006) and chronic heart failure (OR, 1.29; 95% CI, 1.04-1.60; P = .021) and was negatively associated with renal failure (OR, 0.80; 95% CI, 0.67-0.95; P = .012). The Northeast and West regions were associated with higher odds of AI in claudicant patients (OR, 2.41; 95% CI, 1.23-4.75; P = .011; and OR, 2.59; 95% CI, 1.34-5.02; P = .005, respectively) and CLI patients (OR, 4.31; 95% CI, 2.20-8.36; P < .0001; and OR, 2.18; 95% CI, 1.12-4.22; P = .021, respectively). Rates of AI utilization across states were not evenly distributed but showed great variability, with ranges from 0.31% to 9.81%., Conclusions: National utilization of AI for PAD is low and shows great variation among institutions in the United States. Patient and hospital factors are both associated with receiving AI in PAD care, and AI utilization is subject to significant regional variation. These findings suggest differences in systems of care or practice patterns and call for a clearer understanding and a more unified approach to imaging strategies in PAD care., (Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Objectives: This study aims to provide insight into cellular kinetics using molecular imaging after different transplantation methods of bone marrow-derived mononuclear cells (MNCs) in a mouse model of peripheral artery disease (PAD)., Background: MNC therapy is a promising treatment for PAD. Although clinical translation has already been established, there is a lack of knowledge about cell behavior after transplantation and about the mechanism whereby MNC therapy might ameliorate complaints of PAD., Methods: MNCs were isolated from F6 transgenic mice (FVB background) that express firefly luciferase (Fluc) and green fluorescence protein (GFP). Male FVB and C57Bl6 mice (n = 50) underwent femoral artery ligation and were randomized into 4 groups receiving the following: 1) single intramuscular (IM) injection of 2 × 10(6) MNCs; 2) 4 weekly IM injections of 5 × 10(5) MNCs; 3) 2 × 10(6) MNCs intravenously; and 4) phosphate-buffered saline as control. Cells were characterized by flow cytometry and in vitro bioluminescence imaging (BLI). Cell survival, proliferation, and migration were monitored by in vivo BLI, which was validated by ex vivo BLI, post-mortem immunohistochemistry, and flow cytometry. Paw perfusion and neovascularization was measured with laser Doppler perfusion imaging (LDPI) and histology, respectively., Results: In vivo BLI revealed near-complete donor cell death 4 weeks after IM transplantation. After intravenous transplantation, BLI revealed that cells migrated to the injured area in the limb, as well as to the liver, spleen, and bone marrow. Ex vivo BLI showed presence of MNCs in the scar tissue and adductor muscle. However, no significant effects on neovascularization were observed, as monitored by LDPI and histology., Conclusions: This is one of the first studies to assess kinetics of transplanted MNCs in PAD using in vivo molecular imaging. MNC survival is short-lived, MNCs do not preferentially home to injured areas, and MNCs do not significantly stimulate perfusion in this particular model., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to validate a Dutch translation of the Cardiff wound impact schedule (CWIS), a disease‐specific instrument to measure the health‐related quality of life (HRQoL) in patients with chronic leg ulcers. To achieve this, the original instrument was translated. A total of 83 patients with chronic lower leg ulcers were included and completed the translated instrument and SF36 at baseline after assessment of their wound severity. Follow‐up was performed 1 week after inclusion. The psychometric properties of the instrument were assessed. Construct validity was positively evaluated by an expert panel. Face validity was positively evaluated in a cognitive debriefing of a pilot group. Discriminant validity was assessed by correlating 1‐year amputation risk according to the Wound, Ischaemia, foot Infection classification system with the instrument scores. Significant correlation could not be proven. Criterion validity was assessed by correlating domain scores of the instrument with domain scores of the gold standard: SF36. Moderate to high correlation was calculated for most domains of the instrument. Test‐retest reliability and internal consistency were evaluated as acceptable. In conclusion, the Dutch translation of the CWIS is a valid and reliable disease‐specific instrument to assess the HRQoL in patients with chronic lower leg ulcers. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Social support may influence the seeking of appropriate treatment. We examined social support and peripheral arterial disease (PAD) severity as determinants of treatment for PAD in younger and older patients. Methods: Consecutive PAD patients (N=203) completed the Perceived Social Support Scale. Treadmill-walking distance and ankle–brachial pressure index (ABPI) were measured. The main outcome was invasive treatment for PAD in the year following diagnosis. Results: During follow-up, 48% of the patients underwent invasive treatment for PAD. Younger patients (≤64 years) tended to be more often invasively treated as compared to older patients. In younger patients, a high level of social support predicted invasive treatment above and beyond PAD severity. In older patients, low ABPI predicted invasive treatment. Conclusion: Younger patients with inadequate social support may fail to seek appropriate treatment, suggesting the need to consider psychosocial factors in optimizing treatment of atherosclerotic vascular disease in this high-risk group. [Copyright &y& Elsevier]