Peripheral Artery Disease: From Diagnosis to Treatment

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Vascular Medicine".

Deadline for manuscript submissions: closed (10 January 2022) | Viewed by 52887

Special Issue Editor


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Guest Editor
CHU Rennes, Unité Médecine Vasculaire, 2 Rue Henri Le Guilloux, F-35033 Rennes, France.
Interests: peripheral artery disease; activity monitor; doppler waveforms; oximetry, diagnosis tests

Special Issue Information

Dear Colleagues,

This Special Issue will focus on the management of lower extremity peripheral artery disease (PAD). More than 230 million people worldwide suffer from PAD, which remains underdiagnosed. The clinical spectrum of the disease is broad: some patients will have no symptoms whereas others will experience exertional limb symptoms or wounds. Different tools can be used by clinicians to make a diagnosis depending on the disease stage. Despite the increasing interest in PAD management over the past decade, with randomized controlled trials focusing on patients with PAD, there is still a lot to be done.

This issue aims to provide an update of the clinical management of PAD but also provide a forum for the discussion of original perspectives (health policies, e-health, etc.) from the diagnosis to the treatment of PAD, in order to improve clinical practice.

We are looking for original articles and reviews dealing with diagnostic approaches, treatments, and all the different aspects of PAD management.

Prof. Guillaume Mahe
Guest Editor

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Keywords

  • peripheral artery disease
  • ankle–brachial index
  • medical therapy
  • endovascular therapy
  • exercise therapy
  • diet
  • diagnosis methods

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Published Papers (15 papers)

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Research

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12 pages, 1453 KiB  
Article
The Influence of Treadmill Training on the Bioelectrical Activity of the Lower Limb Muscles in Patients with Intermittent Claudication
by Anna Mika, Piotr Mika, Łukasz Oleksy and Anita Kulik
J. Clin. Med. 2022, 11(5), 1302; https://doi.org/10.3390/jcm11051302 - 27 Feb 2022
Viewed by 1573
Abstract
Aim: Intermittent claudication is the most common symptomatic manifestation of peripheral arterial disease (PAD), presenting as ischemic leg muscle pain and gait dysfunction. The aim of this study was to evaluate the changes in bioelectrical activity of the lower limb muscles activity in [...] Read more.
Aim: Intermittent claudication is the most common symptomatic manifestation of peripheral arterial disease (PAD), presenting as ischemic leg muscle pain and gait dysfunction. The aim of this study was to evaluate the changes in bioelectrical activity of the lower limb muscles activity in claudicating patients over a 12-week period of supervised treadmill training and to verify the hypothesis as to which muscles of lower limbs are activated by training treatment—the proximal, as compensatory mechanism, or the distal, which are the most ischemic. Methods: The study comprised 45 patients aged 60–70 years (height 168.8 ± 6.8 cm, weight 78.9 ± 9.2 kg) with PAD and unilateral intermittent claudication (Fontaine stage IIa/IIb), who participated in a 12-week supervised treadmill training program. Surface electromyography (sEMG) of the gastrocnemius lateralis (GaL), gastrocnemius medialis (GaM), tibialis anterior (TA), biceps femoris (BF), rectus femoris (RF) and gluteus medius (GM) muscles in the claudicated leg were continuously measured during the treadmill test. The average mean amplitude and mean amplitude range of the sEMG signal were analyzed. Results: During the treadmill test, after 12 weeks of training, the average mean amplitude of the GM (105 ± 43 vs. 74 ± 38%, p = 0.000008, ES = 0.76), BF (41 ± 22 vs. 33 ± 12%, p = 0.006, ES = 0.45) and GaM (134 ± 50 vs. 114 ± 30%, p = 0.007, ES = 0.48) muscles was significantly lower compared with baseline. The mean amplitude range was significantly decreased after 12 weeks of training in the GM (229 ± 64 vs. 181 ± 62%, p = 0.008, ES = 0.77) and BF (110 ± 69 vs. 84 ± 31%, p = 0.0002, ES = 0.48) muscles. After 12 weeks of training, the mean amplitude range of the TA muscle was significantly higher compared with baseline (104 ± 46 vs. 131 ± 53%, p = 0.001, ES = 0.54), but without significant changes in the average mean amplitude value. The most favorable changes, suggesting the lowest muscle fatigue and the highest walking capacity, were found in patients with the longest walking time. Conclusions: The obtained results may suggest that after 12 weeks of treadmill training, beneficial changes occurred in both the proximal and distal muscles. Therefore, greater foot plantar flexion and stronger push-off as well as greater hip extension may be considered the main mechanisms of observed gait pattern improvement. It may also be suggested that the therapy of gait alterations in patients with PAD should be focused not only on calf muscle pump improvement, but also on proximal hip extensor strengthening. Full article
(This article belongs to the Special Issue Peripheral Artery Disease: From Diagnosis to Treatment)
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10 pages, 594 KiB  
Article
Use of a Pre-Trained Neural Network for Automatic Classification of Arterial Doppler Flow Waveforms: A Proof of Concept
by Antoine Guilcher, Damien Laneelle and Guillaume Mahé
J. Clin. Med. 2021, 10(19), 4479; https://doi.org/10.3390/jcm10194479 - 28 Sep 2021
Cited by 1 | Viewed by 2348
Abstract
Background: Arterial Doppler flow waveform analysis is a tool recommended for the management of lower extremity peripheral arterial disease (PAD). To standardize the waveform analysis, classifications have been proposed. Neural networks have shown a great ability to categorize data. The aim of the [...] Read more.
Background: Arterial Doppler flow waveform analysis is a tool recommended for the management of lower extremity peripheral arterial disease (PAD). To standardize the waveform analysis, classifications have been proposed. Neural networks have shown a great ability to categorize data. The aim of the present study was to use an existing neural network to evaluate the potential for categorization of arterial Doppler flow waveforms according to a commonly used classification. Methods: The Pareto efficient ResNet-101 (ResNet-101) neural network was chosen to categorize 424 images of arterial Doppler flow waveforms according to the Simplified Saint-Bonnet classification. As a reference, the inter-operator variability between two trained vascular medicine physicians was also assessed. Accuracy was expressed in percentage, and agreement was assessed using Cohen’s Kappa coefficient. Results: After retraining, ResNet-101 was able to categorize waveforms with 83.7 ± 4.6% accuracy resulting in a kappa coefficient of 0.79 (0.75–0.83) (CI 95%), compared with a kappa coefficient of 0.83 (0.79–0.87) (CI 95%) between the two physicians. Conclusion: This study suggests that the use of transfer learning on a pre-trained neural network is feasible for the automatic classification of images of arterial Doppler flow waveforms. Full article
(This article belongs to the Special Issue Peripheral Artery Disease: From Diagnosis to Treatment)
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10 pages, 267 KiB  
Article
Improvement in 6-Minute Walking Distance after Supervised Exercise Training Is Related to Changes in Quality of Life in Patients with Lower Extremity Peripheral Artery Disease
by Stefano Lanzi, Luca Calanca, André Berchtold and Lucia Mazzolai
J. Clin. Med. 2021, 10(15), 3330; https://doi.org/10.3390/jcm10153330 - 28 Jul 2021
Cited by 16 | Viewed by 2166
Abstract
This study aimed to investigate the relationship between supervised exercise training (SET)-induced changes in treadmill performance and 6 min walking distance, and changes in general (physical and mental) self-perceived health-related quality of life (HRQoL) in symptomatic patients with lower extremity peripheral artery disease [...] Read more.
This study aimed to investigate the relationship between supervised exercise training (SET)-induced changes in treadmill performance and 6 min walking distance, and changes in general (physical and mental) self-perceived health-related quality of life (HRQoL) in symptomatic patients with lower extremity peripheral artery disease (PAD). This is an observational study investigating Fontaine stage II PAD patients participating in 3-month SET. Before and following SET, treadmill performance (pain-free (PFWD) and maximal (MWD)), and 6 min walking distance (6MWD) were assessed. Self-perceived HRQoL was assessed with the Medical Outcomes Study Short-Form 36 (SF-36). Ankle- and toe-brachial indexes were also measured. One-hundred forty-seven patients with PAD were included (64.9 ± 9.6 y, 70% men). After SET, PFWD (+102%, p ≤ 0.001), MWD (+87%, p ≤ 0.001), and 6MWD (+14%, p ≤ 0.001) significantly increased. All eight SF-36 subscale scores significantly improved following SET (p ≤ 0.04). SET significantly improved physical and mental component summaries of the SF-36 (p ≤ 0.001). Larger increases in 6MWD were associated with greater improvements in physical (β = 0.19; p = 0.02) and mental (β = 0.24; p = 0.005) component summaries of the SF-36. No significant relationship was observed between changes in treadmill performance and changes in physical and mental component summaries of the SF-36. These results show that improvements in 6MWD following SET are related to improvements in general self-perceived HRQoL in patients with symptomatic lower extremity PAD. On the contrary, changes in treadmill performance were not related to improvements in HRQoL. These results suggest that the 6 min walking test is an essential outcome measure to assess overall patient functional status following interventions in patients with PAD. Full article
(This article belongs to the Special Issue Peripheral Artery Disease: From Diagnosis to Treatment)
7 pages, 245 KiB  
Article
Gender Differences in the Medical Treatment of Peripheral Artery Disease
by Damien Lanéelle, Gabriella Sauvet, Jérôme Guillaumat, Jean Eudes Trihan and Guillaume Mahé
J. Clin. Med. 2021, 10(13), 2855; https://doi.org/10.3390/jcm10132855 - 28 Jun 2021
Cited by 9 | Viewed by 1903
Abstract
Background/Objectives: Peripheral arterial disease is a frequent and severe disease with high cardiovascular morbidity and mortality. However, female patients appear to be undertreated. Objectives: The primary goal was to compare the prescription of optimal medical treatment (OMT) of peripheral arterial disease between women [...] Read more.
Background/Objectives: Peripheral arterial disease is a frequent and severe disease with high cardiovascular morbidity and mortality. However, female patients appear to be undertreated. Objectives: The primary goal was to compare the prescription of optimal medical treatment (OMT) of peripheral arterial disease between women and men in primary health care. Material and methods: An observational retrospective study was based on the data collected from general practitioners (GP) office in Brittany. Results: The study included 100 patients, aged 71 ± 10 years old, with 24% of women. Compared to men, women received the OMT less frequently (29.2% vs. 53.9%, p = 0.038), especially after 75 years old. Antiplatelet therapy was largely prescribed (100%), statins less frequently (70.8% women vs. 85.5% men), and prescription of renin-angiotensin-aldosterone system inhibitors was still not optimal in the two genders (41.7% women vs. 61.9% men). Active smoking is important for both women and men (33% and 30% respectively). Conclusion: Optimal medical treatment of peripheral artery disease is insufficiently prescribed, especially in women in this region of France. Full article
(This article belongs to the Special Issue Peripheral Artery Disease: From Diagnosis to Treatment)
12 pages, 257 KiB  
Article
Multimodal Supervised Exercise Training Is Effective in Improving Long Term Walking Performance in Patients with Symptomatic Lower Extremity Peripheral Artery Disease
by Barbara Ney, Stefano Lanzi, Luca Calanca and Lucia Mazzolai
J. Clin. Med. 2021, 10(10), 2057; https://doi.org/10.3390/jcm10102057 - 11 May 2021
Cited by 11 | Viewed by 2334
Abstract
This study aimed to evaluate the effect of a multimodal supervised exercise training (SET) program on walking performance for 12 months in patients with symptomatic lower extremity peripheral artery disease (PAD). Consecutive patients with Fontaine stage II PAD participating in the SET program [...] Read more.
This study aimed to evaluate the effect of a multimodal supervised exercise training (SET) program on walking performance for 12 months in patients with symptomatic lower extremity peripheral artery disease (PAD). Consecutive patients with Fontaine stage II PAD participating in the SET program of our hospital were retrospectively investigated. Walking performance, assessed using a treadmill with measures of the pain-free and maximal walking distance (PFWD, MWD, respectively), and 6 min walking distance (6MWD), were tested before and following SET, as well as at 6 and 12 months after SET completion. Ninety-three symptomatic patients with PAD (65.0 ± 1.1 y) were included in the study. Following SET, the walking performance significantly improved (PFWD: +145%, p ≤ 0.001; MWD: +97%, p ≤ 0.001; 6MWD: +15%, p ≤ 0.001). At 6 months, PFWD (+257%, p ≤ 0.001), MWD (+132%, p ≤ 0.001), and 6MWD (+11%, p ≤ 0.001) remained significantly improved compared with the pre-SET condition. At 12 months, PFWD (+272%, p ≤ 0.001), MWD (+130%, p ≤ 0.001), and 6MWD (+11%, p ≤ 0.001) remained significantly improved compared with the pre-training condition. The walking performance remained significantly improved in both women and men for up to 12 months (p ≤ 0.001). Multimodal SET is effective at improving walking performance in symptomatic patients with PAD, with improvements lasting up to 12 months. Full article
(This article belongs to the Special Issue Peripheral Artery Disease: From Diagnosis to Treatment)
11 pages, 1124 KiB  
Article
Comparison of the Use of Arterial Doppler Waveform Classifications in Clinical Routine to Describe Lower Limb Flow
by Antoine Guilcher, Damien Lanéelle, Clément Hoffmann, Jérôme Guillaumat, Joel Constans, Luc Bressollette, Claire Le Hello, Christian Boissier, Alessandra Bura-Rivière, Vincent Jaquinandi, Loukman Omarjee, Philippe Lacroix, Gilles Pernod, Fabrice Abbadie, Marie Antoinette Sevestre, Carine Boulon and Guillaume Mahé
J. Clin. Med. 2021, 10(3), 464; https://doi.org/10.3390/jcm10030464 - 26 Jan 2021
Cited by 6 | Viewed by 11630
Abstract
Background: Characterisation of arterial Doppler waveforms is a persistent problem and a source of confusion in clinical practice. Classifications have been proposed to address the problem but their efficacy in clinical practice is unknown. The aim of the present study was to compare [...] Read more.
Background: Characterisation of arterial Doppler waveforms is a persistent problem and a source of confusion in clinical practice. Classifications have been proposed to address the problem but their efficacy in clinical practice is unknown. The aim of the present study was to compare the efficacy of the categorisation rate of Descotes and Cathignol, Spronk et al. and the simplified Saint-Bonnet classifications. Methods: This is a multicentre prospective study where 130 patients attending a vascular arterial ultrasound were enrolled and Doppler waveform acquisition was performed at the common femoral, the popliteal, and the distal arteries at both sides. Experienced vascular specialists categorized these waveforms according to the three classifications. Results: of 1033 Doppler waveforms, 793 (76.8%), 943 (91.3%) and 1014 (98.2%) waveforms could be categorized using Descotes and Cathignol, Spronk et al. and the simplified Saint-Bonnet classifications, respectively. Differences in categorisation between classifications were significant (Chi squared test, p < 0.0001). Of 19 waveforms uncategorized using the simplified Saint-Bonnet classification, 58% and 84% were not categorized using the Spronk et al. and Descotes and Cathignol classifications, respectively. Conclusions: The results of the present study suggest that the simplified Saint-Bonnet classification provides a superior categorisation rate when compared with Spronk et al. and Descotes and Cathignol classifications. Full article
(This article belongs to the Special Issue Peripheral Artery Disease: From Diagnosis to Treatment)
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16 pages, 10544 KiB  
Article
Fibrosis Distinguishes Critical Limb Ischemia Patients from Claudicants in a Transcriptomic and Histologic Analysis
by Guangzhi Cong, Xiangdong Cui, Ricardo Ferrari, Iraklis I. Pipinos, George P. Casale, Ansuman Chattopadhyay and Ulka Sachdev
J. Clin. Med. 2020, 9(12), 3974; https://doi.org/10.3390/jcm9123974 - 8 Dec 2020
Cited by 12 | Viewed by 2834
Abstract
Most patients with critical limb ischemia (CLI) from peripheral arterial disease (PAD) do not have antecedent intermittent claudication (IC). We hypothesized that transcriptomic analysis would identify CLI-specific pathways, particularly in regards to fibrosis. Derivation cohort data from muscle biopsies in PAD and non-PAD [...] Read more.
Most patients with critical limb ischemia (CLI) from peripheral arterial disease (PAD) do not have antecedent intermittent claudication (IC). We hypothesized that transcriptomic analysis would identify CLI-specific pathways, particularly in regards to fibrosis. Derivation cohort data from muscle biopsies in PAD and non-PAD (controls) was obtained from the Gene Expression Omnibus (GSE120642). Transcriptomic analysis indicated CLI patients (N = 16) had a unique gene expression profile, when compared with non-PAD controls (N = 15) and IC (N = 20). Ninety-eight genes differed between controls and IC, 2489 genes differed between CLI and controls, and 2783 genes differed between CLI and IC patients. Pathway enrichment analysis showed that pathways associated with TGFβ, collagen deposition, and VEGF signaling were enriched in CLI but not IC. Receiver operating curve (ROC) analysis of nine fibrosis core gene expression revealed the areas under the ROC (AUC) were all >0.75 for CLI. Furthermore, the fibrosis area (AUC = 0.81) and % fibrosis (AUC = 0.87) in validation cohort validated the fibrosis discrimination CLI from IC and control (all n = 12). In conclusion, transcriptomic analysis identified fibrosis pathways, including those involving TGFβ, as a novel gene expression feature for CLI but not IC. Fibrosis is an important characteristic of CLI, which we confirmed histologically, and may be a target for novel therapies in PAD. Full article
(This article belongs to the Special Issue Peripheral Artery Disease: From Diagnosis to Treatment)
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10 pages, 1937 KiB  
Article
Individuals with Peripheral Artery Disease (PAD) and Type 1 Diabetes Are More Likely to Undergo Limb Amputation than Those with PAD and Type 2 Diabetes
by Nidhi Jain, Manyoo A. Agarwal, Diana Jalal and Ayotunde O. Dokun
J. Clin. Med. 2020, 9(9), 2809; https://doi.org/10.3390/jcm9092809 - 31 Aug 2020
Cited by 7 | Viewed by 2607
Abstract
Background: Limited data exist comparing how type 1 diabetes mellitus (DM) and type 2 DM may have differential effects on peripheral artery disease (PAD) severity. We aimed to study the association of type of DM with the procedure utilized in hospitalizations with a [...] Read more.
Background: Limited data exist comparing how type 1 diabetes mellitus (DM) and type 2 DM may have differential effects on peripheral artery disease (PAD) severity. We aimed to study the association of type of DM with the procedure utilized in hospitalizations with a diagnosis of PAD. Methods: We used the national inpatient sample databases from 2003 to 2014 to identify hospitalizations with a diagnosis of PAD and type 1 or type 2 DM. Logistic regression was utilized to evaluate the association between type of DM and procedure utilized (amputation-overall, major, endovascular revascularization, surgical revascularization). Results: We identified 14,012,860 hospitalizations with PAD diagnosis and DM, 5.6% (n = 784,720) had type 1 DM. The patients with type 1 DM were more likely to present with chronic limb-threatening ischemia (CLTI) (45.2% vs. 32.0%), ulcer (25.9% vs. 17.7%), or complicated ulcer (16.6% vs. 10.5%) (all p < 0.001) when compared to those with type 2 DM. Type 1 DM was independently and significantly associated with more amputation procedures (adjusted odds ratio = 1.12, 95% confidence interval [CI] I 1.08 to 1.16, p < 0.001). Overall, in-hospital mortality did not differ between the individuals with type 1 and type 2 DM. The overall mean (95% CI) length of stay (in days) was 6.6 (6.5 to 6.6) and was significantly higher for type 1 DM (7.8 [7.7 to 8.0]) when compared to those with type 2 DM (6.5 [6.4 to 6.6]). Conclusion: We observed that individuals with PAD and type 1 DM were more likely to present with CLTI and ulcer and undergo amputation when compared to those with PAD and type 2 diabetes. Further studies are needed to better understand the underlying mechanisms behind these findings and to identify novel interventions to reduce the risk of amputation in patients with type 1 DM. Full article
(This article belongs to the Special Issue Peripheral Artery Disease: From Diagnosis to Treatment)
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20 pages, 4035 KiB  
Article
Abnormal Microvascular Architecture, Fibrosis, and Pericyte Characteristics in the Calf Muscle of Peripheral Artery Disease Patients with Claudication and Critical Limb Ischemia
by Constance J. Mietus, Timothy J. Lackner, Petros S. Karvelis, Gregory T. Willcockson, Christina M. Shields, Nicholas G. Lambert, Panagiotis Koutakis, Matthew A. Fuglestad, Hernan Hernandez, Gleb R. Haynatzki, Julian K. S. Kim, Holly K. DeSpiegelaere, Iraklis I. Pipinos and George P. Casale
J. Clin. Med. 2020, 9(8), 2575; https://doi.org/10.3390/jcm9082575 - 8 Aug 2020
Cited by 17 | Viewed by 2797
Abstract
Work from our laboratory documents pathological events, including myofiber oxidative damage and degeneration, myofibrosis, micro-vessel (diameter = 50–150 μm) remodeling, and collagenous investment of terminal micro-vessels (diameter ≤ 15 µm) in the calf muscle of patients with Peripheral Artery Disease (PAD). In this [...] Read more.
Work from our laboratory documents pathological events, including myofiber oxidative damage and degeneration, myofibrosis, micro-vessel (diameter = 50–150 μm) remodeling, and collagenous investment of terminal micro-vessels (diameter ≤ 15 µm) in the calf muscle of patients with Peripheral Artery Disease (PAD). In this study, we evaluate the hypothesis that the vascular pathology associated with the legs of PAD patients encompasses pathologic changes to the smallest micro-vessels in calf muscle. Biopsies were collected from the calf muscle of control subjects and patients with Fontaine Stage II and Stage IV PAD. Slide specimens were evaluated by Quantitative Multi-Spectral and Fluorescence Microscopy. Inter-myofiber collagen, stained with Masson Trichrome (MT), was increased in Stage II patients, and more substantially in Stage IV patients in association with collagenous thickening of terminal micro-vessel walls. Evaluation of the Basement Membrane (BM) of these vessels reveals increased thickness in Stage II patients, and increased thickness, diameter, and Collagen I deposition in Stage IV patients. Coverage of these micro-vessels with pericytes, key contributors to fibrosis and BM remodeling, was increased in Stage II patients, and was greatest in Stage IV patients. Vascular pathology of the legs of PAD patients extends beyond atherosclerotic main inflow arteries and affects the entire vascular tree—including the smallest micro-vessels. Full article
(This article belongs to the Special Issue Peripheral Artery Disease: From Diagnosis to Treatment)
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11 pages, 1020 KiB  
Article
Assessment of Mortality and Factors Affecting Outcome of Use of Paclitaxel-Coated Stents and Bare Metal Stents in Femoropopliteal PAD
by Aleksander Falkowski, Hubert Bogacki and Marcin Szemitko
J. Clin. Med. 2020, 9(7), 2221; https://doi.org/10.3390/jcm9072221 - 13 Jul 2020
Cited by 10 | Viewed by 2168
Abstract
The use of drug-coated devices in intravascular therapy is aimed at preventing neointimal hyperplasia caused by excessive proliferation of vascular smooth muscle and thereby restenosis. Although its use seemed initially promising, a recent publication has shown an increased risk of mortality with paclitaxel-coated [...] Read more.
The use of drug-coated devices in intravascular therapy is aimed at preventing neointimal hyperplasia caused by excessive proliferation of vascular smooth muscle and thereby restenosis. Although its use seemed initially promising, a recent publication has shown an increased risk of mortality with paclitaxel-coated devices, and there is an urgent need to reaffirm assessments of drug-eluting stents (DES). Objective: The aim of the study was to compare mortality and effectiveness of paclitaxel-coated stents and bare-metal stents (BMS) in the treatment of peripheral arterial disease (PAD) with long-term follow-up. Materials and methods: In a single center randomized study, 256 patients with PAD were treated intravascularly with stent implantation. Patients were randomized into two groups: the first (n = 126) were treated with DES, and the second (n = 130) were treated with BMS. The study included evaluation after the procedure, after about 6 months and 36 months. Co-morbidities, with risks for atherosclerosis, were analyzed in all patients. Patients were evaluated for clinical outcome, restenosis frequency, and safety (complications and total mortality). Results: Clinical benefit at the end of the investigation was statistically significantly better in the DES group compared with the BMS group: 85.7% versus 66.2% (p = 0.0003), respectively. Restenosis occurred significantly less frequently in patients with DES: 16.0% versus BMS: 35.0%, p = 0.012. There was no significant effect of comorbidities on the frequency of restenoses. There were no differences in all-cause mortality over the three years with paclitaxel and no-paclitaxel stents cohorts (8.7% versus 7.1%; long-rank p = 0.575). No association was found with mortality and treatment with DES or BMS. Conclusions: The use of paclitaxel-coated stents gave good clinical benefit and caused a significantly lower frequency of restenosis compared to bare-metal stents. The use of paclitaxel-coated stents did not increase mortality. Full article
(This article belongs to the Special Issue Peripheral Artery Disease: From Diagnosis to Treatment)
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24 pages, 4294 KiB  
Article
Serum Metabolic Signatures of Chronic Limb-Threatening Ischemia in Patients with Peripheral Artery Disease
by Sandi M. Azab, Abdelrahman Zamzam, Muzammil H. Syed, Rawand Abdin, Mohammad Qadura and Philip Britz-McKibbin
J. Clin. Med. 2020, 9(6), 1877; https://doi.org/10.3390/jcm9061877 - 16 Jun 2020
Cited by 25 | Viewed by 3948
Abstract
Peripheral artery disease (PAD) is characterized by the atherosclerotic narrowing of lower limb vessels, leading to ischemic muscle pain in older persons. Some patients experience progression to advanced chronic limb-threatening ischemia (CLTI) with poor long-term survivorship. Herein, we performed serum metabolomics to reveal [...] Read more.
Peripheral artery disease (PAD) is characterized by the atherosclerotic narrowing of lower limb vessels, leading to ischemic muscle pain in older persons. Some patients experience progression to advanced chronic limb-threatening ischemia (CLTI) with poor long-term survivorship. Herein, we performed serum metabolomics to reveal the mechanisms of PAD pathophysiology that may improve its diagnosis and prognosis to CLTI complementary to the ankle–brachial index (ABI) and clinical presentations. Non-targeted metabolite profiling of serum was performed by multisegment injection–capillary electrophoresis–mass spectrometry (MSI–CE–MS) from age and sex-matched, non-diabetic, PAD participants who were recruited and clinically stratified based on the Rutherford classification into CLTI (n = 18) and intermittent claudication (IC, n = 20). Compared to the non-PAD controls (n = 20), PAD patients had lower serum concentrations of creatine, histidine, lysine, oxoproline, monomethylarginine, as well as higher circulating phenylacetylglutamine (p < 0.05). Importantly, CLTI cases exhibited higher serum concentrations of carnitine, creatinine, cystine and trimethylamine-N-oxide along with lower circulating fatty acids relative to well matched IC patients. Most serum metabolites associated with PAD progression were also correlated with ABI (r = ±0.24−0.59, p < 0.05), whereas the ratio of stearic acid to carnitine, and arginine to propionylcarnitine differentiated CLTI from IC with good accuracy (AUC = 0.87, p = 4.0 × 10−5). This work provides new biochemical insights into PAD progression for the early detection and surveillance of high-risk patients who may require peripheral vascular intervention to prevent amputation and premature death. Full article
(This article belongs to the Special Issue Peripheral Artery Disease: From Diagnosis to Treatment)
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Review

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16 pages, 6181 KiB  
Review
Supervised Resistance Training on Functional Capacity, Muscle Strength and Vascular Function in Peripheral Artery Disease: An Updated Systematic Review and Meta-Analysis
by Elizabeth E. Blears, Jessica K. Elias, Christian Tapking, Craig Porter and Victoria G. Rontoyanni
J. Clin. Med. 2021, 10(10), 2193; https://doi.org/10.3390/jcm10102193 - 19 May 2021
Cited by 7 | Viewed by 2940
Abstract
Supervised resistance training appears to be a promising alternative exercise modality to supervised walking in patients with peripheral artery disease (PAD). This meta-analysis examined the efficacy of supervised RT for improving walking capacity, and whether adaptations occur at the vascular and/or skeletal muscle [...] Read more.
Supervised resistance training appears to be a promising alternative exercise modality to supervised walking in patients with peripheral artery disease (PAD). This meta-analysis examined the efficacy of supervised RT for improving walking capacity, and whether adaptations occur at the vascular and/or skeletal muscle level in PAD patients. We searched Medline, CINAHL, Scopus, and Cochrane Central Register of Controlled Trials databases for randomized controlled trials (RCTs) in PAD patients testing the effects of supervised RT for ≥4 wk. on walking capacity, vascular function, and muscle strength. Pooled effect estimates were calculated and evaluated using conventional meta-analytic procedures. Six RCTs compared supervised RT to standard care. Overall, supervised RT prolonged claudication onset distance during a 6-min walk test (6-MWT) (101.7 m (59.6, 143.8), p < 0.001) and improved total walking distance during graded treadmill walking (SMD: 0.67 (0.33, 1.01), p < 0.001) and the 6-MWT (49.4 m (3.1, 95.6), p = 0.04). Five RCTS compared supervised RT and supervised intermittent walking, where the differences in functional capacity between the two exercise modalities appear to depend on the intensity of the exercise program. The insufficient evidence on the effects of RT on vascular function and muscle strength permitted only limited exploration. We conclude that RT is effective in prolonging walking performance in PAD patients. Whether RT exerts its influence on functional capacity by promoting blood flow and/or enhancing skeletal muscle strength remains unclear. Full article
(This article belongs to the Special Issue Peripheral Artery Disease: From Diagnosis to Treatment)
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9 pages, 252 KiB  
Review
What Is Currently the Role of TcPO2 in the Choice of the Amputation Level of Lower Limbs? A Comprehensive Review
by Judith Catella, Anne Long and Lucia Mazzolai
J. Clin. Med. 2021, 10(7), 1413; https://doi.org/10.3390/jcm10071413 - 1 Apr 2021
Cited by 18 | Viewed by 2793
Abstract
Some patients still require major amputation for lower extremity peripheral arterial disease treatment. The purpose of pre-operative amputation level selection is to determine the most distal amputation site with the highest healing probability without re-amputation. Transcutaneous oximetry (TcPO2) can detect viable tissue with [...] Read more.
Some patients still require major amputation for lower extremity peripheral arterial disease treatment. The purpose of pre-operative amputation level selection is to determine the most distal amputation site with the highest healing probability without re-amputation. Transcutaneous oximetry (TcPO2) can detect viable tissue with the highest probability of healing. Several factors affect the accuracy of TcPO2; nevertheless, surgeons rely on TcPO2 values to determine the optimal amputation level. Background about the development of TcPO2, methods of measurement, consequences of lower limb amputation level, and the place of TcPO2 in the choice of the amputation level are reviewed herein. Most of the retrospective studies indicated that calf TcPO2 values greater than 40 mmHg were associated with a high percentage of successful wound healing after below-knee-amputation, whereas values lower than 20 mmHg indicated an increased risk of unsuccessful healing. However, a consensus on the precise cut-off value of TcPO2 necessary to assure healing is missing. Ways of improvement for TcPO2 performance applied to the optimization of the amputation-level are reported herein. Further prospective data are needed to better approach a TcPO2 value that will promise an acceptable risk of re-amputation. Standardized TcPO2 measurement is crucial to ensure quality of data. Full article
(This article belongs to the Special Issue Peripheral Artery Disease: From Diagnosis to Treatment)
14 pages, 925 KiB  
Review
The Acute Effect of Exercise on Arterial Stiffness in Healthy Subjects: A Meta-Analysis
by Alicia Saz-Lara, Iván Cavero-Redondo, Celia Álvarez-Bueno, Blanca Notario-Pacheco, Marta Carolina Ruiz-Grao and Vicente Martínez-Vizcaíno
J. Clin. Med. 2021, 10(2), 291; https://doi.org/10.3390/jcm10020291 - 14 Jan 2021
Cited by 37 | Viewed by 5033
Abstract
Arterial stiffness has been shown to be a subclinical marker associated with cardiovascular disease. Meanwhile, long-term exercise has been demonstrated to reduce arterial stiffness, providing a decrease in cardiovascular risk. However, the acute effect of exercise on arterial stiffness is unclear. This systematic [...] Read more.
Arterial stiffness has been shown to be a subclinical marker associated with cardiovascular disease. Meanwhile, long-term exercise has been demonstrated to reduce arterial stiffness, providing a decrease in cardiovascular risk. However, the acute effect of exercise on arterial stiffness is unclear. This systematic review and meta-analysis aimed to assess the acute effect of exercise interventions on arterial stiffness in healthy adults. We searched the Cochrane Central Register of Controlled Trials, MEDLINE (via Pubmed), Scopus, and Web of Science databases, from their inception to 30 June 2020. A meta-analysis was performed to evaluate the acute effect of exercise on arterial stiffness using random-effects models to calculate pooled effect size estimates and their corresponding 95% CI. Pulse wave velocity was measured as an arterial stiffness index. The 30 studies included in the meta-analysis showed that pulse wave velocity was not modified immediately after exercise (0 min post) (ES: 0.02; 95% CI: −0.22, 0.26), but subsequently decreased 30 min after exercise (ES: −0.27; 95% CI: −0.43, −0.12). Thereafter, pulse wave velocity increased to its initial value 24 h after exercise (ES: −0.07; 95% CI: −0.21, 0.07). Our results show that, although there is a significant reduction in pulse wave velocity 30 min after exercise, the levels of arterial stiffness return to their basal levels after 24 h. These findings could imply that, in order to achieve improvements in pulse wave velocity, exercise should be performed on a daily basis. Full article
(This article belongs to the Special Issue Peripheral Artery Disease: From Diagnosis to Treatment)
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14 pages, 3119 KiB  
Review
Infrapopliteal Artery Occlusive Disease: An Overview of Vessel Preparation and Treatment Options
by Srini Tummala, Ayush Amin and Ankit Mehta
J. Clin. Med. 2020, 9(10), 3321; https://doi.org/10.3390/jcm9103321 - 16 Oct 2020
Cited by 12 | Viewed by 3870
Abstract
Critical limb ischemia (CLI) is defined as chronic rest pain and/or the presence of tissue loss (ulcers or gangrene) in the lower extremities secondary to ischemia. CLI is a limb and potentially life-threatening disease associated with a poor prognosis with only 50% of [...] Read more.
Critical limb ischemia (CLI) is defined as chronic rest pain and/or the presence of tissue loss (ulcers or gangrene) in the lower extremities secondary to ischemia. CLI is a limb and potentially life-threatening disease associated with a poor prognosis with only 50% of patients being able to preserve both limbs within 12 months of diagnosis. CLI related to diabetes is often more extensive with multi-level long segmental arterial disease resulting in a 5–30-fold increased rate of amputation. As the incidence and prevalence of diabetes mellitus increases within our aging society, the rate of infrapopliteal artery occlusive disease (IPOD) and the need for intervention rises with it. The aim of this manuscript is to provide the reader with an overview of the various devices available for vessel preparation (VP) and treatment of IPOD in order to optimize patency rates, symptom resolution, healing of wounds, and minimize complications. Full article
(This article belongs to the Special Issue Peripheral Artery Disease: From Diagnosis to Treatment)
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