Effects of additional exercise therapy after a successful vascular intervention for people with symptomatic peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) is characterised by obstruction or narrowing of the large arteries of the lower limbs, usually caused by atheromatous plaques. Most people with PAD who experience intermittent leg pain (intermittent claudication) are typically treated with secondary prevention strategies, including medical management and exercise therapy. Lower limb revascularisation may be suitable for people with significant disability and those who do not show satisfactory improvement after conservative treatment. Some studies have suggested that lower limb revascularisation for PAD may not confer significantly more benefits than supervised exercise alone for improved physical function and quality of life. It is proposed that supervised exercise therapy as adjunctive treatment after successful lower limb revascularisation may confer additional benefits, surpassing the effects conferred by either treatment alone. OBJECTIVES: To assess the effects of a supervised exercise programme versus standard care following successful lower limb revascularisation in people with PAD. SEARCH METHODS: We searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, two other databases, and two trial registers, most recently on 14 March 2023. SELECTION CRITERIA: We included randomised controlled trials which compared supervised exercise training following lower limb revascularisation with standard care following lower limb revascularisation in adults (18 years and older) with PAD. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were maximum walking distance or time (MWD/T) on the treadmill, six-minute walk test (6MWT) total distance, and pain-free walking distance or time (PFWD/T) on the treadmill. Our secondary outcomes were changes in the ankle-branchial index, all-cause mortality, changes in health-related quality-of-life scores, reintervention rates, and changes in subjective measures of physical function. We analysed continuous data by determining the mean difference (MD) and 95% confidence interval (CI), and dichotomous data by determining the odds ratio (OR) with corresponding 95% CI. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified seven studies involving 376 participants. All studies involved participants who received either additional supervised exercise or standard care after lower limb revascularisation. The studies' exercise programmes varied, and included supervised treadmill walking, combined exercise, and circuit training. The duration of exercise therapy ranged from six weeks to six months; follow-up time ranged from six weeks to five years. Standard care also varied between studies, including no treatment or advice to stop smoking, lifestyle modifications, or best medical treatment. We classified all studies as having some risk of bias concerns. The certainty of the evidence was very low due to the risk of bias, inconsistency, and imprecision. The meta-analysis included only a subset of studies due to concerns regarding data reporting, heterogeneity, and bias in most published research. The evidence was of very low certainty for all the review outcomes. Meta-analysis comparing changes in maximum walking distance from baseline to end of follow-up showed no improvement (MD 159.47 m, 95% CI -36.43 to 355.38; I2 = 0 %; 2 studies, 89 participants). In contrast, exercise may improve the absolute maximum walking distance at the end of follow-up compared to standard care (MD 301.89 m, 95% CI 138.13 to 465.65; I2 = 0 %; 2 studies, 108 participants). Moreover, we are very uncertain if there are differences in the changes in the six-minute walk test total distance from baseline to treatment end between exercise and standard care (MD 32.6 m, 95% CI -17.7 to 82.3; 1 study, 49 participants), and in the absolute values at the end of follow-up (MD 55.6 m, 95% CI -2.6 to 113.8; 1 study, 49 participants). Regarding pain-free walking distance, we are also very uncertain if there are differences in the mean changes in PFWD from baseline to treatment end between exercise and standard care (MD 167.41 m, 95% CI -11 to 345.83; I2 = 0%; 2 studies, 87 participants). We are very uncertain if there are differences in the absolute values of ankle-brachial index at the end of follow-up between the intervention and standard care (MD 0.01, 95% CI -0.11 to 0.12; I2 = 62%; 2 studies, 110 participants), in mortality rates at the end of follow-up (OR 0.92, 95% CI 0.42 to 2.00; I2 = 0%; 6 studies, 346 participants), health-related quality of life at the end of follow-up for the physical (MD 0.73, 95% CI -5.87 to 7.33; I2 = 64%; 2 studies, 105 participants) and mental component (MD 1.04, 95% CI -6.88 to 8.95; I2 = 70%; 2 studies, 105 participants) of the 36-item Short Form Health Survey. Finally, there may be little to no difference in reintervention rates at the end of follow-up between the intervention and standard care (OR 0.91, 95% CI 0.23 to 3.65; I2 = 65%; 5 studies, 252 participants). AUTHORS' CONCLUSIONS: There is very uncertain evidence that additional exercise therapy after successful lower limb revascularisation may improve absolute maximal walking distance at the end of follow-up compared to standard care. Evidence is also very uncertain about the effects of exercise on pain-free walking distance, six-minute walk test distance, quality of life, ankle-brachial index, mortality, and reintervention rates. Although it is not possible to confirm the effectiveness of supervised exercise compared to standard care for all outcomes, studies did not report any harm to participants from this intervention after lower limb revascularisation. Overall, the evidence incorporated into this review was very uncertain, and additional evidence is needed from large, well-designed, randomised controlled studies to more conclusively demonstrate the role additional exercise therapy has after lower limb revascularisation in people with PAD.

[Spinal cord electrical stimulation with neurophysiological monitoring for treatment of high-risk diabetic foot].

OBJECTIVE: To evaluate the clinical efficacy of a single-session implantation of spinal cord electrical stimulation with neurophysiological monitoring a spinal cord electrical stimulator under general anesthesia with neurophysiological monitoring for the treatment of high-risk diabetic foot. METHODS: The clinical data of seven patients with high-risk diabetic foot who underwent spinal cord electrical stimulation in neurosurgery ward nine of Tianjin Huanhu Hospital from May 2022 to May 2023 were collected. The operation was performed under general anesthesia with the "C" arm X ray machine guidance and neurophysiological monitoring. The arterial diameter and peak flow rate of lower extremity, lower extremity skin temperature (calf skin temperature, foot skin temperature), visual analog scale (VAS), continuous distance of movement, blood glucose level and toe wound were compared between patients before and after surgery. RESULTS: A total of seven patients with high-risk diabetic foot were included. The diameters and peak flow rates of femoral artery, popliteal artery, anterior tibial artery, posterior tibial artery and dorsal foot artery in both lower limbs were significantly improved after surgery. All patients had different degrees of lower limb pain before operation. After operation, VAS score decreased significantly (1.1±0.9 vs. 6.8±3.4), the pain was significantly relieved, and the calf skin temperature and foot skin temperature were significantly higher than those before surgery [calf skin temperature (centigrade): 33.3±0.9 vs. 30.9±0.7, foot skin temperature (centigrade): 31.4±0.8 vs. 29.1±0.6], fasting blood glucose and postprandial blood glucose were significantly lower than those before surgery [fasting blood glucose (mmol/L): 7.6±1.4 vs. 10.5±1.2, postprandial blood glucose (mmol/L): 9.3±2.3 vs. 13.5±1.1], the differences were statistically significant (all P < 0.01). The lower limb movement of all seven patients was significantly improved after surgery, including one patient who needed wheelchair travel before surgery, and one patient who had intermittent claudication before surgery. Among them, one patient needed wheelchair travel and one patient had intermittent claudication before surgery. All patients could walk normally at 2 weeks after operation. Among the seven patients, two patients had the diabetic foot wound ulceration before surgery, which could not heal for a long time. One month after surgery, blood flow around the foot wound recovered and the healing was accelerated. The wound was dry and crusted around the wound, and the wound healed well. CONCLUSIONS: For diabetic high-risk foot patients who are intolerant to diabetic peripheral neuralgia and local anesthesia spinal cord electrical stimulation test, one-time implantation of spinal cord electrical stimulator under general anesthesia under neurophysiological monitoring can effectively alleviate peripheral neuralgia and other diabetic foot related symptoms, improve lower limb blood supply, and reduce the risk of toe amputation. Clinical practice has proved the effectiveness of this technique, especially for the early treatment of diabetic high-risk foot patients.

Trends in Lower Extremity Artery Disease Repair Incidence, Comorbidity, and Mortality: A Danish Nationwide Cohort Study, 1996-2018.

Background: The prevalence of occlusive lower extremity artery disease (LEAD) is rising worldwide while European epidemiology data are scarce. We report incidence and mortality of LEAD repair in Denmark from 1996 through 2018, stratified on open aorto-iliac, open peripheral, and endovascular repair. Methods: A nationwide cohort study of prospective data from population-based Danish registers covering 1996 to 2018. Comorbidity was assessed by Charlson's Comorbidity Index (CCI). Incidence rate (IR) ratios and mortality rate ratios (MRR) were estimated by multivariable Poisson and Cox regression, respectively. Results: We identified 41,438 unique patients undergoing 46,236 incident first-time LEAD repairs by either aorto-iliac- (n=5213), peripheral surgery (n=18,665) or percutaneous transluminal angioplasty (PTA, n=22,358). From 1996 to 2018, the age- and sex-standardized IR for primary revascularization declined from 71.8 to 50.2 per 100,000 person-years (IRR, 0.70; 95% CI, 0.66-0.75). Following a 2.5-fold IR increase of PTA from 1996 to 2010, all three repair techniques showed a declining trend after 2010. The declining IR was driven by decreasing LEAD repair due to claudication, and by persons aged below 80 years, while the IR increased in persons aged above 80 years (p interaction<0.001). LEAD repair was more frequent in men (IRRfemale vs male, 0.78; 95% CI, 0.77-0.80), which was consistent over calendar time (p interaction=0.41). Crude mortality decreased following open/surgical repair, and increased following PTA, but all three techniques trended towards lower adjusted mortality comparing the start and the end of the study period (MRRaorto-iliac, 0.71; 95% CI, 0.54-0.93 vs MRRperipheral, 0.76; 95% CI, 0.69-0.83 vs MRRPTA, 0.96; 95% CI, 0.86-1.07). Increasing age and CCI, male sex, smoking, and care dependency associated with increased mortality. Conclusion: The incidence rate of LEAD repair decreased in Denmark from 1996 to 2018, especially in persons younger than 80 years, and primarily due to reduced revascularization for claudication. Adjusted mortality rates decreased following open surgery, but seemed unaltered following PTA.

The Use and Impact of Cilostazol on Patients Undergoing Endovascular Peripheral Interventions.

BACKGROUND: Cilostazol is used for the treatment of intermittent claudication. The impact of cilostazol on the outcomes of peripheral vascular interventions (PVIs) remains controversial. This study assesses the use and impact of cilostazol on patients undergoing PVI for peripheral arterial disease (PAD). METHODS: The Vascular Quality Initiative (VQI) database files for PVI were reviewed. Patients with PAD who underwent PVI for chronic limb threatening-ischemia or claudication were included and divided based on the use of cilostazol preoperatively. After propensity matching for patient demographics and comorbidities, the short-term and long-term outcomes of the 2 groups (preoperative cilostazol use versus no preoperative cilostazol use) were compared. The Kaplan-Meier method was used to determine outcomes. RESULTS: A total of 245,309 patients underwent PVI procedures and 6.6% (N = 16,366) were on cilostazol prior to intervention. Patients that received cilostazol were more likely to be male (62% vs 60%; P < 0.001), White (77% vs. 75%; P < 0.001), and smokers (83% vs. 77%; P < 0.001). They were less likely to have diabetes mellitus (50% vs. 56%; P < 0.001) and congestive heart failure (14% vs. 23%; P < 0.001). Patient on cilostazol were more likely to be treated for claudication (63% vs. 40%, P < 0.001), undergo prior lower extremity revascularization (55% vs. 51%, P < 0.001) and less likely to have undergone prior minor and major amputation (10% vs. 19%; P < 0.001) compared with patients who did not receive cilostazol. After 3:1 propensity matching, there were 50,265 patients included in the analysis with no differences in baseline characteristics. Patients on cilostazol were less likely to develop renal complications and more likely to be discharged home. Patients on cilostazol had significantly lower rates of long-term mortality (11.5% vs. 13.4%, P < 0.001 and major amputation (4.0% vs. 4.7%, P = 0.022). However, there were no significant differences in rates of reintervention, major adverse limb events, or patency after PVI. Amputation-free survival rates were significantly higher for patients on cilostazol, after 4 years of follow up (89% vs. 87%, P = 0.03). CONCLUSIONS: Cilostazol is underutilized in the VQI database and seems to be associated with improved amputation-free survival. Cilostazol therapy should be considered in all patients with PAD who can tolerate it prior to PVI.

High INtensity Interval Training in pATiEnts with Intermittent Claudication: A Qualitative Acceptability Study.

BACKGROUND: A novel high-intensity interval training (HIIT) program has demonstrated feasibility for patients with intermittent claudication (IC). The aim of this study was to explore patient perspectives of the HIIT program to inform refinement and future research. METHODS: All patients screened and eligible for the 'high intensity interval training in patients with intermittent claudication (INITIATE)' study were eligible to take part in a semistructured interview. A convenience subsample of patients was selected from 3 distinct groups: 1) those who completed the HIIT program, 2) those who prematurely discontinued the HIIT program, and 3) those who declined the HIIT program. Interviews considered patients views of the program and experiences of undertaking and/or being invited to undertake it. Interviews were audio recorded, transcribed verbatim, and analyzed via thematic analysis. RESULTS: Eleven out of 31 participants who completed the program and 12 out of 38 decliners were interviewed. No participants who withdrew from the program agreed to interview. The 3 key themes were; personal reflections of the program; program facilitators and barriers; and perceived benefits. Completers enjoyed taking part, reported symptomatic improvement and would complete it again. Practical and psychological barriers exist, such as transport and motivation. Changes to the program were suggested. CONCLUSIONS: Findings support the acceptability of this novel HIIT program, which in combination with the feasibility findings, suggest that a fully powered randomized controlled trial, comparing HIIT to usual-care supervised exercise programs is warranted.

Psychosocial and socioeconomic factors are most predictive of health status in patients with claudication.

BACKGROUND: As a key treatment goal for patients with symptomatic peripheral artery disease (PAD), improving health status has also become an important end point for clinical trials and performance-based care. An understanding of patient factors associated with 1-year PAD health status is lacking in patients with PAD. METHODS: The health status of 1073 consecutive patients with symptomatic PAD in the international multicenter PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry was measured at baseline and 1 year with the Peripheral Artery Questionnaire (PAQ). The association of 47 patient characteristics with 1-year PAQ scores was assessed using a random forest algorithm. Variables of clinical significance were retained and included in a hierarchical multivariable linear regression model predicting 1-year PAQ summary scores. RESULTS: The mean age of patients was 67.7 ± 9.3 years, and 37% were female. Variables with the highest importance ranking in predicting 1-year PAQ summary score were baseline PAQ summary score, Patient Health Questionnaire-8 depression score, Generalized Anxiety Disorder-2 anxiety score, new onset symptom presentation, insurance status, current or prior diagnosis of depression, low social support, initial invasive treatment, duration of symptoms, and race. The addition of 19 clinical variables in an extended model marginally improved the explained variance in 1-year health status (from R2 0.312 to 0.335). CONCLUSIONS: Patients' 1-year PAD-specific health status, as measured by the PAQ, can be predicted from 10 mostly psychosocial and socioeconomic patient characteristics including depression, anxiety, insurance status, social support, and symptoms. These characteristics should be validated and tested in other PAD cohorts so that this model can inform risk adjustment and prediction of PAD health status in comparative effectiveness research and performance-based care.

Comparison of endovascular therapies for chronic limb-threatening ischemia and claudication.

OBJECTIVE: Analysis of regional data from the Vascular Quality Initiative (VQI) suggested improved survival for patients undergoing stent placement compared with balloon angioplasty and atherectomy. Using national data from the VQI linked to Medicare claims data through the Vascular Implant Surveillance and Interventional Outcomes Network program, this study aimed to compare the rates of mortality, reintervention, and amputation after endovascular interventions (atherectomy, stenting, and balloon angioplasty) for two separate cohorts: patients with chronic limb-threatening ischemia (CLTI) and patients with claudication. METHODS: This was a secondary data analysis of Society for Vascular Surgery National VQI data linked to Medicare claims, between October 2016 and December 2019. Patients aged ≥65 years with symptoms of claudication or CLTI and a diagnosis of occlusive disease were included. Urgent or emergent interventions or those with concurrent procedures (endarterectomy, bypass, or bilateral intervention) were excluded. Interventions were grouped into (1) balloon angioplasty only; (2) stent (with or without balloon angioplasty); or (3) atherectomy (alone, with or without stent, with or without balloon angioplasty). Propensity score-matched cohorts were constructed to conduct pairwise intervention comparisons of mortality, reintervention, and amputation rates. Multivariable logistic regression was used to derive propensity scores for each patient. Kaplan-Meier estimates and Cox proportional hazards ratios (HRs) (95% confidence interval [CI]) analyses were performed. RESULTS: A total of 9785 (2665 claudication, 7120 CLTI) eligible patients were identified. After propensity score matching for the CLTI group, 2826, 3608, and 2796 pairs of cases were used to compare balloon angioplasty vs atherectomy, balloon angioplasty vs stent, and stent vs atherectomy, respectively. No statistically significant difference in mortality was observed among all interventions. However, atherectomy was associated with a significant increase in reintervention rate compared with balloon angioplasty (HR, 1.22; 95% CI, 1.06-1.39; P = .01) and compared with stenting (HR, 1.27; 95% CI, 1.10-1.46; P < .01) within the first year after the index procedure. Of note, both atherectomy (HR, 0.82; 95% CI, 0.68-0.98; P < .05) and stenting (HR, 0.76; 95% CI, 0.64-0.90; P < .01) showed lower rates of major amputation when compared with balloon angioplasty within 1 year after the index procedure. In the claudication group, there were no significant differences observed among interventions for peripheral arterial disease for mortality, reintervention, or amputation rates. CONCLUSIONS: Further studies are needed to identify appropriate indications for atherectomy, because there may be a subset of patients with CLTI who benefit from this therapy with respect to amputation rates. Until then, caution should be exercised when using atherectomy because it is also associated with higher reintervention rates.

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.

Uptake and outcomes of supervised exercise therapy for peripheral artery disease: The importance of vascular medicine specialists at a large midwestern health care system during the first 5 years of CMS reimbursement.

BACKGROUND: Supervised exercise therapy (SET) is the cornerstone of medical therapy for symptomatic peripheral artery disease (PAD). Despite the efficacy of SET, initial reports following the 2017 Centers for Medicare and Medicaid Services (CMS) reimbursement decision indicate low SET uptake, referral, and completion. Vascular medicine specialists are key to the success of such programs. We examined rates of SET referral, completion, and outcomes in a health system with a robust SET program during the first 5 years of CMS reimbursement. METHODS: A retrospective chart review of patients with PAD referred to SET between October 1, 2017 and December 31, 2022 was conducted. Patient demographic and medical characteristics, SET indication, referring provider specialty, SET participation (e.g., exercise modality, number of sessions, treadmill prescription), and outcomes were abstracted. Descriptive statistics, t-tests, and multiple linear regression were used to examine the sample, evaluate outcomes, and explore outcomes by relevant covariates (i.e., age, sex, referring provider specialty). RESULTS: Of 5320 patients with PAD, N = 773 were referred to SET; N = 415 enrolled and were included in the present study. Vascular medicine and vascular surgery specialists were the two primary sources of referrals (30.6% and 51.6%, respectively). A total of 207 patients (49.9%) completed SET. Statistically significant and clinically meaningful improvements were observed in all outcomes. CONCLUSION: SET referral and completion rates are low in the 5 years following CMS reimbursement, despite the advocacy of vascular medicine specialists. SET is effective in improving patient functional capacity and quality of life. Additional efforts are needed to increase both SET availability and referrals as part of comprehensive treatment of PAD.

Determination of Treatment Efficacy after Revascularization of Intermittent Claudication Patients by Physical Function Assessment.

PURPOSE: There have been few reports examining changes in physical activity (PA) after revascularization of lower extremities from the perspective of physical function at discharge. The purpose of this study was to clarify the effects of physical function before discharge on the amount of PA after discharge in patients who underwent revascularization. METHODS: The subjects were 34 Fontaine class II patients admitted for elective surgical revascularization or endovascular treatment at two hospitals from September 2017 to October 2019. Triaxial accelerometers were used to measure changes in sedentary behavior (SB) before admission and 1 month after discharge. Multiple regression analysis was performed on the 6-min walking distance (6MWD) at the time of discharge and the change in SB 1 month after discharge; the cutoff value was calculated from the receiver operating characteristic (ROC) curve. RESULTS: SB 1 month after discharge significantly decreased in the decreased SB group compared to the increased SB group (575.5 [400-745.2] vs. 649.5 [453.8-809.2], p <0.01). ROC curve was plotted with SB increase/decrease as the dependent variable and 6MWD at discharge as the independent variable; the cutoff value was 357.5 m. CONCLUSION: 6MWD measurement at discharge may help predict changes in SB after discharge.

Revascularization for claudication: Changing the natural history of a benign disease!

OBJECTIVE: The benign natural history of intermittent claudication was first documented in 1960 and has been reconfirmed in several subsequent studies. Excellent outcomes in patients with intermittent claudication can be achieved with exercise therapy and optimal medical management. Professional society guidelines have clearly stated that revascularization procedures should be performed only in patients with incapacitating claudication who have failed conservative therapy. Despite these guidelines, revascularization procedures, primarily percutaneous interventions, have been increasingly utilized in patients with claudication. Many of these patients are not even offered an attempt at medical therapy, and those who are often do not undergo a full course of treatment. Many studies document significant reintervention rates following revascularization, which are associated with increased rates of acute and chronic limb ischemia that may result in significant rates of amputation. The objectives of this study were to compare outcomes of conservative therapy to those seen in patients undergoing revascularization procedures and to determine the impact of revascularization on the natural history of claudication. METHODS: Google Scholar and PubMed were searched for manuscripts on the conservative management of claudication and for those reporting outcomes following revascularization for claudication. RESULTS: Despite early improvement in claudication symptoms following revascularization, multiple studies have demonstrated that long-term outcomes following revascularization are often no better than those obtained with conservative therapy. High reintervention rates (up to 43% for tibial atherectomies) result in high rates of both acute and chronic limb ischemia as compared with those patients undergoing medical therapy. In addition, amputation rates as high as 11% on long-term follow-up are seen in patients undergoing early revascularization. These patients also have a higher incidence of adverse cardiovascular events such as myocardial infarctions compared with patients treated medically. CONCLUSIONS: Revascularization procedures negatively impact the natural history of claudication often resulting in multiple interventions, an increase in the incidence of acute and chronic limb ischemia, and an increased risk of amputation. Accordingly, informed consent requires that all patients undergoing early revascularization must be appraised of the potential negative impact of revascularization on the natural history of claudication.

Test-retest Reliability and Minimal Detectable Change in Exercise Oximetry in Claudicants.

BACKGROUND: Exercise transcutaneous oxygen pressure measurement (Exercise-TcPO2) can be used to diagnose Lower Extremity Artery Disease (LEAD) and allows the quantification of limb ischemia during exercise on treadmill. Exercise-TcPO2 test-retest reliability in patients with LEAD and severe walking impairment is unknown. The aim of this study was to evaluate the test-retest reliability, standard error of measurement (SEM), and Minimal Detectable Change (MDC) of exercise-TcPO2 in patients with claudication. METHODS: Data were collected from patients that performed 2 treadmill tests within a 1-month interval. Delta from Rest of Oxygen Pressure (DROP) values were measured at both buttocks (proximal) and both calves (distal). Test-retest reproducibility was assessed by recording transcutaneous oximetry measurements twice and expressed as SEM and intra-class correlation coefficients. MDC was calculated using the formula MDC = SEM x 1.96 x √ 2. RESULTS: Twenty eight LEAD patients (61 ± 9 years old) were included. Intra-class correlation coefficients were 0.66 [0.50, 0.79] and 0.65 [0.49, 0.79] for the proximal and distal levels, respectively. The SEM of DROP at the proximal and distal levels were 7 [6, 9] mm Hg and 9 [8, 11] mm Hg, respectively. The SEM for all (proximal and distal) DROP values was 8 [7, 10] mm Hg and the MDC of DROP was 23 mm Hg. CONCLUSIONS: Exercise-TcPO2 with measurement of DROP values has a moderate test-retest reliability in LEAD patients with a maximal walking distance ≤ 300m. For an individual, an improvement or deterioration in DROP of ≥ 23 mm Hg after an intervention would be required to be 95% confident that the change is significant. It should be considered in evaluating the impact of treatment in patients with claudication.

Supervised Exercise Therapy for Intermittent Claudication: A Propensity Score Matched Analysis of Retrospective Data on Long Term Cardiovascular Outcomes.

OBJECTIVE: This study aimed to explore the long term outcomes of patients with intermittent claudication (IC) who completed supervised exercise therapy (SET) vs. those who declined or prematurely discontinued SET, focusing on the incidence of chronic limb threatening ischaemia (CLTI), revascularisation, major adverse limb events (MALE), and major adverse cardiovascular events (MACE). METHODS: A retrospective registry analysis of consecutive patients with IC who were referred for SET between March 2015 and August 2016 and followed up for a minimum of five years. Serial univariable analysis and logistic regression were performed to identify the statistically significant clinical variables that were independent predictors of each outcome measure. The resulting statistically significant variables were used to guide 1:1 propensity score matching (PSM) using the nearest neighbour method with a calliper of 0.2. Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between SET and the outcomes of interest. RESULTS: Two hundred and sixty-six patients were referred to SET between March 2015 and August 2016. Of these, 64 patients completed SET and 202 patients did not. After PSM, 49 patients were analysed in each cohort. The Cox proportional hazards analysis revealed a significant association between completion of SET and revascularisation requirement (HR 0.46 95% CI 0.25 - 0.84; p = .011), completion of SET and progression to CLTI (HR 0.091, 95% CI 0.04 - 0.24; p < .001), completion of SET and MACE (HR 0.52; 95% CI 0.28 - 0.99; p = .05) and completion of SET and MALE (HR 0.28, 95% CI 0.13 - 0.65; p = .003). The Harrell's C index for all of these models was greater than 0.75, indicating good predictive accuracy. CONCLUSION: Completion of SET is associated with better outcomes in patients who completed SET compared with patients who declined or discontinued SET with respect to clinically important cardiovascular outcomes over seven years.

Anatomic patterns in claudicants who fail supervised exercise therapy.

OBJECTIVE: Patients with intermittent claudication (IC) from peripheral arterial disease (PAD) have significant improvement with supervised exercise therapy (SET). However, many patients have progressive disease that will ultimately require revascularization. We sought to determine whether the anatomic patterns of PAD were associated with response to SET. METHODS: We prospectively enrolled patients with IC at the West Haven, Connecticut Veterans Health Administration between June 2019 and June 2022. Patients were classified based on the level of their arterial disease with >50% obstruction. SET failure was defined as progressive symptoms or development of critical limb-threatening ischemia (CLTI) requiring revascularization. RESULTS: Thirty-eight patients with PAD were included. Thirteen patients (34.2%) had significant common femoral artery (CFA) disease, and 25 (65.8%) had non-CFA disease. Over a median follow-up of 1407 days, 11 patients (84.6%) with CFA disease failed SET as compared with three patients (12.0%) with non-CFA disease (P < .001). Patients with CFA disease were more likely to develop CLTI (46.2% vs 4.0%; P = .001) and have persistent symptoms (38.5% vs 8.0%; P = .02). Patients with CFA disease had significantly lower post-SET ankle-brachial index (0.58 ± 0.14 vs 0.77 ± 0.19; P = .03). In multivariate analysis, the only variable associated with SET failure was CFA disease location (odds ratio, 68.75; 95% confidence interval, 5.05-936.44; P = .001). CONCLUSIONS: Patients with IC from high-grade CFA atherosclerosis are overwhelmingly likely to fail SET, potentially identifying a subset of patients who benefit from upfront revascularization.

Inflammation Is a Histological Characteristic of Skeletal Muscle in Chronic Limb Threatening Ischemia.

BACKGROUND: The loss of skeletal muscle is a prognostic factor in several diseases including in patients with chronic limb threatening ischemia (CLTI). Patients with CLTI also have a lower skeletal mass and area when compared to those with claudication. However, there are no currently available data regarding the histological characteristics of core muscles in patients with CLTI. This study aims to determine the differences in core skeletal muscles between patients with claudication and those with CLTI. The second aim is to evaluate the differences in myokines, which are molecules secreted by skeletal muscle, between patients with claudication and those with CLTI. METHODS: An observational, prospective study was conducted from January 2018 to July 2022 involving consecutive patients with peripheral arterial disease (PAD). The clinical characteristics were registered. In PAD patients with surgical indication for common femoral artery approach, samples of sartorius skeletal muscle (and not from the limb muscles directly involved in the ischemic process) were collected. The samples were submitted to histological characterization on hematoxylin-eosin and to immunohistochemical analysis to detect CD45+ leukocytes and CD163+ macrophages. The extent of the inflammatory cells (leukocytes and macrophages) was semiquantitatively assessed using a 0-to-4 grade scale as follows: absent (0†), mild (†), moderate (††), severe (†††), and very severe (††††). Serum levels of myokines: irisin, myostatin, IL-8, and lL-6 were determined with multiplex bead-based immunoassay. RESULTS: 119 patients (mean age: 67.58 ± 9.60 years old, 79.80% males) 64 with claudication and 54 with CLTI were enrolled in the study. No differences were registered between patients with claudication and those with CLTI on age, gender, cardiovascular risk factors, and medication, except on smoking habits. There was a significantly higher prevalence of smokers and a higher smoking load in the claudication group. Samples of sartorius skeletal muscle from 40 patients (14 with claudication and 26 with CLTI) were submitted to histological analysis. No differences were found in skeletal muscle fibers preservation, trauma, or hemorrhage (on hematoxylin-eosin staining). However, in the immunohistochemistry study, we found more inflammatory cells CD45+ leukocytes in patients with CLTI when compared to those with claudication [CD45+ ≥ moderate (††): claudication (n = 14): 4; 28.57%; CLTI (n = 25): 16; 64.00%; P = 0.034]. Patients with CLTI also had higher tissue levels of CD163+ macrophages, but this difference was not significant [CD163+ ≥ moderate (††): claudication (n = 13): 7; 53.85%; CLTI (n = 27): 21; 77.78%; P = 0.122]. The serum levels of the myokines, irisin, and myostatin were below the lower limit of detection, in the majority of patients, so no valid results were obtained. However, patients with CLTI had a higher serum level of Interleukin (IL)-6 and IL-8. CONCLUSIONS: CLTI patients exhibit increased quantities of leukocytes in their sartorius muscle, as well as elevated serum levels of myokines IL-8 and IL-6. Inflamed skeletal muscle can contribute to the loss of muscle mass and account for the lower density of skeletal muscle observed in CLTI. Additionally, inflamed skeletal muscle may contribute to the development of systemic inflammation through the secretion of pro-inflammatory cytokines into the systemic circulation. Halting the inflammatory process could eventually improve the prognosis of CLTI patients.

Long-Term Results of Thoracofemoral Bypass in the Initial Treatment of Juxtarenal Total Aortic Occlusion.

BACKGROUND: Thoracofemoral bypass has been applied mostly secondary to previous procedures in the treatment of aortoiliac occlusive disease. However, its application as an initial treatment is less common, and long-term outcomes remain uncertain. The aim of this analysis was to review the 16-year experience and long-term outcomes of 31 consecutive patients who underwent thoracofemoral bypass as the primary procedure. METHODS: All patients who underwent thoracofemoral bypass for severe aortoiliac occlusive disease between 2005 and 2021 were retrospectively analyzed. The occlusion and calcified plaques of the abdominal aorta at the renal level were common characteristics of all patients. The patients were divided into 2 groups: severe claudication group (Rutherford III group) and chronic limb-threatening ischemia group (Rutherford IV-V). Chi-square test or Fisher's exact test was used to compare categorical variables between the groups, and t-test or Mann-Whitney U-tests were used to compare continuous variables according to their distributions. The Kaplan-Meier curve was used to depict the time-to-event data. RESULTS: Thirty-one patients [age: 62 (56-67.5); male: 87%] underwent thoracofemoral bypass. Among the 31 patients, 21 (67.7%) belonged to the severe claudication group (Rutherford III), while 10 (32.3%) were in the chronic limb-threatening ischemia (Rutherford IV-V). Twenty-two patients (83.8%) remained asymptomatic after thoracofemoral bypass. The mean follow-up duration was 79 ± 32 months. The 30-day mortality rate was 3.2% (n = 1). Major complications were observed in 9.6% of patients (n = 3; respiratory: 6.4%, retroperitoneal hematoma: 3.2%). No significant difference was found between the claudication and chronic limb-threatening ischemia groups regarding major complications (3.2% vs. 6.4%, P = NS). Minor complications occurred in 41.9% of patients, including pleural effusion 9.6% (n = 3), acute kidney injury 9.6% (n = 3), gastrointestinal bleeding 3.2% (n = 1), paralytic ileus 6.4% (n = 2), and superficial skin infection 12.9% (n = 4). The rate of postoperative superficial skin infection was higher in the chronic limb-threatening ischemia group compared to the claudication group (4 [40%] vs. 0 [0%], P: 0.007). The univariable Cox regression analysis revealed that hypertension and diabetes mellitus were not related to primary patency of the thoracofemoral bypass graft. The 5-year Kaplan-Meier estimated primary patency for the entire study was 96% ± 7% (95% confidence interval [CI]: 88.6-100), and the secondary patency was 96.3% ± 6% (95% CI: 89.4-100). The 5-year Kaplan-Meier estimated survival rate after thoracofemoral bypass was 93.4% ± 3 (95% CI: 91-100). CONCLUSIONS: We demonstrated in this study that thoracofemoral bypass can yield good outcomes when preferred as the initial treatment in selected patients with juxtarenal total aortic occlusion. Despite being a complex surgical technique, thoracofemoral bypass has shown to have safe, acceptable mortality and morbidity rates, as well as excellent long-term follow-up results in selected patients.

A meta-analysis of the medium- to long-term outcomes in patients with chronic deep venous disease treated with dedicated venous stents.

OBJECTIVE: This review summarizes the safety profile, stent patency, and clinical effectiveness of dedicated venous stents for the treatment of chronic deep venous disease. The approaches to stenting and post-procedural management of different vascular units are also explored. METHODS: The MEDLINE and Embase databases were searched for pertinent literature published from January 2010 to January 2023. Outcomes related to post-stenting symptoms and health-related quality of life were described narratively. A meta analysis was conducted to evaluate stent patency, ulcer healing, bleeding, and 30-day stent thrombosis, and these outcomes were presented as proportion event rates. RESULTS: Seventeen studies were identified comprising of 2218 patients. 62.7% of individuals had post-thrombotic stenosis or occlusion. The majority of patients (78.6%) were noted to have complete occlusions of their deep veins before stenting. Eleven different dedicated venous stents were deployed. At 12 months, the primary patency rate was 83% (95% confidence interval [CI]: 76%-90%), the primary-assisted patency rate was 90% (95% CI: 85%-96%), and the secondary patency rate was 95% (95% CI: 92%-98%). A significant improvement in health-related quality of life was demonstrated after intervention. In total, 68.8% (95% CI: 52.0%-83.7%) of ulcers healed at the last follow-up. The remaining symptomatic changes were described narratively; improvements in pain, venous claudication, and edema after stenting were observed. Seventeen deaths occurred, but none were linked to the stenting procedures. A total of 159 cases (7.2% of patients) of in-stent stenosis were observed, whereas 110 stents (5.0% of patients) were occluded. The incidence of major and minor bleeding was 1.7% (95% CI: 1.0%-2.5%) and 3.2% (95% CI: 1.3%-5.6%), respectively, more commonly seen in patients undergoing hybrid intervention. CONCLUSIONS: Deep venous stenting using dedicated venous stents is a safe technique to treat chronic deep venous stenosis and/or occlusion. Within the limitations of this study, deep venous stenting is associated with good patency rates and symptomatic improvement.

Do Sociodemographic, Behavioral, Clinical, and Anthropometric Factors Influence the Association Between Sex and Functional Capacity in Patients with Peripheral Arterial Disease?

BACKGROUND: To explore the influence of sociodemographic, behavioral, clinical, and anthropometric factors on the association between sex and functional capacity in patients with peripheral arterial disease. METHODS: A cross-sectional study was conducted with patients aged more than 45 years, diagnosed with peripheral artery disease (PAD), from 2 Brazilian hospitals. Data on sociodemographic characteristics, behavioral risk factors, clinical profile, and anthropometric measurements were collected. Functional capacity was assessed using the 6-min walk test and the Walking Impairment Questionnaire. Statistical analyses, including t-tests, chi-square tests, and logistic regression, were performed to assess the relationships between sex, functional capacity, and potential influencing factors. RESULTS: Among the 262 patients with PAD, 67 were women and 113 were men. Women exhibited lower absolute functional capacity and lower Walking Impairment Questionnaire scores compared to men, even after adjusting for potential confounders. However, relative functional capacity did not significantly differ between sexes after adjusting for variables. Pain-free walking distance was also lower in women compared to that in men, but this association lost significance after adjusting for sociodemographic factors. CONCLUSIONS: Women with PAD had lower absolute functional capacity compared to men, influenced by various factors such as sociodemographic, behavioral, clinical, and anthropometric factors. However, the relative functional capacity was similar between genders, being influenced only by behavioral factors, while for the distance walked until pain, the association was lost after adjustments for sociodemographic factors.