Risk factors for and risk of all-cause and atherosclerotic cardiovascular disease mortality in people with type 2 diabetes and peripheral artery disease: an observational, register-based cohort study.

BACKGROUND: Type 2 diabetes (T2D) and peripheral artery disease (PAD) are recognized as independent risk factors contributing to excess mortality. Contemporary observational studies exploring the associations of risk factors, and risk of all-cause and atherosclerotic cardiovascular disease mortality in persons with T2D following the onset of incident peripheral artery disease are limited. The objectives of this study were to investigate the associations of risk factors, and assess mortality risks in people with T2D compared with controls without T2D after the onset of PAD. METHODS: All persons with T2D (n = 150,215) registered in the Swedish National Diabetes Register between 2005 and 2009 were included, along with 346,423 controls without T2D matched for sex and age. Data were retrieved from several national registries, capturing information on risk factors, onset of incident peripheral artery disease, other comorbidities, socioeconomic factors, and outcomes. To compare persons with T2D and controls following the onset of peripheral artery disease regarding the risk of all-cause, and atherosclerotic cardiovascular disease mortality, Cox proportional hazard models and Kaplan-Meier curves were employed. A gradient-boosting model was utilized to estimate the relative statistical contribution of risk factors to the modeling of incident mortality risk in people with both T2D and peripheral artery disease. RESULTS: Crude rates of incident all-cause mortality were higher in individuals with T2D compared with controls, following the onset of PAD (600.4 (95% CI, 581.4-619.8) per 10,000 person-years versus 549.1 (95% CI, 532.1-566.5) per 10,000 person-years). Persons with T2D had an adjusted hazard ratio (HR) for all-cause mortality of 1.12 (95% CI, 1.05-1.19, P < 0.01) compared with controls after onset of incident PAD. The comparable adjusted HR for cardiovascular mortality was 1.13 (95% CI, 1.07-1.19, P < 0.01). High age and hyperglycemia at baseline played a significant role in contributing to the predictive models for incident all-cause and cardiovascular mortality among individuals with both T2D and PAD. CONCLUSIONS: The presence of T2D with concomitant PAD is related to an increased risk of both all-cause and cardiovascular mortality compared with individuals with only PAD. This argues for implementing optimized and intensive treatment strategies for individuals with both conditions.

Targeting Mitochondrial Dynamics during Lower-Limb Ischemia Reperfusion in Young and Old Mice: Effect of Mitochondrial Fission Inhibitor-1 (mDivi-1).

Peripheral arterial disease (PAD) strikes more than 200 million people worldwide and has a severe prognosis by potentially leading to limb amputation and/or death, particularly in older patients. Skeletal muscle mitochondrial dysfunctions and oxidative stress play major roles in this disease in relation with ischemia-reperfusion (IR) cycles. Mitochondrial dynamics through impairment of fission-fusion balance may contribute to skeletal muscle pathophysiology, but no data were reported in the setting of lower-limb IR despite the need for new therapeutic options. We, therefore, investigated the potential protective effect of mitochondrial division inhibitor-1 (mDivi-1; 50 mg/kg) in young (23 weeks) and old (83 weeks) mice submitted to two-hour ischemia followed by two-hour reperfusion on systemic lactate, muscle mitochondrial respiration and calcium retention capacity, and on transcripts specific for oxidative stress and mitochondrial dynamics. At the systemic levels, an IR-related increase in circulating lactate was still major despite mDivi-1 use (+305.9% p < 0.0001, and +269.4% p < 0.0001 in young and old mice, respectively). Further, IR-induced skeletal muscle mitochondrial dysfunctions (more severely impaired mitochondrial respiration in old mice (OXPHOS CI state, -68.2% p < 0.0001 and -84.9% p < 0.0001 in 23- and 83-week mice) and reduced calcium retention capacity (-46.1% p < 0.001 and -48.2% p = 0.09, respectively) were not corrected by mDivi-1 preconditioning, whatever the age. Further, mDivi-1 treatment did not oppose superoxide anion production (+71.4% p < 0.0001 and +37.5% p < 0.05, respectively). At the transcript level, markers of antioxidant enzymes (SOD 1, SOD 2, catalase, and GPx) and fission markers (Drp1, Fis) remained unchanged or tended to be decreased in the ischemic leg. Fusion markers such as mitofusin 1 or 2 decreased significantly after IR in both groups. In conclusion, aging enhanced the deleterious effects or IR on muscle mitochondrial respiration, and in this setting of lower-limb IR, mDivi-1 failed to protect the skeletal muscle both in young and old mice.

Quantitative Benefit-Risk Evaluation of Rivaroxaban in Patients After Peripheral Arterial Revascularization: The VOYAGER PAD Trial.

BACKGROUND: The VOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) trial compared rivaroxaban (2.5 mg twice a day) plus aspirin with aspirin alone in patients with symptomatic peripheral artery disease requiring endovascular or surgical limb revascularization, with 50% receiving clopidogrel background therapy. The New Drug Indication application includes benefit-risk assessments using clinical judgment to balance benefits against risks. During its review, the US Food and Drug Administration requested additional quantitative benefit-risk analyses with formal weighting approaches. METHODS AND RESULTS: Benefits and risks were assessed using rate differences between treatment groups (unweighted analysis). To account for clinical importance of the end points, a multi-criteria decision analysis was conducted using health state utility values as weights. Monte Carlo simulations incorporated statistical uncertainties of the event rates and utility weights. Intent-to-treat and on-treatment analyses were conducted. For unweighted intent-to-treat analyses, rivaroxaban plus aspirin would result in 120 (95% CI, -208 to -32) fewer events of the primary composite end point (per 10 000 patient-years) compared with aspirin alone. Rivaroxaban caused an excess of 40 (95% CI, 8-72) Thrombolysis in Myocardial Infarction major bleeding events, which was largely driven by nonfatal, nonintracranial hemorrhage Thrombolysis in Myocardial Infarction major bleeding events. For weighted analyses, rivaroxaban resulted in the utility equivalent of 13.7 (95% CI, -85.3 to 52.6) and 68.1 (95% CI, 7.9-135.7) fewer deaths per 10 000 patient-years (intent-to-treat and on-treatment, respectively), corresponding to probabilities of 64.4% and 98.7%, respectively, that benefits outweigh risks favoring rivaroxaban per Monte Carlo simulation. CONCLUSIONS: These analyses show a favorable benefit-risk profile of rivaroxaban therapy in the VOYAGER PAD trial, with findings generally consistent between the unweighted and weighted approaches.

Early Mortality, Cardiovascular, and Renal Diseases in Women's Lives Following Hypertensive Disorders of Pregnancy: The Prospective Nationwide Study CONCEPTION.

BACKGROUND: We aimed to evaluate the impact of hypertensive disorders of pregnancy occurrence, recurrence, onset time, and severity on mortality and on a wide range of cardiovascular outcomes in France. METHODS AND RESULTS: CONCEPTION (Cohort of Cardiovascular Diseases in Pregnancy) is a French nationwide prospective cohort using data from the National Health Data System. We included all women in CONCEPTION with no history of a cardiovascular event who delivered in France for the first time between 2010 and 2018 (N=2 819 655). Hypertensive disorders of pregnancy and cardiovascular outcomes during the study follow-up were identified using algorithms combining International Classification of Diseases, Tenth Revision (ICD-10) coded diagnoses during hospitalization and purchases of medication between 2010 and 2021. We fitted Cox models with time-varying exposure to assess the associations of hypertensive disorders of pregnancy with mortality and cardiovascular events. Women with gestational hypertension had a 1.25- to 2-fold higher risk of stroke, acute coronary syndrome, peripheral arterial disease, pulmonary embolism, and chronic kidney disease, and a 2- to 4-fold higher risk of rhythm and conduction disorder and heart failure. Women with preeclampsia had a 1.35- to 2-fold higher risk of rhythm or conduction disorder and pulmonary embolism during follow-up; a 2- to 4-fold higher risk of stroke, acute coronary syndrome, and peripheral arterial disease; and a 7- to 9-fold higher risk of heart failure and chronic kidney disease. They were 1.8 times more likely to die and 4.4 times more likely to die of cardiovascular causes. CONCLUSIONS: Hypertensive disorders of pregnancy drastically increase the risk of mortality, cardiovascular, and renal events early after pregnancy. Recurrent, severe, and early-onset preeclampsia further increases this risk.

Reversion of the Inflammatory Markers in Patients With Chronic Limb-Threatening Ischemia.

BACKGROUND: Peripheral artery disease is characterized by an intense inflammatory process that can be associated with a higher mortality rate, particularly in chronic limb-threatening ischemia (CLTI). This study aims to compare the evolution of inflammatory markers between patients with claudication with those with CLTI at 3, 6, and 12 months. METHODS AND RESULTS: An observational, single-center, and prospective study was conducted. A total of 119 patients with peripheral artery disease (65 with claudication and 54 with CLTI) were observed and inflammatory markers collected at admission and 3, 6, and 12 months. At admission, patients with CLTI, when compared with patients with claudication, had significantly higher serum levels of C-reactive protein and fibrinogen (positive acute-phase proteins) and lower serum level of albumin, total cholesterol, and high-density lipoprotein (negative acute-phase proteins): C-reactive protein (g/dL), 2.90 (25th-75th percentile, 2.90-4.90) versus 6.80 (25th-75th percentile, 2.90-53.26) (P=0.000); fibrinogen (mg/dL), 293.00 (25th-75th percentile, 269.25-349.00) versus 415.50 (25th-75th percentile, 312.00-615.75) (P=0.000); total cholesterol (mg/dL), 161.79±95% [152.74-170.85] versus 146.42%±95% [135.30-157.53] (P=0.034); high-density lipoprotein (mg/dL), 50.00 (25th-75th percentile, 41.00-60.00) versus 37.00 (25th-75th percentile, 30.00-45.50) (P=0.000); albumin (g/dL): 4.00 (25th-75th percentile, 3.70-4.20) versus 3.60 (25th-75th percentile, 3.10-4.00) (P=0.003). The association between CLTI and total cholesterol was lost after adjusting for confounders. Three months after the resolution of the CLTI, there was an increase in the levels of negative acute-phase proteins and a decrease in positive acute-phase proteins. These inflammatory proteins did not register an evolution in patients with claudication. The differences in the inflammatory proteins between groups disappeared at 6 months. CONCLUSIONS: CLTI has an inflammatory environment that can be partially reverted after resolution of the ischemic process, emphasizing the importance of timely intervention.

Transcriptomics analysis of long non-coding RNAs in smooth muscle cells from patients with peripheral artery disease and diabetes mellitus.

Diabetes mellitus (DM) is a significant risk factor for peripheral arterial disease (PAD), and PAD is an independent predictor of cardiovascular disorders (CVDs). Growing evidence suggests that long non-coding RNAs (lncRNAs) significantly contribute to disease development and underlying complications, particularly affecting smooth muscle cells (SMCs). So far, no study has focused on transcriptome analysis of lncRNAs in PAD patients with and without DM. Tissue samples were obtained from our Vascular Biobank. Due to the sample's heterogeneity, expression analysis of lncRNAs in whole tissue detected only ACTA2-AS1 with a 4.9-fold increase in PAD patients with DM. In contrast, transcriptomics of SMCs revealed 28 lncRNAs significantly differentially expressed between PAD with and without DM (FDR < 0.1). Sixteen lncRNAs were of unknown function, six were described in cancer, one connected with macrophages polarisation, and four were associated with CVDs, mainly with SMC function and phenotypic switch (NEAT1, MIR100HG, HIF1A-AS3, and MRI29B2CHG). The enrichment analysis detected additional lncRNAs H19, CARMN, FTX, and MEG3 linked with DM. Our study revealed several lncRNAs in diabetic PAD patients associated with the physiological function of SMCs. These lncRNAs might serve as potential therapeutic targets to improve the function of SMCs within the diseased tissue and, thus, the clinical outcome.

Pedal medial arterial calcification in diabetic foot ulcers: A significant risk factor of amputation and mortality.

AIMS: Pedal medial arterial calcification (MAC) is frequently observed in individuals with diabetic foot ulcers (DFUs). However, the impact of pedal MAC on individuals with DFUs remains uncertain. The main aim of this study was to evaluate the association between pedal MAC with amputation and mortality outcomes. METHODS: A prospective, observational cohort study was conducted at West China Hospital from January 2012 to December 2021. Logistic regression analyses, Kaplan-Meier survival method, and Cox proportional hazards models were employed to evaluate the relationship between pedal MAC and amputation as well as mortality. RESULTS: A total of 979 patients were enrolled in the study. Peripheral artery disease (PAD) was observed in 53% of patients with DFUs, and pedal MAC was found in 8%. Over a median follow-up of 46 (23-72) months, foot amputation was performed on 190 patients, and mortality occurred in 246 patients. Pedal MAC showed a significant association with amputation both in unadjusted analysis (odds ratio [OR] = 2.98, 95% confidence interval [CI] = 1.86-4.76, p < .001) and after adjusting sex, age, albumin levels, hemoglobin levels, and diabetic retinopathy status (OR 2.29, 95% CI 1.33-3.93, p = .003). The risk of amputation was found to be twofold higher in individuals with PAD and pedal MAC compared to those with PAD alone (OR 2.05, 95% CI 1.10-3.82, p = .024). Furthermore, the presence of pedal MAC was significantly associated with an increased risk of mortality (p = .005), particularly among individuals with DFUs but without PAD (HR 4.26, 95% CI 1.90-9.52, p < .001), rather than in individuals presenting with both DFUs and PAD. CONCLUSION: The presence of pedal MAC is significantly associated with both amputation and mortality in individuals with DFUs. Moreover, pedal MAC could provide additional value to predict amputation other than PAD.

Uncertainty quantification of the impact of peripheral arterial disease on abdominal aortic aneurysms in blood flow simulations.

Peripheral arterial disease (PAD) and abdominal aortic aneurysms (AAAs) often coexist and pose significant risks of mortality, yet their mutual interactions remain largely unexplored. Here, we introduce a fluid mechanics model designed to simulate the haemodynamic impact of PAD on AAA-associated risk factors. Our focus lies on quantifying the uncertainty inherent in controlling the flow rates within PAD-affected vessels and predicting AAA risk factors derived from wall shear stress. We perform a sensitivity analysis on nine critical model parameters through simulations of three-dimensional blood flow within a comprehensive arterial geometry. Our results show effective control of the flow rates using two-element Windkessel models, although specific outlets need attention. Quantities of interest like endothelial cell activation potential (ECAP) and relative residence time are instructive for identifying high-risk regions, with ECAP showing greater reliability and adaptability. Our analysis reveals that the uncertainty in the quantities of interest is 187% of that of the input parameters. Notably, parameters governing the amplitude and frequency of the inlet velocity exert the strongest influence on the risk factors' variability and warrant precise determination. This study forms the foundation for patient-specific simulations involving PAD and AAAs which should ultimately improve patient outcomes and reduce associated mortality rates.

Sex differences in outcomes after revascularization for acute lower limb ischemia: Propensity score adjusted analysis.

BACKGROUND: Previous reports have suggested higher rates of mortality and amputation for female patients in acute lower limb ischemia (ALI). The aims of the present study were to investigate if there is a difference in mortality, amputation, and fasciotomy between the sexes. METHODS: A retrospective cohort study of consecutive patients undergoing index revascularization for ALI between 2001 and 2018 was conducted. A propensity score was created through a logistic regression with female/male sex as an outcome. Cox regression analyses for 90-day and 1-year mortality, combining major amputation/mortality, and logistic regression for major bleeding and fasciotomy, were performed. All analyses were performed with and without adjusting for propensity score. RESULTS: A total of 709 patients were included in the study of which 45.9% were women. Mean age was 72.1 years. Females were older and had higher rates of atrial fibrillation, embolic disease, and lower estimated glomerular filtration rate, while men more often had anemia and chronic peripheral arterial disease. Mortality at 1 year was 21.2% for women and 14.7% for men. The adjusted hazard ratio for 1-year mortality was 0.99 (95% CI 0.67-1.46). Fasciotomy was performed in 7.1% of female and 12.8% of male patients; the adjusted odds ratio was 0.52 (95% CI 0.29-0.91). CONCLUSION: Sex was not found to be an independent risk factor for mortality or combined major amputation/mortality after revascularization for acute lower limb ischemia, whereas women had lower odds of undergoing fasciotomy. Whether women are underdiagnosed or do not develop acute compartment syndrome in the lower leg as often as men should be evaluated prospectively.

Methods, design, and initial results of an angiographic core lab from VOYAGER-PAD.

Background: Anatomy is critical in risk stratification and therapeutic decision making in coronary disease. The relationship between anatomy and outcomes is not well described in PAD. We sought to develop an angiographic core lab within the VOYAGER-PAD trial. The current report describes the methods of creating this core lab, its study population, and baseline anatomic variables. Methods: Patients undergoing lower-extremity revascularization for symptomatic PAD were randomized in VOYAGER-PAD. The median follow up was 2.25 years. Events were adjudicated by a blinded Clinical Endpoint Committee. Angiograms were collected from study participants; those with available angiograms formed this core lab cohort. Angiograms were scored for anatomic and flow characteristics by trained reviewers blinded to treatment. Ten percent of angiograms were evaluated independently by two reviewers; inter-rater agreement was assessed. Clinical characteristics and the treatment effect of rivaroxaban were compared between the core lab cohort and noncore lab participants. Anatomic data by segment were analyzed. Results: Of 6564 participants randomized in VOYAGER-PAD, catheter-based angiograms from 1666 patients were obtained for this core lab. Anatomic and flow characteristics were collected across 16 anatomic segments by 15 reviewers. Concordance between reviewers for anatomic and flow variables across segments was 90.5% (24,417/26,968). Clinical characteristics were similar between patients in the core lab and those not included. The effect of rivaroxaban on the primary efficacy and safety outcomes was also similar. Conclusions: The VOYAGER-PAD angiographic core lab provides an opportunity to correlate PAD anatomy with independently adjudicated outcomes and provide insights into therapy for PAD. (ClinicalTrials.gov Identifier: NCT02504216).

Gujarati translation, validity and reliability of Walking Impairment Questionnaire in people with intermittent claudication due to peripheral artery disease.

INTRODUCTION: The Walking Impairment Questionnaire (WIQ) is a common and easy-to-use assessment of walking incapacity in people with claudication due to peripheral artery disease (PAD). It has four subscales: pain severity, walking distance, walking speed, and ability to climb stairs. It has not been translated into Gujarati, which limits its use in Indian subjects. AIM: This study aims to translate and assess the validity and reliability of a Gujarati version of WIQ. MATERIALS AND METHODS: This study had three phases: 1. Forward and backward translation and Cultural adaptation of WIQ into the Gujarati language by two independent translators, 2. Face and content validation by six clinical reviewers and 10 participants with PAD and Type II diabetes, 3. Concurrent and construct validity, test-retest reliability, and internal consistency of Gujarati, the WIQ was assessed on 160 participants with PAD and Type II diabetes who had a mean Ankle Brachial Index (standard deviation) <0.40 (0.1). The concurrent and construct validity of the WIQ was analyzed by correlating the WIQ distance and speed score with 6-minute walk distance (6MWD) and speed and WIQ total score with the Medical Outcome Study Questionnaire Short Form 36 (SF-36) score using Pearson's correlation coefficient. Test-retest reliability was analyzed using an intraclass correlation coefficient (ICC) with a seven-day interval between two questionnaire applications. Internal consistency of the total WIQ score was determined using Cronbach's alpha. RESULTS: Following translation, the Gujarati WIQ was considered acceptable and understandable by people with PAD. There was excellent correlation between the WIQ distance score and 6-minute walk test distance (r = 0.95, P < .05)) , the WIQ speed score and 6-minute walk test speed score (r = 0.89, P < .05)) and the Gujarati WIQ total score and total score of physical functioning domain of SF- 36 (r = 0.99, P < .05). There was excellent test-retest reliability over 7 days for total WIQ score (ICC = 0.94). The Cronbach's alpha for internal consistency of 0.97 for total WIQ score were excellent. This demonstrates the sufficient homogeneity of the total questionnaire. CONCLUSION: The Gujarati version of the WIQ is reliable and valid and can be used to assess self-reported walking impairment in Gujarati-speaking people with PAD and Type II Diabetes.

Comparison of home-based rehabilitation and a centre-based exercise in terms of functional capacity, muscle oxygenation and quality of life in people with peripheral arterial disease: a protocol for a randomised controlled trial.

INTRODUCTION: Peripheral arterial disease (PAD) is increasingly prevalent, and supervised physical exercise programmes are recommended as the first-line treatment. However, these programmes are underused. Alternative delivery models may be able to expand treatment coverage. The objective of this study was to compare a home-based exercise programme (HBEP) and a centre-based exercise (CBE) in terms of their effects on functional capacity, peripheral muscle oxygenation and quality of life in individuals with PAD. METHODS AND ANALYSIS: This single-blind, parallel randomised clinical trial will consist of two groups: HBEP and CBE. A qualitative analysis will be carried out to investigate acceptability and satisfaction. The primary outcome will be functional capacity, assessed by the incremental shuttle walk test. Secondary outcomes will include functional capacity, assessed by a treadmill walking test; peripheral muscle oxygenation and quality of life; and self-reported functional impairment, risk factors, morbidity, level of physical activity, adherence, acceptability and satisfaction. The intervention protocols will consist of 12 weeks of intermittent walking until claudication symptoms, three times a week. Participants randomly assigned to the CBE group will participate in supervised face-to-face sessions. The HBEP group will perform exercises at home with remote supervision, monitored by a pedometer and heart rate monitor, and subjective perception of effort during each session will be recorded by participants in a training diary; follow-up will be conducted by telephone calls. Statistical analyses will follow the intention-to-treat principle. Participants allocated to the HBEP group will be interviewed about their experience of remote treatment using a qualitative approach. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of the Universidade Federal de Minas Gerais. The results will be disseminated in a peer-reviewed journal and presented at international congresses. This research has the potential to improve the care of people with PAD because if home-based rehabilitation demonstrates effectiveness, it could be considered an alternative or support resource to the usual centre-based treatment models, expanding access, coverage and participation in vascular physiotherapy TRIAL REGISTRATION: https://ensaiosclinicos.gov.br/rg/RBR-97vy9n7 on 14 April 2022.

Three-year clinical course after fluoropolymer-based drug-eluting stent implantation for femoropopliteal lesions.

BACKGROUND: Although the 1-year clinical outcomes of fluoropolymer-based drug-eluting stents (FP-DES) were favorable for the treatment of real-world femoropopliteal lesions in symptomatic peripheral artery disease (PAD), their performance beyond 1 year remained unknown. The current study determined the 3-year clinical course of FP-DES implantation for real-world femoropopliteal lesions. METHODS: This multicenter, prospective, observational study evaluated 1204 limbs (chronic limb-threatening ischemia, 34.8%; mean lesion length, 18.6 ± 9.9 cm, chronic total occlusion: 53.2%) of 1097 patients with PAD (age, 75 ± 9 years; diabetes mellitus, 60.8%) undergoing FP-DES implantation for femoropopliteal lesions. The primary outcome measure was 3-year restenosis. The secondary outcome measures included 3-year occlusive restenosis, stent thrombosis, target lesion revascularization (TLR), and aneurysmal degeneration. RESULTS: The 3-year cumulative occurrence of restenosis was 27.3%, whereas that of occlusive restenosis, stent thrombosis, and TLR was 16.1%, 7.3%, and 19.6%, respectively. The annual occurrence of restenosis decreased by 12.0%, 9.5%, and 5.8% in the first, second, and third year, respectively (p < 0.001). Similarly, the rates of occlusive restenosis and stent thrombosis decreased (p < 0.001 and p = 0.007, respectively), whereas the rate of TLR remained unchanged for 3 years (p = 0.15). The incidence of aneurysmal degeneration at 3 years (15.7%) did not significantly differ from that at 1 and 2 years (p = 0.69 and 0.20, respectively). CONCLUSIONS: This study highlights the favorable long-term clinical course of FP-DES in real-world practice, emphasizing the importance of monitoring for occlusive restenosis and stent thrombosis while considering the potential onset of aneurysmal degeneration.

Accuracy of maximal acceleration time of pedal arteries to diagnose critical limb-threatening ischemia.

INTRODUCTION: Maximal acceleration time of distal arteries of the foot (ATmax) is correlated to ankle-brachial index (ABI) and toe-brachial index (TBI), and seems very promising in diagnosing severe peripheral artery disease (PAD) and especially critical limb-threatening ischemia (CLTI). Our goal was to confirm the cut-off value of 215 ms to predict a toe pressure (TP) ⩽ 30 mmHg. METHODS: A 4-month retrospective study was conducted on patients addressed for suspicion of PAD. Demographic data, ABI, TBI, and Doppler ultrasound scanning parameters of the dorsal pedis and lateral plantar arteries (DPA and LPA) were recorded. RESULTS: A total of 137 patients with 258 lower limbs were included. ATmax was highly correlated to TBI (r = -0.89, p < 0.001). With the cut-off value of 215 ms, ATmax was effective to diagnose TP ⩽ 30 mmHg with a sensitivity of 93% [95% CI 77-99], a specificity of 96% [95% CI 92-98], a positive predictive value of 73% [95% CI 56-86], a negative predictive value of 99% [95% CI 97-100], and an area under the receiver operating characteristics curve of 0.99 [95% CI 0.98-1.00]. ATmax also showed promising results to rule out PAD in healthy patients. CONCLUSION: ATmax is a reliable diagnostic tool to diagnose low TP and could be a new easily performed hemodynamic criterion for diagnosis of CLTI.

Exercise therapy for chronic symptomatic peripheral artery disease.

All guidelines worldwide strongly recommend exercise as a pillar of the management of patients affected by lower extremity peripheral artery disease (PAD). Exercise therapy in this setting presents different modalities, and a structured programme provides optimal results. This clinical consensus paper is intended for clinicians to promote and assist for the set-up of comprehensive exercise programmes to best advice in patients with symptomatic chronic PAD. Different exercise training protocols specific for patients with PAD are presented. Data on patient assessment and outcome measures are narratively described based on the current best evidence. The document ends by highlighting disparities in access to supervised exercise programmes across Europe and the series of gaps for evidence requiring further research.

Comparison of the Pre-Established and Finally Selected Treatment Strategies for Endovascular Treatment in Femoropopliteal Artery Lesions.

This study aimed to compare lower limb events associated with preplanned and finally selected treatment strategies-the validity and usefulness of the physician-chosen strategy were verified.We examined the data of 1003 patients in the registry of multicenter endovascular treatment for superficial femoral and popliteal artery disease study and prospectively enrolled patients who underwent endovascular treatment (EVT) of the femoropopliteal (FP) artery between February 2017 and June 2018 from 67 Japanese institutes. The outcome measures were major adverse limb events (MALE) and target vessel revascularization.The EVT strategies were classified into balloon angioplasty-alone (37.3%), primary stenting (26.7%), and provisional stenting (36.0%) groups. In the initial strategy analysis for the balloon angioplasty-alone, primary stenting, and provisional stenting groups, two-year rates of freedom from MALE (95% confidence interval) were 0.680 (0.620-0.732), 0.754 (0.688-0.808), and 0.798 (0.746-0.840), respectively. Additionally, the rate of MALE was significantly higher among patients in the balloon angioplasty-alone group than among those in the primary or provisional stenting groups in the initial strategy analysis (P = 0.007). Changes in treatment strategy were more frequent in the primary stenting group than in the other groups. Furthermore, the rate of MALE did not significantly differ among the three groups in the final strategy analysis (P = 0.56).Limb outcomes for the final applied strategy did not differ among the three strategies. Additionally, the physician's selection bias was mostly appropriate in the EVT of the FP artery.

Intraluminal vs Subintimal Drug-Coated Balloon Angioplasty for the Treatment of Femoropopliteal Chronic Total Occlusions.

BACKGROUND: Whether intraluminal drug-coated balloon (DCB) angioplasty is superior to subintimal DCB angioplasty regarding femoropopliteal (FP) chronic total occlusion (CTO) outcomes has not been systematically determined. OBJECTIVES: The aim of this study was to compare the 1-year clinical outcomes of intraluminal and subintimal DCB angioplasty for the treatment of patients with symptomatic FP CTO. METHODS: This subanalysis of POPCORN (Prospective Multi-Center Registry of Drug-Coated Balloon for Femoropopliteal Disease) evaluated 469 lesions in 469 symptomatic patients with lower extremity artery disease who presented with FP CTO and underwent DCB treatment. Wire passage (intraluminal vs subintimal) was evaluated using intravascular ultrasound. The outcome measure, 1-year freedom from restenosis, was compared between subintimal and intraluminal DCB angioplasty groups after propensity score matching analysis. The Institutional Review Boards of participating centers approved this study. Informed consent was obtained from the participants or their families. RESULTS: During the median follow-up period of 14.2 months, restenosis occurred in 140 patients. After propensity score matching, the subintimal group had a significantly lower 1-year rate of freedom from restenosis than the intraluminal group (77.0% vs 84.2%, respectively; P = 0.024). Interaction analysis revealed a more marked increased risk for restenosis in the subintimal DCB angioplasty group in patients with severe calcification, low-dose DCB use, or smoking. CONCLUSIONS: The present study revealed that intraluminal DCB angioplasty was superior to subintimal DCB angioplasty for FP CTO treatment, with a significantly better 1-year rate of freedom from restenosis.