Pharmacotherapy and revascularization strategies of peripheral artery disease.

The global epidemiological transition of atherosclerotic vascular diseases is witnessing a rapid redistribution of its burden, shifting from high-income to low- and middle-income countries. With a wide clinical spectrum, spanning from intermittent claudication to more complex critical limb threatening ischemia, nonhealing ulcers, gangrene as well as acute limb ischemia, peripheral artery disease is often faced with the challenges of under-diagnosis and under-treatment despite its high prevalence. The management of peripheral arterial disease in patients with multiple comorbidities presents a formidable challenge and remains a pressing global health concern. In this review, we aim to provide an in-depth overview of the pathophysiology of peripheral artery disease and explore evidence-based management strategies encompassing pharmacological, lifestyle, interventional, and surgical approaches. By addressing these challenges, the review contributes to a better understanding of the evolving landscape of peripheral artery disease, offering insights into effective and holistic management strategies.

Feasibility study of Syngo iFlow in predicting hemodynamic improvement post-endovascular procedure in peripheral artery disease.

OBJECTIVE: This study endeavors to examine the feasibility of predicting the clinical outcomes of patients suffering from peripheral artery disease (PAD) who undergo endovascular intervention, by employing the Syngo iFlow technology. METHODS: Retrospectively enrolling 76 patients from December 2021 to May 2023, yielding a total of 77 affected limbs, this study employs clinical outcomes (improvement or otherwise) as the gold standard. Two physicians conducted visual assessments on both DSA and iFlow images to gauge patient improvement and assessed inter-observer consistency for each image modality. The Time to Peak (TTP) of regions of interest (ROI) at the femoral head, knee joint, and ankle joint was measured. Differences in pre- and post-procedure TTP were juxtaposed, and statistically significant parameter cutoff values were identified via ROC analysis. Employing these cutoffs for TTP classification, multivariate logistic regression and the C-statistic were utilized to assess the predictive value of distinct parameters for clinical success. RESULTS: Endovascular procedure exhibited technical and clinical success rates of 82.58 and 75.32%, respectively. Diagnostic performance of iFlow image visual assessment surpassed that of DSA images. Inter-observer agreement for iFlow and DSA image evaluations was equivalent (κ = 0.48 vs 0.50). Post-classification using cutoff values, multivariate logistic regression demonstrated the statistical significance of ankle joint TTP in post-procedure iFlow images of the endovascular procedure for clinical success evaluation (OR 7.21; 95% CI 1.68, 35.21; P = 0.010), with a C-statistic of 0.612. CONCLUSION: Syngo iFlow color-encoded imagery holds practical value in assessing the technical success of post-endovascular procedures, offering comprehensive lower limb arterial perfusion visualization. Its quantifiable parameters exhibit promising potential for prognosticating clinical success.

Effectiveness of Repetitive Hyperbaric Oxygen Therapy for Chronic Limb-Threatening Ischemia.

BACKGROUND: Lower extremity artery disease is strongly associated with morbidity and is typically addressed through revascularization interventions. We assessed the clinical outcomes of patients with chronic limb-threatening ischemia (CLTI) without revascularization who did and did not undergo repetitive hyperbaric oxygen therapy (HBOT). METHODS: Between April 2002 and March 2017, the records of 58 patients with CLTI (Rutherford classification 4 in 19% and 5 in 81%) were evaluated retrospectively. HBOT was performed at 2.8 atm of oxygen (HBOT group). The control group included those who could not continue HBOT and historical controls. Patients in poor general health or with an indication for revascularization therapy were excluded. We examined major adverse events (MAEs) and limb salvage rates. Independent predictors and risk stratification were analyzed using a multivariate regression analysis. RESULTS: The mean age was 71±13 years. Of all patients, 67% had diabetes and 43% were undergoing hemodialysis. The mean follow-up period was 4.3±0.8 years. The overall survival rate was 84.5% and 81.0% at 1 and 3 years, respectively. The Cox regression analysis indicated that high body mass index (odds ratio [OR]: 0.86; 95% confidence interval [CI]: 0.76-0.97; p=0.01), well-nourished (OR: 1.21; 95% CI: 1.01-1.45), and HBOT (OR: 0.05; 95% CI: 0.01-0.26; p<0.001) independently predicted absence of MAEs. For major limb amputation, the ankle-brachial index (OR: 0.2; 95% CI: 0.05-0.86; p=0.03) and HBOT (OR: 0.04; 95% CI: 0.004-0.32; p=0.003) were independent predictors. CONCLUSIONS: Repetitive, stand-alone HBOT was associated with MAE-free survival and limb salvage in patients with CLTI.

Socioeconomic factors predict successful supervised exercise therapy completion.

OBJECTIVE: Supervised exercise therapy (SET) for patients with intermittent claudication (IC) can lower the risk of progression to chronic limb-threatening ischemia and amputation, while preserving and restoring functional status. Despite supporting evidence, it remains underutilized, and among those who initiate programs, attrition rates are extremely high. We hypothesize that socioeconomic factors may represent significant barriers to SET completion. METHODS: Patients with IC referred to SET at a multi-hospital, single-institution health care system (2018-2022) from a prospectively maintained database were retrospectively analyzed. Our primary endpoint was SET program completion and graduation, defined as completion of 36 sessions. Our secondary endpoints were vascular intervention within 1 year of referral and change in ankle-brachial index (ABI). Baseline demographics were assessed using standard statistical methods. Predictors of SET graduation were analyzed using multivariable logistic regression generating adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Change in ABI was analyzed using t-test between subgroups. Reasons for attrition were tabulated. Patient Health Questionnaire-9 (PHQ-9), metabolic equivalent level, Vascular QOL, Duke Activity Status, and ABI were analyzed using paired t-tests across the entire cohort. RESULTS: Fifty-two patients met inclusion criteria: mean age 67.85 ± 10.69 years, 19 females (36.54%), mean baseline ABI of 0.77 ± 0.16. The co-pays for 100% of patients were fully covered by primary and secondary insurance plans. Twenty-one patients (40.38%) completed SET. On multivariable analysis, residence in a ZIP code with median household income <$47,000 (aOR, 0.10; 95% CI, 0.01-0.76; P = .03) and higher body mass index (aOR, 0.81; 95% CI, 0.67-0.99; P = .04) were significant barriers to SET graduation. There were no differences in ABI change or vascular intervention within 1 year between graduates and non-graduates. Non-graduates reported transportation challenges (25.00%), lack of motivation (20.83%), and illness/functional limitation (20.83%) as primary reasons for SET attrition. Metabolic Equivalent Level (P ≤ .01) and Duke Activity Status scores (P = .04) were significantly greater after participating in a SET program. CONCLUSIONS: Although SET participation improves lower extremity and functionality outcomes, only 40% of referred patients completed therapy in our cohort. Our findings suggest that both socioeconomic and functional factors influence the odds of completing SET programs, indicating a need for holistic pre-referral assessment to facilitate enhanced program accessibility for these populations.

Low-intensity resistance exercise with blood flow restriction for patients with claudication: A randomized controlled feasibility trial.

BACKGROUND: Claudication is a common and debilitating symptom of peripheral artery disease, resulting in poor exercise performance and quality of life (QoL). Supervised exercise programs are an effective rehabilitation for patients with claudication, but they are poorly adhered to, in part due to the high pain and effort associated with walking, aerobic, and resistance exercise. Low-intensity resistance exercise with blood flow restriction (BFR) represents an alternative exercise method for individuals who are intolerant to high-intensity protocols. The aim of this study was to evaluate the feasibility of a supervised BFR program in patients with claudication. METHODS: Thirty patients with stable claudication completed an 8-week supervised exercise program and were randomized to either BFR (n = 15) or a control of matched exercise without BFR (control; n = 15). Feasibility, safety, and efficacy were assessed. RESULTS: All success criteria of the feasibility trial were met. Exercise adherence was high (BFR = 78.3%, control = 83.8%), loss to follow up was 10%, and there were no adverse events. Clinical improvement in walking was achieved in 86% of patients in the BFR group but in only 46% of patients in the control group. Time to claudication pain during walking increased by 35% for BFR but was unchanged for the control. QoL for the BFR group showed improved mobility, ability to do usual activities, pain, depression, and overall health at follow up. CONCLUSION: A supervised blood flow restriction program is feasible in patients with claudication and has the potential to increase exercise performance, reduce pain, and improve QoL. (Clinicaltrials.gov Identifier: NCT04890275).

A comparison of the perceptions of wearing an ankle foot orthosis by individuals with peripheral artery disease according to their baseline-level of physical activity.

INTRODUCTION: Peripheral artery disease (PAD) is a prevalent cardiovascular disease that limits an individual's ability to walk. One potential way to improve physical activity for patients with PAD is an ankle foot orthosis (AFO). Previous research has found that various factors may influence an individual's willingness to wear AFOs. However, one factor that has been understudied is an individual's baseline physical activity level prior to wearing AFOs. Therefore, the purpose of this study was to compare the perceptions of wearing AFOs for 3 months among individuals with PAD according to their baseline level of physical activity. METHODS: Accelerometer-derived physical activity prior to AFO prescription was used to classify participants into either a higher or lower activity group. Semi-structured interviews were conducted at 1.5 and 3-months after wearing the AFOs to assess participants' perceptions of using the orthosis. Data were analyzed by a directed content analysis approach, then the percentage of respondents for each theme were calculated and compared between higher and lower activity groups. FINDINGS: Several differences were found. Participants in the higher activity group more often reported positive impacts from wearing the AFOs. Additionally, participants who were in the lower activity group more often reported the AFOs caused physical pain while participants in the higher activity group more often reported the device was uncomfortable during daily activities. CONCLUSION: Baseline physical activity levels may help to better understand barriers to wear and needed support to increase adherence to an AFO wear prescription, especially for patients with PAD with limited activity.

Risk Factor Analysis for Crossing Failure in Primary Antegrade Wire-Catheter Approach for Femoropopliteal Chronic Total Occlusions.

INTRODUCTION: Antegrade wire-catheter crossing remains the primary approach for femoropopliteal interventions. Nonetheless, data reporting on crossing failure are limited. Aim of this study is to identify risk factors for antegrade crossing failure in patients with femoropopliteal chronic total occlusions (CTOs). METHODS: This is a single-center, retrospective analysis. Patients with femoropopliteal CTOs treated between May 2018 and February 2020 were included into this study. Primary endpoint of this analysis was primary crossing success defined as successful antegrade crossing without the use of retrograde access, crossing or re-entry devices. The assisted crossing success was additionally analyzed. A logistic regression analysis identified risk factors for failed primary antegrade crossing. RESULTS: Data from 300 patients were analyzed. The majority (n=183, 61%) presented with lifestyle limiting claudication. The mean lesion length was 180 mm [interquartile range (IQR) 100-260 mm], whereas the median CTO length was 100 mm (IQR=50-210 mm). A chronic total occlusion crossing approach based on plaque morphology (CTOP) type I configuration was observed in 9% (n=26) of the lesions, type II in 61% (n=183), type III in 8% (n=25), and type IV in 66 CTOs (n= 66, 22%). Severe calcification based on the Peripheral Arterial Calcium Scoring Scale (PACSS), Peripheral Academic Research Consortium (PARC), and 360° grading systems was identified in 17%, 24%, and 28% of the lesions, respectively. A contralateral femoral access was used in 278 cases (93%). The primary crossing success amounted to 70% (n=210). The use of a re-entry device in 28 patients (9%) or of a combined antegrade-retrograde approach in 11% (n=34) of the cases increased the assisted crossing success to 89% (n=267). The presence of calcification (odds ratio [OR]=4.2, 95% CI=1.7-10.2) or of circumferential calcium (OR=2.5, 95% CI=1.3-4.9), a CTOP class ΙΙΙ or ΙV (OR=1.9, 95% CI=1.4-2.6), a proximal superficial femoral artery (SFA) occlusion (OR=3.5, 95% CI=1.7-7.4) and a CTO at P3 (OR=4.1, 95% CI=1.5-10.8) were associated with an increased risk for antegrade crossing failure. CONCLUSIONS: In this study, chronic total occlusions (CTO) morphology, calcification burden, and lesion's location were identified as independent risk factors for failed antegrade crossing. Nonetheless, the use of alternative crossing strategies significantly increased the overall crossing success.

The Impact of Controlled Physical Training with Hydrotherapy on Changes in Swelling and Claudication Distance in Patients with Atherosclerotic Ischemia of the Lower Limbs.

BACKGROUND: Patients with peripheral artery disease (PAD) often experience intermittent claudication. It is manifested by pain typically seen in the distal part of the legs during walking, which impairs the ability to walk, limits physical activity and results in lower health-related quality of life. It often leads to chronic ischemic pain, ulceration and even amputation. The aim of the study was to evaluate the effect of controlled physical training and whirlpool massage on changes in circuits, range of motion and distance of claudication in people with atherosclerotic ischemia of the lower limbs. MATERIAL AND METHODS: The study included 100 patients, males and females aged 39 to 79 years, with peripheral circulation disorders of the lower limbs. The subjects were randomly divided into two groups. Group I (G) was treated with a series of 10 lower-limb whirling massages and took part in individually planned training, including breathing, relaxation and active free lower-limb exercises. Group II-control group (GC) took part only in individually planned training. Prior to the treatment procedures and after their completion, the ranges of movement of the ankle joint and the circumference of the lower limbs were measured and the corridor test (6MWT, six-minute walk test) was performed. RESULTS: Statistically significant reduction in the circumference of the foot, ankle, calf and thigh in the G group was noticed. Both, in G and in GC group, a statistically significant increase in the range of dorsiflexion of the foot was found in comparison to the period before the procedures (p = 0.010; p = 0.006, respectively). There was also a statistically significant increase in the range of motion of the plantar flexion of the foot after the procedures in G (p = 0.007) and in GC (p = 0.048). Differences in the circumference of the lower limbs and the range of ankle joint movements between the study group and the control group before and after the therapy were not statistically significant. However, there was a statistically significant difference between these groups after the procedures in the 6-min walk test-significantly higher values of 6MWT were recorded in group G (p = 0.003). CONCLUSIONS: Individually planned training, supplemented with hydrotherapy as thermal therapy, has a beneficial effect on reducing swelling of the lower limbs, increasing the range of foot movements and extending the distance in the 6-min walk test.

Sirolimus-Coated Balloon Angioplasty of Infra-popliteal Lesions for the Treatment of Chronic Limb-Threatening Ischemia: Study Protocol for the Randomized Controlled LIMES Study.

PURPOSE: Evidence on efficacy and long-term safety of paclitaxel-coated devices is still conflicting. Therefore, this study aims to assess whether sirolimus-coated balloon angioplasty is safe and effective for the treatment of infra-popliteal occlusions in patients with chronic limb-threatening ischemia (CLTI). STUDY DESIGN: The randomized controlled, single-blinded, multicentre, investigator-initiated study aims to enrol 230 participants with CLTI and infra-popliteal occlusions at up to 25 centres. Patients will be randomized in a 1:1 ratio to either sirolimus-coated balloon angioplasty or to plain old balloon angioplasty (POBA). Bailout stenting in case of flow-limiting dissection or ≥ 50% residual diameter stenosis is permitted. OUTCOME MEASURES: Primary outcome is the Kaplan-Meier estimate of primary patency at 6 months, defined as the absence of target lesion occlusion with restoration of in-line flow to the ankle. Key secondary outcome is non-inferiority in the proportionate occurrence of major adverse limb events and perioperative all-cause death at 30 days. Overall, participants will be followed for 36 months to assess further secondary efficacy and safety outcomes. ASSUMED GAIN OF KNOWLEDGE: If sirolimus-coated balloon angioplasty turns out to be superior to uncoated-balloon angioplasty regarding patency of infra-popliteal lesions without safety signals, it could become a welcome treatment option for patients with CLTI. Trial Registration ClinicalTrial.gov Identifier: NCT04772300, German Clinical Trials Register: DRKS00024629. Level of Evidence Level 2a, randomized controlled trial.

Limb Salvage with Multiple Modalities: A Case Report of a Diabetic Heel Ulcer Associated with Peripheral Arterial Disease.

ABSTRACT: A large diabetic heel ulcer with peripheral arterial disease is an independent predictor of limb loss; below-knee amputation is not uncommon in such cases. One treatment is multimodal therapy, which includes partial calcanectomy. Because there is a limit to the ulcer surface area that can be sutured after partial calcanectomy, the remaining raw surface is treated with another method. In this case report, the authors describe a patient with peripheral arterial disease who had a 7 × 9-cm diabetic heel ulcer. The patient was treated with partial calcanectomy after catheter-based endovascular therapy revascularization and then maggot therapy after residual-wound dimensions were reduced by negative-pressure wound therapy.

Effects of home-based leg heat therapy on walking performance in patients with symptomatic peripheral artery disease: a pilot randomized trial.

Few noninvasive therapies currently exist to improve functional capacity in people with lower extremity peripheral artery disease (PAD). The goal of the present study was to test the hypothesis that unsupervised, home-based leg heat therapy (HT) using water-circulating trousers perfused with warm water would improve walking performance in patients with PAD. Patients with symptomatic PAD were randomized into either leg HT (n = 18) or a sham treatment (n = 16). Patients were provided with water-circulating trousers and a portable pump and were asked to apply the therapy daily (7 days/wk, 90 min/session) for 8 wk. The primary study outcome was the change from baseline in 6-min walk distance at 8-wk follow-up. Secondary outcomes included the claudication onset-time, peak walking time, peak pulmonary oxygen consumption and peak blood pressure during a graded treadmill test, resting blood pressure, the ankle-brachial index, postocclusive reactive hyperemia in the calf, cutaneous microvascular reactivity, and perceived quality of life. Of the 34 participants randomized, 29 completed the 8-wk follow-up. The change in 6-min walk distance at the 8-wk follow-up was significantly higher (P = 0.029) in the group exposed to HT than in the sham-treated group (Sham: median: -0.9; 25%, 75% percentiles: -5.8, 14.3; HT: median: 21.3; 25%, 75% percentiles: 10.1, 42.4, P = 0.029). There were no significant differences in secondary outcomes between the HT and sham group at 8-wk follow-up. The results of this pilot study indicate that unsupervised, home-based leg HT is safe, well-tolerated, and elicits a clinically meaningful improvement in walking tolerance in patients with symptomatic PAD.NEW & NOTEWORTHY This is the first sham-controlled trial to examine the effects of home-based leg heat therapy (HT) on walking performance in patients with peripheral artery disease (PAD). We demonstrate that unsupervised HT using water-circulating trousers is safe, well-tolerated, and elicits meaningful changes in walking ability in patients with symptomatic PAD. This home-based treatment option is practical, painless, and may be a feasible adjunctive therapy to counteract the decline in lower extremity physical function in patients with PAD.

Treatment of end-stage peripheral artery disease by neuromodulation.

BACKGROUND: Neuromodulation is a therapeutic option to improve limb salvage in end-stage peripheral arterial disease (PAD), but there is no consensus on its indication for spinal cord stimulation (SCS) in PAD patients. OBJECTIVE: The aim of this study was to present the outcome of end-stage PAD patients treated with SCS. METHODS: This study is a retrospective analysis based on a local prospective registry. Neuromodulation was performed if there was: 1) no revascularisation option, 2) no septicemia, 3) and Rutherford stage 4-6. The primary endpoint of the study was limb salvage. Secondary endpoints were reduction in pain or simply pain reduction pain (assessed using a visual anlog scale/VAS) and improvement in walking distance. RESULTS: Limb salvage was reached in 30/34 patients (88%). Patients reported a significant reduction in pain on the 10-point VAS scale from baseline (median = 7.5, IQR = 7-8) to follow-up at 2 years (median = 0, IQR 0-2.75), p < 0.001. Walking distance also improved from preoperative (median = 50 m, IQR = 20-50 m) to follow-up at 2 years (median = 150 m, IQR 50-272 m), p < 0.001. RESULTS: SCS implantation in patients with end-stage PAD can enable limb salvage in a high percentage of cases and increase mobility due to pain reduction. The role of microcirculation in these improvements needs to be investigated in further studies.

Twelve-Month Clinical Outcomes of Percutaneous Deep Venous Arterialization with Alternative Techniques and Ordinary Endovascular Therapy Devices for Patients with Chronic Limb-Threatening Ischemia: Results of the DEPARTURE Japan Study.

PURPOSE: A dedicated treatment strategy is not yet established for patients with no-option chronic limb-threatening ischemia. This study aimed to evaluate the clinical outcomes of percutaneous deep venous arterialization in Japanese patients with no-option chronic limb-threatening ischemia. MATERIALS AND METHODS: Data of 18 consecutive patients with chronic limb-threatening ischemia (18 limbs; mean age: 75.5 ± 8.5 years; 14 men) who underwent percutaneous deep venous arterialization between January 2016 and November 2020 were retrospectively reviewed. The limb salvage, amputation-free survival, and wound healing rates were evaluated using the Kaplan-Meier method. RESULTS: Among 18 patients, 14 (77.8%) had diabetes, 6 (33.3%) had a non-ambulatory status, 16 (88.9%) received hemodialysis, and 15 (83.3%) had wound, ischemia, and foot infection of clinical stage 4. Rutherford 5 was observed in 33.7% of the patients and Rutherford 6 in 66.7%. The technical success rate of percutaneous deep venous arterialization was 88.9%. Four patients required major amputation within 30 days; percutaneous deep venous arterialization failed in two of these patients. At 6 and 12 months, the limb salvage rates, amputation-free survival rates, and complete wound healing rates were 72.2 and 72.2%, 55.6 and 49.4%, and 23.0 and 53.2%, respectively. The median time to complete wound healing was 234 (interquartile range, 127-306) days. CONCLUSION: This study presented the clinical outcomes of patients with chronic limb-threatening ischemia who underwent percutaneous deep venous arterialization in Japan. Acceptable, safe, and efficacious results were reported. Before major amputation, percutaneous deep venous arterialization can be considered for patients with no-option chronic limb-threatening ischemia. LEVEL OF EVIDENCE: Level 3. Non-randomized, follow-up study.

Electromagnetic energy (670 nm) stimulates vasodilation through activation of the large conductance potassium channel (BKCa).

INTRODUCTION: Peripheral artery disease (PAD) is a highly morbid condition in which impaired blood flow to the limbs leads to pain and tissue loss. Previously we identified 670 nm electromagnetic energy (R/NIR) to increase nitric oxide levels in cells and tissue. NO elicits relaxation of smooth muscle (SMC) by stimulating potassium efflux and membrane hyperpolarization. The actions of energy on ion channel activity have yet to be explored. Here we hypothesized R/NIR stimulates vasodilation through activation of potassium channels in SMC. METHODS: Femoral arteries or facial arteries from C57Bl/6 and Slo1-/- mice were isolated, pressurized to 60 mmHg, pre-constricted with U46619, and irradiated twice with energy R/NIR (10 mW/cm2 for 5 min) with a 10 min dark period between irradiations. Single-channel K+ currents were recorded at room temperature from cell-attached and excised inside-out membrane patches of freshly isolated mouse femoral arterial muscle cells using the patch-clamp technique. RESULTS: R/NIR stimulated vasodilation requires functional activation of the large conductance potassium channels. There is a voltage dependent outward current in SMC with light stimulation, which is due to increases in the open state probability of channel opening. R/NIR modulation of channel opening is eliminated pharmacologically (paxilline) and genetically (BKca α subunit knockout). There is no direct action of light to modulate channel activity as excised patches did not increase the open state probability of channel opening. CONCLUSION: R/NIR vasodilation requires indirect activation of the BKca channel.

Head-to-head comparison of sirolimus- versus paclitaxel-coated balloon angioplasty in the femoropopliteal artery: study protocol for the randomized controlled SIRONA trial.

BACKGROUND: Endovascular revascularization has established as the first-line therapy of femoropopliteal artery disease. Paclitaxel-coated balloon angioplasty proved to be superior to plain old balloon angioplasty (POBA) regarding prevention of restenosis and need for recurrent revascularization. Over the past years, paclitaxel was the only active drug to inhibit neointimal proliferation which could be processed to an appropriate balloon coating. The purpose of this study is to assess whether efficacy and safety of sirolimus-coated balloon angioplasty is noninferior to paclitaxel-coated balloon angioplasty. METHODS: This randomized controlled, single-blinded, multicentre, investigator-initiated noninferiority trial aims to enrol a total of 478 participants with symptomatic femoropopliteal artery disease of Rutherford category 2 to 4 due to de novo stenosis or restenosis. After pre-dilation, participants will be allocated in a 1:1 ratio to either sirolimus- or paclitaxel-coated balloon angioplasty. Post-dilation with the drug-coated balloon (DCB) used or standard balloon is mandatory in case ≥ 50%, and optional in case of ≥ 30% residual diameter stenosis. Bailout stenting with bare-metal nitinol stents should be conducted in case of flow-limiting dissection. Primary noninferiority endpoints are primary patency and the composite of all-cause mortality, major target limb amputation, and clinically driven target lesion revascularization at 12 months. Secondary outcomes are clinical and hemodynamic improvement, change in health-related quality of life, and safety throughout 60 months. DISCUSSION: Although concerns about long-term safety of paclitaxel-coated devices were not confirmed by recent patient-level data analyses, conflicting evidence contributed to a loss of confidence among patients and physicians. Therefore, sirolimus, known for a broader therapeutic range than paclitaxel, may serve as a welcome alternative. This will be justified if noninferiority of sirolimus-coated balloon angioplasty against the current standard of paclitaxel-coated balloon angioplasty can be demonstrated. TRIAL REGISTRATION: ClinicalTrials.gov NCT04475783 . Registered on 17 July 2020 EUDAMED No. CIV-20-11-035172, DRKS00022452.

Hyperbaric oxygen therapy and fluorescence angiography in arterial insufficiency secondary to injection of crushed hydromorphone.

INTRODUCTION: Foreign body emboli can lead to acute arterial insufficiency. We present a case report of upper extremity arterial insufficiency in an intravenous (IV) drug user secondary to intra-arterial injection of crushed tablet particles successfully treated with hyperbaric oxygen (HBO2) therapy. CASE: A 37-year-old right-hand-dominant male developed pain and swelling of the left hand after attempting to inject crushed hydromorphone tablets into his venous circulation. Angiography revealed incomplete distal filling of the proper digital arteries, princeps pollicis, and radialis indicis branches of the left hand. The patient was treated with HBO2 for acute arterial insufficiency, secondary to these findings. Fluorescence angiography was performed prior to, during and after completion of HBO2, which showed improved perfusion of the hand upon completion of serial imaging. The patient underwent subsequent partial amputation of the left second digit and removal of the thenar and third finger pads. DISCUSSION: Much of the literature on treatment of arterial insufficiency with HBO2 are in relation to chronic problem wounds. However, there is limited data on adjunctive treatment with HBO2 for foreign body embolism. Fluorescence angiography and clinical exam were used to track tissue perfusion and progression throughout course of therapy with HBO2. CONCLUSION: Acute arterial insufficiency induced by foreign body embolism was successfully treated with HBO2 and provided increased tissue salvage of the patient's hand. The use of fluorescence angiography as a secondary measure of perfusion can provide additional insight regarding qualitative tissue oxygenation and may be a viable tool to track patient progress during HBO2 treatment.

Phytochemicals as Therapeutic Interventions in Peripheral Artery Disease.

Peripheral artery disease (PAD) affects over 200 million people worldwide, resulting in significant morbidity and mortality, yet treatment options remain limited. Among the manifestations of PAD is a severe functional disability and decline, which is thought to be the result of different pathophysiological mechanisms including oxidative stress, skeletal muscle pathology, and reduced nitric oxide bioavailability. Thus, compounds that target these mechanisms may have a therapeutic effect on walking performance in PAD patients. Phytochemicals produced by plants have been widely studied for their potential health effects and role in various diseases including cardiovascular disease and cancer. In this review, we focus on PAD and discuss the evidence related to the clinical utility of different phytochemicals. We discuss phytochemical research in preclinical models of PAD, and we highlight the results of the available clinical trials that have assessed the effects of these compounds on PAD patient functional outcomes.

Patients with Diabetes Complicated by Peripheral Artery Disease: the Current State of Knowledge on Physiotherapy Interventions.

Diabetes mellitus (DM) is one of the major public health problems that account for morbidity, mortality, and disability worldwide. The presence of DM increases the risk of peripheral artery disease (PAD), as well as accelerates its course, making these patients more susceptible to ischemic events and impaired functional status. Unfortunately, alternative treatments for vascular complications in diabetes are poorly researched. Physiotherapy (kinesitherapy combined with different physical therapy agents) in individuals with DM and coexisting PAD may offer an important complementary therapy alternative. Early therapeutic measures can significantly improve patient outcomes, reduce cardiovascular risk, and improve daily life quality. The article provides an update on the current state of knowledge on physiotherapy interventions in the course of DM in patients with coexisting PAD.

Microvascular Dysfunction in Peripheral Artery Disease: Is Heat Therapy a Viable Treatment?

Peripheral artery disease (PAD) is characterized by the development of atherosclerotic plaques in the lower-body conduit arteries. PAD is commonly accompanied by microvascular disease, which may result in poor wound healing, plantar ulcer development, and subsequent limb amputation. Understanding the mechanisms underlying the development of plantar ulcers is a critical step in the development of adequate treatment options for patients with PAD. Skin is classified into two major components: glabrous and non-glabrous. These skin types have unique microcirculation characteristics, making it important to differentiate between the two when investigating mechanisms for plantar ulcer development in PAD. There is evidence for a microcirculation compensatory mechanism in PAD. This is evident by the maintenance of basal microcirculation perfusion and capillary filling pressure despite a reduced pressure differential beyond an occlusion in non-critical limb ischemia PAD. The major mechanism for this compensatory system seems to be progressive vasodilation of the arterial network below an occlusion. Recently, heat therapies have emerged as novel treatment options for attenuating the progression of PAD. Heat therapies are capable of stimulating the cardiovascular system, which may lead to beneficial adaptations that may ultimately reduce fatigue during walking in PAD. Early work in this area has shown that full-body heating is capable of generating an acute cardiovascular response, similar to exercise, which has been suggested as the most efficient treatment modality and may generate adaptations with chronic exposure. Heat therapies may emerge as a conservative treatment option capable of attenuating the progression of PAD and ultimately impeding the development of plantar ulcers.