Peripheral vascular dysfunction and the aging brain.

Aging is the greatest non-modifiable risk factor for most diseases, including cardiovascular diseases (CVD), which remain the leading cause of mortality worldwide. Robust evidence indicates that CVD are a strong determinant for reduced brain health and all-cause dementia with advancing age. CVD are also closely linked with peripheral and cerebral vascular dysfunction, common contributors to the development and progression of all types of dementia, that are largely driven by excessive levels of oxidative stress (e.g., reactive oxygen species [ROS]). Emerging evidence suggests that several fundamental aging mechanisms (e.g., "hallmarks" of aging), including chronic low-grade inflammation, mitochondrial dysfunction, cellular senescence and deregulated nutrient sensing contribute to excessive ROS production and are common to both peripheral and cerebral vascular dysfunction. Therefore, targeting these mechanisms to reduce ROS-related oxidative stress and improve peripheral and/or cerebral vascular function may be a promising strategy to reduce dementia risk with aging. Investigating how certain lifestyle strategies (e.g., aerobic exercise and diet modulation) and/or select pharmacological agents (natural and synthetic) intersect with aging "hallmarks" to promote peripheral and/or cerebral vascular health represent a viable option for reducing dementia risk with aging. Therefore, the primary purpose of this review is to explore mechanistic links among peripheral vascular dysfunction, cerebral vascular dysfunction, and reduced brain health with aging. Such insight and assessments of non-invasive measures of peripheral and cerebral vascular health with aging might provide a new approach for assessing dementia risk in older adults.

Characteristics of motor evoked potentials in patients with peripheral vascular disease.

With an aging population, it is common to encounter people diagnosed with peripheral vascular disease (PVD). Some will undergo surgeries during which the spinal cord may be compromised and intraoperative neuromonitoring with motor evoked potentials (MEPs) is employed to help mitigate paralysis. No data exist on characteristics of MEPs in older, PVD patients, which would be valuable for patients undergoing spinal cord at-risk surgery or participating in neurophysiological research. Transcranial magnetic stimulation, which can be delivered to the awake patient, was used to stimulate the motor cortex of 20 patients (mean (±SD)) age 63.2yrs (±11.5) with confirmed PVD, every 10 minutes for one hour with MEPs recorded from selected upper and lower limb muscles. Data were compared to that from 20 healthy volunteers recruited for a protocol development study (28yrs (±7.6)). MEPs did not differ between patient's symptomatic and asymptomatic legs. MEP amplitudes were not different for a given muscle between patients and healthy participants. Except for vastus lateralis, disease severity did not correlate with MEP amplitude. There were no differences over time in the coefficient of variation of MEP amplitude at each time point for any muscle in patients or in healthy participants. Although latencies of MEPs were not different between patients and healthy participants for a given muscle, they were longer in older participants. The results obtained suggest PVD alone does not impact MEPs; there were no differences between more symptomatic and less symptomatic legs. Further, in general, disease severity did not corelate with MEP characteristics. With an aging population, more patients with PVD and cardiovascular risk factors will be participating in neurophysiological studies or undergoing surgery where spinal cord integrity is monitored. Our data show that MEPs from these patients can be easily evoked and interpreted.

Association of Lower Extremity Vascular Disease, Coronary Artery, and Carotid Artery Atherosclerosis in Patients with Type 2 Diabetes Mellitus.

The motive of this article is to present the case study of patients to investigate the association between the ultrasonographic findings of lower extremity vascular disease (LEAD) and plaque formation. Secondly, to examine the association between the formation of coronary artery and carotid artery atherosclerosis in patients with type 2 diabetes mellitus. 124 patients with type 2 diabetes (64 males and 60 females with the age group 25-78 years) are considered for the research studies who have registered themselves in the Department of Endocrinology and Metabolism from April 2017 to February 2019. All participants have reported their clinical information regarding diabetes, alcohol consumption, smoking status, and medication. The blood samples from subjects are collected for measurement of HbA1c, total cholesterol, triglycerides, HDL-c, and LDL-c levels. Two-dimensional ultrasound has been used to measure the inner diameter, peak flow velocity, blood flow, and spectral width of the femoral artery, pop artery, anterior iliac artery, posterior tibial artery, and dorsal artery and to calculate the artery stenosis degree. Independent factors of atherosclerosis are determined by multivariate logistic regression analysis. The results are evaluated within the control group and it is found that there is no significant impact of gender, age, and body mass index (P > 0.05) on the lower extremity vascular diseases. Those with smoking, alcohol consumption, hypertension, and dyslipidemia have higher positive rate (P < 0.05). The type 2 diabetes mellitus group has higher diastolic blood pressure and lower triglyceride (P < 0.05). Diastolic blood pressure, HbA1C, total cholesterol, HDL-c, and LDL-C are not remarkably dissimilar between the type 2 diabetes mellitus group and the control group (P > 0.05). Compared with the control group, the type 2 diabetes mellitus group has higher frequency of lower extremity vascular diseases in the dorsal artery than in the pop artery (P < 0.05). The blood flow of type 2 diabetes mellitus group is found to be lower than that of the control group, especially in the dorsal artery (P < 0.05). The blood flow velocity of the dorsal artery is accelerated (P < 0.01). Among 117 patients of type 2 diabetes mellitus (94.35%) with a certain degree of injury, there are 72 cases of type I carotid stenosis (58.06%), 30 cases of type II carotid stenosis (24.19%), and 15 cases of type III carotid stenosis (12.10%). Out of 108 subjects in the control group, there are 84 cases of type 0 carotid stenosis (77.78%), 19 cases of type I carotid stenosis (17.59%), 5 cases of type II carotid stenosis (4.63%), and 0 case of type III carotid stenosis (0.00%). Compared with the control group, carotid stenosis is more common in patients with type 2 diabetes mellitus (P < 0.05). Age, smoking, duration of diseases, systolic blood pressure, and degree of carotid stenosis are found to be associated with atherosclerosis. The findings suggest that the color Doppler ultrasonography can give early warning when applied in patients with carotid and lower extremity vascular diseases to delay the incidence of diabetic macroangiopathy and to control the development of cerebral infarction, thus providing an important basis for clinical diagnosis and treatment.

Current status of patient-reported outcome measures in vascular surgery.

A previously published review focused on generic and disease-specific patient-reported outcome measures (PROMs) relevant to vascular surgery but limited to arterial conditions. The objective of this project was to identify all available PROMs relevant to diseases treated by vascular surgeons and to evaluate vascular surgeon perceptions, barriers to widespread implementation, and concerns regarding PROMs. We provide an overview of what a PROM is and how they are developed, and summarize currently available PROMs specific to vascular surgeons. We also report results from a survey of 78 Society for Vascular Surgery members serving on committees within the Policy and Advocacy Council addressing the barriers and facilitators to using PROMs in clinical practice. Finally, we report the qualitative results of two focus groups conducted to assess granular perceptions of PROMS and preparedness of vascular surgeons for widespread implementation of PROMs. These focus groups identified a lack of awareness of existing PROMs, knowledge of how PROMs are developed and validated, and clarity around how PROMs should be used by the clinician as main subthemes for barriers to PROM implementation in clinical practice.

Ablation of lysozyme M-positive cells prevents aircraft noise-induced vascular damage without improving cerebral side effects.

Aircraft noise induces vascular and cerebral inflammation and oxidative stress causing hypertension and cardiovascular/cerebral dysfunction. With the present studies, we sought to determine the role of myeloid cells in the vascular vs. cerebral consequences of exposure to aircraft noise. Toxin-mediated ablation of lysozyme M+ (LysM+) myeloid cells was performed in LysMCreiDTR mice carrying a cre-inducible diphtheria toxin receptor. In the last 4d of toxin treatment, the animals were exposed to noise at maximum and mean sound pressure levels of 85 and 72 dB(A), respectively. Flow cytometry analysis revealed accumulation of CD45+, CD11b+, F4/80+, and Ly6G-Ly6C+ cells in the aortas of noise-exposed mice, which was prevented by LysM+ cell ablation in the periphery, whereas brain infiltrates were even exacerbated upon ablation. Aircraft noise-induced increases in blood pressure and endothelial dysfunction of the aorta and retinal/mesenteric arterioles were almost completely normalized by ablation. Correspondingly, reactive oxygen species in the aorta, heart, and retinal/mesenteric vessels were attenuated in ablated noise-exposed mice, while microglial activation and abundance in the brain was greatly increased. Expression of phagocytic NADPH oxidase (NOX-2) and vascular cell adhesion molecule-1 (VCAM-1) mRNA in the aorta was reduced, while NFκB signaling appeared to be activated in the brain upon ablation. In sum, we show dissociation of cerebral and peripheral inflammatory reactions in response to aircraft noise after LysM+ cell ablation, wherein peripheral myeloid inflammatory cells represent a dominant part of the pathomechanism for noise stress-induced cardiovascular effects and their central nervous counterparts, microglia, as key mediators in stress responses.

Clinical Outcomes of Stenting Extending Below the Inguinal Ligament for Treatment of Chronic Iliofemoral Venous Obstruction.

BACKGROUND: Patients with chronic iliofemoral venous obstructive lesions that often require stenting extending below the inguinal ligament. However, the issue of stents crossing the inguinal ligament is currently controversial. Some guidelines suggest that it should be avoided, and some guidelines suggest that in order to ensure adequate flow, the inguinal ligament can be crossed if necessary. The aim of this study was to evaluate the technical aspects and examine patency rates of stent placement across the inguinal ligament for managing iliofemoral venous obstruction. METHODS: A retrospective analysis of 127 patients with chronic iliofemoral venous obstruction were treated with interventional surgery in a single institution from January 2012 to January 2018 was conducted. All patients underwent balloon dilatation and placement of at least 2 stents extending below inguinal ligament. Inflow condition, technical success, operation duration, stent patency rates, anticoagulant selection and duration, and complications were recorded after the interventions. RESULTS: The technical success rate was 100%. No major perioperative complications occurred. The mean number of stents was 2.14 ± 0.37. Follow up periods ranged from 12 to 60 months (28.79 ± 10.90 months). Overall cumulative primary, assisted primary, and secondary stent patency rates were 81.9%, 90.5%, and 92.9% at 12 months and 70.4%, 80.9%, and 86.0% at 24 months, and 64.2%, 72.3%, and 74.3% at 36months, respectively. Cumulative patency rates at 12 months, 24 months and 36 months were significantly greater in the patients with "good" inflow as compared to "fair" inflow. The symptoms of all patients improved. None of the stents were compressed, fractured or migrated. CONCLUSIONS: Stenting across the inguinal ligament for treatment of the patients with chronic iliofemoral venous obstruction was a feasible and safe treatment with good patency and clinical results in short and midterm follow up, and stents with good inflow have better patency.

Nailfold videocapillaroscopy: a novel possible surrogate marker for the evaluation of peripheral microangiopathy in pulmonary arterial hypertension.

Nailfold videocapillaroscopy (NVC) changes in systemic sclerosis (SSc) are correlated with vascular complications, such as pulmonary arterial hypertension (PAH), supporting a potential link between peripheral and internal organ vasculopathy. The current stage of knowledge regarding NVC and PAH is discussed, focusing on the assessment of peripheral microangiopathy and a potential relationship with functional, echocardiographic, and haemodynamic markers of cardiac dysfunction. A comprehensive literature search was carried out to identify all studies focusing on NVC findings in patients with PAH, diagnosed with right heart catheterization. The majority of the studies examined NVC findings in patients with SSc-PAH, while three studies reported NVC abnormalities in patients with idiopathic PAH. Besides the pulmonary vasculature, a systemic component of microangiopathy seems to be involved in PAH. Well-designed prospective trials are warranted to validate NVC as a biomarker, with clinical implications in the diagnostic evaluation, risk stratification, and overall management of PAH in the daily clinical setting.

Bilateral Vein Compression by Popliteal Artery Aneurisms Mimicking Post-Thrombotic Syndrome.

PURPOSE: To report a case of a 79-year-old man who presented a bilateral popliteal artery aneurysm compressing both popliteal veins mimicking signs and symptoms of post-thrombotic syndrome. CASE REPORT: A 79-year-old male patient, was seen in the ambulatory clinic with a 2-year history of bilateral leg swelling, calf pain, chronic ulceration, and hyperpigmentation. Upon physical examination, lower extremities were edematous, with a 3 cm suppurative ulcer on each leg. Image studies showed a popliteal right arterial aneurysm of maximum diameter of 41.7 mm, extrinsically compressing the ipsilateral popliteal vein. Likewise, on the left leg, a popliteal arterial aneurysm of maximum diameter of 47.9 mm was encountered triggering the same phenomenon. Bilateral endovascular treatment deploying stent grafts was auspiciously performed. At 36-months follow up, his symptoms are completely resolved, and his ulcers healed. US follow up showed exclusion of the aneurysms with progressive shrinkage of both residual sacs. CONCLUSION: Popliteal artery aneurysm compressing and constraining flow in the popliteal vein must be included as a differential diagnosis among the causes of chronic venous syndromes. Prompt diagnosis with its appropriate treatment is needed for reducing severe complications caused by PAA, such as the venous disorder our patient had.

Hemodynamic and Clinical Implications of Impaired Pulmonary Vascular Reserve in the Fontan Circulation.

BACKGROUND: Pulmonary vascular disease, pulmonary endothelial dysfunction, liver fibrosis, renal disease, and exercise intolerance are common in adults with Fontan physiology. Although the pathophysiologic mechanisms linking these phenomena have been studied, certain aspects are not well understood. OBJECTIVES: This study hypothesized that impaired pulmonary vascular reserve (VR) plays a central role linking these abnormalities, and that patients with abnormal pulmonary VR with exercise, compared with patients with normal VR, would display poorer pulmonary endothelial function, greater liver stiffness, more renal dysfunction, and poorer exercise capacity. METHODS: Symptomatic adults with the Fontan palliation (n = 29) underwent invasive cardiopulmonary exercise testing, echocardiography, and assessment of microvascular function. Abnormal pulmonary VR was defined by the slope of increase in pulmonary pressure relative to cardiac output with exercise >3 mm Hg/l/min. Pulmonary endothelial function was assessed using reactive hyperemia index. End-organ function was assessed using magnetic resonance elastography-derived liver stiffness, glomerular filtration rate, N-terminal pro-B-type natriuretic peptide, and peak oxygen consumption (Vo2). RESULTS: Compared with individuals with normal VR (n = 8), those with abnormal VR (n = 21) displayed higher central and pulmonary venous pressures, and more severely impaired cardiac output and stroke volume responses to exertion, but similar pulmonary vascular resistance at rest. Patients with abnormal VR displayed more severely impaired reactive hyperemia index, increased liver stiffness, lower glomerular filtration rate, higher N-terminal pro-B-type natriuretic peptide, and lower peak Vo2. As compared to pulmonary vascular resistance at rest, slope of increase in pulmonary pressure relative to cardiac output displayed stronger correlations with reactive hyperemia index (r = -0.63 vs. r = -0.31; Meng test p = 0.009), magnetic resonance elastography-derived liver stiffness (r = 0.47 vs. r = 0.29; Meng test p = 0.07), glomerular filtration rate (r = -0.52 vs. r = -0.24; Meng test p = 0.03), N-terminal pro-B-type natriuretic peptide (r = 0.56 vs. r = 0.17; Meng test p = 0.02), and peak Vo2 (r = -0.63 vs. r = -0.26; Meng test p = 0.02). CONCLUSIONS: Pulmonary vascular limitations in Fontan physiology are related to pulmonary endothelial and end-organ dysfunction, suggesting a mechanistic link between these commonly observed findings, and these abnormalities are more apparent during exercise testing, with little relationship at rest.

A summary of data of screening of the lower limb peripheral arterial diseases in the region of Northern Hungary / Tapasztalataink az alsó végtagi perifériás artériás érbetegség szurésérol az Észak-Magyarország régióban

INTRODUCTION: The screening tool for diagnosing lower extremity arterial disease (LEAD) is the assessment of the ankle-brachial index (ABI). In patients at risk for LEAD, the purpose of screening is to avoid major adverse limb events, such as amputation. However, resting ABI can easily produce a false negative result. AIM: In light of this, our goal was to test the usefulness of an easily performed, fast and cost-effective screening method and to determine the proportion of subjects without definitive diagnoses among patients screened in general practice (with special attention to groups having negative ABI with symptoms and patients with non-compressible arteries). METHOD: 680 patients were screened from the region of Northern Hungary. We used the Edinburgh Questionnaire, recorded medical histories, major risk factors, current complaints, and medication. Physical examinations were performed, including ABI testing. RESULTS: 34% complained about lower extremity claudication; 23% had abnormal ABI values; 14% of the patients within the normal ABI range had complaints of dysbasia; 12% were in the non-compressible artery group. The ABI-negative symptomatic group's risk factor profile showed a close similarity to the clear LEAD-positive and non-compressible artery groups. CONCLUSION: The percentage of LEAD could be higher than the number of patients diagnosed by ABI screening. Nearly a quarter of the population fell into the non-compressible artery and ABI-negative symptomatic groups. When screening purposely for LEAD, these patients deserve special attention due to the insufficient selectivity and sensitivity of measurements. If there is a high clinical suspicion of LEAD in spite of normal ABI values, further assessment may be considered. Orv Hetil. 2020; 161(33): 1381-1389.

Segmental arterial mediolysis: a commonly overlooked aetiology of acute abdominal pain.

Segmental arterial mediolysis (SAM) is an uncommon condition and commonly missed diagnostic aetiology of acute abdominal pain, initially described in 1976. SAM is a non-inflammatory, non-atherosclerotic vasculopathy mostly involving the abdominal arteries with notable asymmetric involvement of the walls of the mesenteric arteries and their branches. Clinical presentation ranges from postprandial abdominal discomfort suggestive of mesenteric ischaemia to intra-abdominal bleeding. Pathophysiological explanation and prognosis of these cases are not well understood and therefore no clear guidelines for management exist. In this case report, we emphasise the imaging modalities used to reach the diagnosis and the management options available.

Midterm Outcomes of Percutaneous Deep Venous Arterialization With a Dedicated System for Patients With No-Option Chronic Limb-Threatening Ischemia: The ALPS Multicenter Study.

Purpose: To evaluate the midterm results of patients suffering from no-option chronic limb-threatening ischemia (CLTI) treated with a dedicated system for percutaneous deep venous arterialization (pDVA). Materials and Methods: Thirty-two consecutive CLTI patients (mean age 67±14 years; 20 men) treated with pDVA using the Limflow device at 4 centers between 11 July 2014 and 11 June 2018 were retrospectively analyzed. Of all patients, 21 (66%) had diabetes, 8 (25%) were on immunosuppression, 4 (16%) had dialysis-dependent renal failure, 9 (28%) had Rutherford category 6 ischemia, and 25 (78%) were deemed at high risk of amputation. The primary outcome was amputation-free survival (AFS) at 6 months. Secondary outcomes were wound healing, limb salvage, and survival at 6, 12, and 24 months. Results: Technical success was achieved in 31 patients (96.9%). The median follow-up was 34 months (range 16-63). At 6, 12, and 24 months, estimates were 83.9%, 71.0%, and 67.2% for AFS, 86.8%, 79.8% and 79.8% for limb salvage, and 36.6%, 68.2%, and 72.7% for complete wound healing, respectively. Median time to complete wound healing was 4.9 months (range 0.5-15). The DVA circuit occluded during follow-up in 21 patients; the median time to occlusion was 2.6 months. Reintervention for occlusion was performed in 17 patients: 16 because of unhealed wounds and 1 for a newly developed ulcer. Conclusion: This study represents the largest population of patients with no-option CLTI treated with pDVA using the LimFlow device with midterm results. In this complex group of patients, pDVA using the LimFlow device has been shown to be feasible, with a high technical success rate and AFS at 6 up to 24 months coupled with wound healing. In selected patients with no-option CLTI, pDVA could be a recommended treatment to prevent amputation and heal wounds.

Effects of modified Wenjing decoction on microcirculation in reproductive organs in rats with symptom patterns of cold coagulation and blood stasis.

OBJECTIVE: To investigate the relationship between symptom patterns of cold coagulation and blood stasis (CCBS) and microcirculation disturbance. In addition, we determined the efficacy of modified Wenjing decoction (WJD) for the treatment of CCBS. METHODS: CCBS was induced in rats with an ice-water bath treatment. The ovarian function, microvascular and circulatory status of reproductive organs, and function of local microvascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) were evaluated. RESULTS: Ovarian dysfunction was observed in the rats with CCBS. It was characterized by the presence of an estrous cycle disorder and a decrease in reproductive hormone levels. Microvascular circulation disorders were associated with an imbalance in vasoconstriction, relaxation substances, nitric oxide, abnormal blood flow in whole blood, and decreased blood flow in the auricle and uterus. VECs were damaged, and VSMCs contracted and proliferated in ovarian and uterine tissues. CONCLUSION: Our findings suggest that the dysfunctional reproductive organs observed in gynecological CCBS may be closely related to the microcirculation disturbance of local tissues, microvascular contraction, and vascular remodeling. Modified WJD can be used to treat CCBS by improving microcirculation in reproductive organs.

Experience of a 40-day (6 week) LMWH treatment for isolated distal deep vein thrombosis.

Clinical significance of distal deep vein thrombosis (DVT) is important as it can potentially result in pulmonary embolism (PE), DVT extension, DVT recurrence and post-thrombotic syndrome (PTS). Controversy remains about the necessity and modalities of anticoagulation in all distal DVT. Evaluation of the efficiency of a 40-day weight-based low molecular weight heparin (LMWH) treatment in a cohort of 119 consecutive patients with distal DVT. Compression ultrasonography of the lower limb was performed initially for diagnosis as well as at the end of the treatment to identify persistence or resolution of the blood clot. A 3-month follow-up estimated the rates of PE, DVT recurrence, DVT extension, PTS and bleeding. Risk factors for DVT were considered to evaluate a possible correlation between them and the outcomes. In 71.4% of the patients the blood clot was totally dissolved and thrombus persistence was statistically associated with the number of initially involved veins. DVT recurrence occurred in 5% of patients and was also associated with the number of initial clotted veins. DVT extension and PTS rates were present in 1.7% and 3.4% respectively and no patient was diagnosed with PE or bleeding. This retrospective study including a limited number of patients and no control group supports that a 40-day weight-based LMWH treatment after distal DVT seems to be efficient when one single vein is initially affected whereas for multiple vein distal DVT and to avoid potential DVT recurrence, longer than 6 weeks of anticoagulant treatment is required. Our results support safety of the treatment, its potential to prevent DVT extension and the occurrence of PE.

Inferior Pancreatico-Duodenal Artery Aneurysm with Superior Mesenteric Artery Stenosis.

Pancreatico-duodenal artery aneurysm (PDAA) associated with stenosis or occlusion of the celiac trunk is a rare condition. Furthermore, PDAAs associated with stenosis of the superior mesenteric artery (SMA) are even more uncommon, with only six cases reported in the literature. We report a case of a 61-year old male patient who presented with hematemesis, haematochezia and haemorrhagic shock. The upper gastrointestinal endoscopy revealed an ulcerous lesion at the third portion of the duodenum, without achieving the haemostasis. The emergency laparotomy (suture of the lesion and gastro-entero-anastomosis) permitted temporary haemostasis. Computed tomography angiography identified the PDAA ruptured into the third portion of the duodenum and the SMA stenosis at its origin; a dense network of collateral vessels was present. The patient was successfully managed with coil embolization. Short and mid-term follow-up were without incidents.

Modified Pull-Through Technique for Cardiac Resynchronization Therapy Upgrades in Patients with Occluded Access Veins.

The number of procedures for upgrading implantable devices for cardiac resynchronization therapy has increased considerably during the last decade. A major challenge that operators face in these circumstances is occlusion of the access vein. We have modified a pull-through method to overcome this obstacle. Six consecutive patients with occluded access veins and well-developed collateral networks underwent a procedure in which the occluded vein was recanalized by snaring the existing atrial lead via transfemoral access. Upgrading the device was successful in all patients; none had intraprocedural complications. Our experience shows that our modified pull-through technique may be a feasible alternative for upgrading cardiac resynchronization therapy in patients with venous occlusion.

A conservative approach to select patients with ischemic wounds is safe and effective in the setting of deferred revascularization.

OBJECTIVE: The Wound, Ischemia, and foot Infection classification system has been validated to predict benefit from inmediate revascularization and major amputation risk among patients with peripheral arterial disease. Our primary goal was to evaluate wound healing, limb salvage, and survival among patients with ischemic wounds undergoing revascularization when intervention was deferred by a trial of conservative wound therapy. METHODS: All patients with peripheral arterial disease and tissue loss are prospectively enrolled into our Prevention of Amputation in Veterans Everywhere limb preservation program. Limbs are stratified into a validated pathway of care based on predetermined criteria (immediate revascularization, conservative treatment, primary amputation, and palliative care). Limbs allocated to the conservative strategy that failed to demonstrate adequate wound healing and were candidates, underwent deferred revascularization. Rates of wound healing, freedom from major amputation, and survival were compared between patients who underwent deferred revascularization with those who received immediate revascularization by univariate and multivariate analysis. RESULTS: Between January 2008 and December 2017, 855 limbs were prospectively enrolled into the Prevention of Amputation in Veterans Everywhere program. A total of 203 limbs underwent immediate revascularization. Of 236 limbs stratified to a conservative approach, 185 (78.4%) healed and 33 (14.0%) underwent deferred revascularization (mean, 2.7 ± 2.6 months). The mean long-term follow-up was 51.7 ± 37.0 months. Deferred compared with immediate revascularization demonstrated similar rates of wound healing (66.7% vs 57.6%; P = .33), freedom from major amputation (81.8% vs 74.9%; P = .39), and survival (54.5% vs 50.7%; P = .69). After adjustment for overall Wound, Ischemia, and foot Infection stratification stages, deferred revascularization remained similar to immediate revascularization for wound healing (hazard ratio [HR], 1.5; 95% confidence interval [CI], 0.7-3.2), freedom from major amputation (HR, 0.7; 95% CI, 0.3-1.7) and survival (HR, 1.2; 95% CI, 0.6-2.4). CONCLUSIONS: Limbs with mild to moderate ischemia that fail a trial of conservative wound therapy and undergo deferred revascularization achieve similar rates of wound healing, limb salvage, and survival compared with limbs undergoing immediate revascularization. A stratified approach to critical limb ischemia is safe and can avoid unnecessary procedures in selected patients.