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.

Exercise Therapy for Chronic Symptomatic Peripheral Artery Disease: A Clinical Consensus Document of the European Society of Cardiology Working Group on Aorta and Peripheral Vascular Diseases in Collaboration With the European Society of Vascular Medicine and the European Society for Vascular Surgery.

All guidelines worldwide strongly recommend exercise as a pillar in 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 to promote and assist the set up of comprehensive exercise programmes and best advice for patients with symptomatic chronic PAD. Different exercise training protocols specific for patients with PAD are presented. Data on patient assessment and outcome measures are described based on the current best evidence. The document ends by highlighting supervised exercise programme access disparities across Europe and the evidence gaps requiring further research.

Exercise therapy for chronic symptomatic peripheral artery disease.

All guidelines worldwide strongly recommend exercise as a pillar in 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 to promote and assist the set up of comprehensive exercise programmes and best advice for patients with symptomatic chronic PAD. Different exercise training protocols specific for patients with PAD are presented. Data on patient assessment and outcome measures are described based on the current best evidence. The document ends by highlighting supervised exercise programme access disparities across Europe and the evidence gaps requiring further research.

Rivaroxaban in patients with symptomatic peripheral artery disease after lower extremity bypass surgery with venous and prosthetic conduits.

BACKGROUND: Patients with peripheral artery disease (PAD) requiring lower extremity revascularization (LER) have a high risk of adverse limb and cardiovascular events. The results from 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 have demonstrated that rivaroxaban significantly reduced this risk with an overall favorable net benefit for patients undergoing surgical revascularization. However, the efficacy and safety for those treated by surgical bypass, including stratification by bypass conduit (venous or prosthetic), has not yet been described. METHODS: In the VOYAGER PAD trial, patients who had undergone surgical and endovascular infrainguinal LER to treat PAD were randomized to rivaroxaban 2.5 mg twice daily or placebo on top of background antiplatelet therapy (aspirin 100 mg to be used in all and clopidogrel in some at the treating physician's discretion) and followed up for a median of 28 months. The primary end point was a composite of acute limb ischemia, major amputation of vascular etiology, myocardial infarction, ischemic stroke, and cardiovascular death. The principal safety outcome was major bleeding using the TIMI (thrombolysis in myocardial infarction) scale. The index procedure details, including conduit type (venous vs prosthetic), were collected at baseline. RESULTS: Among 6564 randomized patients, 2185 (33%) had undergone surgical LER. Of these 2185 patients, surgical bypass had been performed for 1448 (66%), using a prosthetic conduit for 773 patients (53%) and venous conduit for 646 patients (45%). Adjusting for the baseline differences and anatomic factors, the risk of unplanned limb revascularization in the placebo arm was 2.5-fold higher for those receiving a prosthetic conduit vs a venous conduit (adjusted hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.65-3.90; P < .001), and the risk of acute limb ischemia was three times greater (adjusted HR, 3.07; 95% CI, 1.84-5.11; P < .001). The use of rivaroxaban reduced the primary outcome for the patients treated with bypass surgery (HR, 0.78; 95% CI, 0.62-0.98), with consistent benefits for those receiving venous (HR, 0.66; 95% CI, 0.49-0.96) and prosthetic (HR, 0.87; 95% CI, 0.66-1.15) conduits (Pinteraction = .254). In the overall trial, major bleeding using the TIMI scale was increased with rivaroxaban. However, the numbers for those treated with bypass surgery were low (five with rivaroxaban vs nine with placebo; HR, 0.55; 95% CI, 0.18-1.65) and not powered to show statistical significance. CONCLUSIONS: Surgical bypass with a prosthetic conduit was associated with significantly higher rates of major adverse limb events relative to venous conduits even after adjustment for patient and anatomic characteristics. Adding rivaroxaban 2.5 mg twice daily to aspirin or dual antiplatelet therapy significantly reduced this risk, with an increase in the bleeding risk, but had a favorable benefit risk for patients treated with bypass surgery, regardless of conduit type. Rivaroxaban should be considered after lower extremity bypass for symptomatic PAD to reduce ischemic complications of the heart, limb, and brain.

Reduction in Acute Limb Ischemia With Rivaroxaban Versus Placebo in Peripheral Artery Disease After Lower Extremity Revascularization: Insights From VOYAGER PAD.

BACKGROUND: Patients with peripheral artery disease (PAD) are at heightened risk of acute limb ischemia (ALI), a thrombotic event associated with amputation, disability, and mortality. Previous lower extremity revascularization (LER) is associated with increased ALI risk in chronic PAD. However, the pattern of risk, clinical correlates, and outcomes after ALI early after LER are not well-studied, and effective therapies to reduce ALI post-LER are lacking. METHODS: The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD; rNCT02504216) randomized patients with PAD undergoing LER to rivaroxaban 2.5 mg twice daily or placebo on a background of low-dose aspirin. The primary outcome was a composite of ALI, major amputation of vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. ALI was prospectively ascertained and adjudicated by a blinded committee. The cumulative incidence of ALI was calculated using Kaplan-Meier estimates, and Cox proportional hazards models were used to generate hazard ratios and associated CIs. Analyses were performed as intention-to-treat. RESULTS: Among 6564 patients followed for a median of 2.3 years, 382 (5.8%) had a total of 508 ALI events. In placebo patients, the 3-year cumulative incidence of ALI was 7.8%. After multivariable modeling, previous LER, baseline ankle-brachial index <0.50, surgical LER, and longer target lesion length were associated with increased risk of ALI. Incident ALI was associated with subsequent all-cause mortality (hazard ratio [HR], 2.59 [95% CI, 1.98-3.39]) and major amputation (HR, 24.87 [95% CI, 18.68-33.12]). Rivaroxaban reduced ALI relative to placebo by 33% (absolute risk reduction, 2.6% at 3 years; HR, 0.67 [95% CI, 0.55-0.82]; P=0.0001), with benefit starting early (HR, 0.45 [95% CI, 0.24-0.85]; P=0.0068 at 30 days). Benefit was present for severe ALI (associated with death, amputation, or prolonged hospitalization and intensive care unit stay, HR, 0.58 [95% CI, 0.40-0.83]; P=0.003) and regardless of LER type (surgical versus endovascular revascularization, P interaction=0.42) or clopidogrel use (P interaction=0.59). CONCLUSIONS: After LER for symptomatic PAD, ALI is frequent, particularly early after LER, and is associated with poor prognosis. Low-dose rivaroxaban plus aspirin reduces ALI after LER, including ALI events associated with the most severe outcomes. The benefit of rivaroxaban for ALI appears early, continues over time, and is consistent regardless of revascularization approach or clopidogrel use.

Effect of Rivaroxaban and Aspirin in Patients With Peripheral Artery Disease Undergoing Surgical Revascularization: Insights From the VOYAGER PAD Trial.

BACKGROUND: Patients with peripheral artery disease requiring lower extremity revascularization (LER) are at high risk of adverse limb and cardiovascular events. The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) demonstrated that rivaroxaban significantly reduced this risk. The efficacy and safety of rivaroxaban has not been described in patients who underwent surgical LER. METHODS: The VOYAGER PAD trial randomized patients with peripheral artery disease after surgical and endovascular LER to rivaroxaban 2.5 mg twice daily plus aspirin or matching placebo plus aspirin and followed for a median of 28 months. The primary end point was a composite of acute limb ischemia, major vascular amputation, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was Thrombolysis in Myocardial Infarction major bleeding. International Society on Thrombosis and Haemostasis bleeding was a secondary safety outcome. All efficacy and safety outcomes were adjudicated by a blinded independent committee. RESULTS: Of the 6564 randomized, 2185 (33%) underwent surgical LER and 4379 (67%) endovascular. Compared with placebo, rivaroxaban reduced the primary end point consistently regardless of LER method (P-interaction, 0.43). After surgical LER, the primary efficacy outcome occurred in 199 (18.4%) patients in the rivaroxaban group and 242 (22.0%) patients in the placebo group with a cumulative incidence at 3 years of 19.7% and 23.9%, respectively (hazard ratio, 0.81 [95% CI, 0.67-0.98]; P=0.026). In the overall trial, Thrombolysis in Myocardial Infarction major bleeding and International Society on Thrombosis and Haemostasis major bleeding were increased with rivaroxaban. There was no heterogeneity for Thrombolysis in Myocardial Infarction major bleeding (P-interaction, 0.17) or International Society on Thrombosis and Haemostasis major bleeding (P-interaction, 0.73) on the basis of the LER approach. After surgical LER, the principal safety outcome occurred in 11 (1.0%) patients in the rivaroxaban group and 13 (1.2%) patients in the placebo group; 3-year cumulative incidence was 1.3% and 1.4%, respectively (hazard ratio, 0.88 [95% CI, 0.39-1.95]; P=0.75) Among surgical patients, the composite of fatal bleeding or intracranial hemorrhage (P=0.95) and postprocedural bleeding requiring intervention (P=0.93) was not significantly increased. CONCLUSIONS: The efficacy of rivaroxaban is associated with a benefit in patients who underwent surgical LER. Although bleeding was increased with rivaroxaban plus aspirin, the incidence was low, with no significant increase in fatal bleeding, intracranial hemorrhage, or postprocedural bleeds requiring intervention. Registration: URL: http://www.clinicaltrials.gov; Unique Identifier: NCT02504216.

Midterm outcomes of aneurysm repair with the Cook Zenith Alpha abdominal endovascular graft.

OBJECTIVE: Outcome reports after endovascular aneurysm repair (EVAR) using the low-profile Zenith Alpha Abdominal Endovascular grafts (Cook Medical, Bjæverskov, Denmark) are sparse. We present results from a single-center cohort treated with the Zenith Alpha, from a period where the graft was the primary EVAR device choice. The aim of the study was to evaluate short- and midterm outcomes of patients treated with the Zenith Alpha. METHODS: A retrospective single-center study was performed including all patients treated with the Zenith Alpha graft from October 1, 2015 to September 30, 2018. All patients underwent computed tomography angiography (CTA) imaging preoperatively as well as at 3 and 12 months postoperatively. Hereafter, patients were followed yearly with duplex ultrasound and clinical exams. Additional imaging was performed on indication. All CTAs were analyzed using three-dimensional reconstruction software (Aquarius, TeraRecon, Durham, NC). Data was extracted from electronic charts according to a protocol that remained unchanged until the end of the study (December 31, 2020). The following outcomes were assessed according to Society for Vascular Surgery/International Society of Cardiovascular Surgeons reporting criteria: aortic-related and all-cause mortality, reinterventions, instruction for use (IFU) violations, endoleaks (ELs), and aneurysm shrinkage. RESULTS: A total of 241 patients were treated with the Zenith Alpha, and 214 (89%) were asymptomatic repairs. Technical success was achieved in 238 patients (99%). One hundred fifty-seven patients (65%) received implantation outside IFU. The median hospital length of stay was 2 days (interquartile range, 2-3 days). The median clinical follow-up was 35.1 months (interquartile range, 28.8-47.5 months). The 4-year Kaplan-Meier estimate of freedom from reintervention was 66% (95% confidence interval, 59%-73%). The main reasons for reinterventions were iliac limb stenosis and occlusion (n = 30; 12%) and type 2 EL (n = 13; 5%). Overall, significantly more patients with grafts implanted outside distal IFU developed type 1B ELs (n = 10/11; P = .009). Aneurysm sac shrinkage was observed in 48 patients (25%) 1 year postoperatively. The Kaplan-Meier estimate of freedom from aortic-related mortality was 99% (95% confidence interval, 98%-100%) 4 years postoperatively. CONCLUSIONS: EVAR with the Zenith Alpha shows acceptable freedom from aortic-related mortality up to 4 years postoperatively. The majority of patients were treated outside IFU, and significantly more type 1B ELs appeared in this subgroup of patients. The leading cause for reintervention was impaired limb patency. The root cause for impaired limb patency requires further investigation.

Echolucent Carotid Plaques Becomes More Echogenic over Time - A 3D Ultrasound Study.

BACKGROUND: Despite the presence of only a few established risk factors, some patients will experience atherosclerotic events. Therefore, methods for improved risk stratification for atherosclerotic events are wanted. We aimed to detect changes in carotid artery atherosclerotic plaque volume and echogenicity over time in patients with an acute thromboembolic event and in patients with chronic atherosclerotic disease, both treated with statin, using a novel 3D ultrasound system. METHODS: We included two cohorts of patients; 70 patients, naïve to statin treatment, admitted with acute, first-time myocardial infarction (aMI), and 69 patients who had been on statin treatment for a minimum of 6 months with chronic peripheral arterial disease (cPAD). 3D ultrasound examination was performed at baseline and after 3 and 12 months. Plaque volume was quantified in 3D ultrasound plaque acquisitions, and echogenicity was assessed using grayscale median (GSM) and normalized with adventitia as reference. RESULTS: The aMI group had darker plaques than the cPAD group at baseline (mean GSM: 60.98, standard deviation (SD): 24.09 vs. 71.75, SD: 21.55; P = 0.006), 3 months (63.64, SD: 20.47 vs. 73.44, SD: 20.46; P = 0.006) and at 12 months follow-up (59.25, SD: 18.07 vs. 71.02, SD: 22.31; P = 0.004). The differences were not significant after adjusting for traditional risk factors. Dividing both groups by the median GSM, the darkest half of the aMI group's had an increase in GSM mainly within the first 3 months (10.49, CI 95%: 2.45 to 18.53; P = 0.012) and hereafter remained unchanged at 12 months follow-up (-0.53, CI 95%: -7.28 to 6.22, P = 0.875). In the darkest cPAD group GSM also increased within 3 months (8.14, CI 95%: 1.85-14.32, P = 0.012) and hereafter stabilized till 12 months (-2.54, CI 95%: -9.62 to 4.53, P = 0.475). Plaque volume did not change in the aMI group from baseline (median: 55.41 mm3, interquartile range (IQR): 24.24-84.31) to 12 months (58.67 mm3, IQR: 31.81-93.51) (P = 0.220) whereas there was a small decrease in the cPAD group from baseline (71.63 mm3, IQR: 40.12-135.61) to 12 months (67.73 mm3, IQR: 31.00-122.38) (P = 0.026). CONCLUSIONS: Echolucent carotid plaque, assessed with the novel 3D matrix ultrasound system, had increasing GSM within 3 months period, indicating stabilization of the more vulnerable plaques in aMI and cPAD patients. Plaque volume decreased over 12 months follow-up in a long-term statin-treated patient with cPAD, but not during the first 12 months statin therapy in patients with aMI.

Cancer should not contravene the revascularization of chronic limb-threatening ischaemia.

OBJECTIVES: This study aimed to examine the frequency of cancer among patients with chronic limb-threatening ischaemia (CLTI) due to peripheral artery disease (PAD) and to determine how active cancer affected outcomes after open or endovascular revascularization. In addition, we aimed to investigate all-cause mortality and cause of death in the PAD population. DESIGN: Observational single-centre cohort study based on a retrospective analysis of prospectively entered registry data. MATERIALS: All consecutive patients treated for CLTI due to PAD at a single university centre between the 1st of January 2011 and the 31st of December 2015 were included. Data from the Danish Vascular Registry (Karbase) regarding demographics, surgical procedure, and complications were linked with data from the Danish Cancer Registry and Cause of Death Registry. METHODS: The primary endpoint was major amputation-free survival. Secondary endpoints were postoperative complications within 30 days, cancer-free survival, all-cause mortality and cause of death in the cohort. Major amputation-free survival, cancer-free survival and mortality were described with Kaplan-Meier (KM) survival estimates. RESULTS: We included 920 patients, of which 116 (13%) were in the active cancer group at the time of revascularization. There was no difference in amputation-free survival between those with cancer (86.8% 1-year KM estimate) and those without cancer (85.2% 1-year KM estimate) (p = 0.50). Likewise, we found no difference in 30-day postoperative complication rate. The risk of developing cancer in the included CLTI cohort was similar to the age-matched background population (6.1% vs 6.4%) (p = 0.69). All-cause mortality was higher in CLTI patients with cancer, mainly due to cancer, compared with CLTI patients without cancer who mainly died from cardiovascular disease. Three-year KM survival estimates were 48.3% (95% CI 40.0%-58.3%) and 64.4% (95% CI 61.2%-67.8%) (p = 0.014) for cancer and non-cancer patients, respectively. CONCLUSIONS: Although cancer in patients with CLTI is related to higher medium- to long-term mortality, active cancer per se should not contravene revascularization, as postoperative complications and risk of amputation are not overrepresented.

Antithrombotic therapies in aortic and peripheral arterial diseases in 2021: a consensus document from the ESC working group on aorta and peripheral vascular diseases, the ESC working group on thrombosis, and the ESC working group on cardiovascular pharmacotherapy.

The aim of this collaborative document is to provide an update for clinicians on best antithrombotic strategies in patients with aortic and/or peripheral arterial diseases. Antithrombotic therapy is a pillar of optimal medical treatment for these patients at very high cardiovascular risk. While the number of trials on antithrombotic therapies in patients with aortic or peripheral arterial diseases is substantially smaller than for those with coronary artery disease, recent evidence deserves to be incorporated into clinical practice. In the absence of specific indications for chronic oral anticoagulation due to concomitant cardiovascular disease, a single antiplatelet agent is the basis for long-term antithrombotic treatment in patients with aortic or peripheral arterial diseases. Its association with another antiplatelet agent or low-dose anticoagulants will be discussed, based on patient's ischaemic and bleeding risk as well therapeutic paths (e.g. endovascular therapy). This consensus document aims to provide a guidance for antithrombotic therapy according to arterial disease localizations and clinical presentation. However, it cannot substitute multidisciplinary team discussions, which are particularly important in patients with uncertain ischaemic/bleeding balance. Importantly, since this balance evolves over time in an individual patient, a regular reassessment of the antithrombotic therapy is of paramount importance.

Rivaroxaban and Aspirin in Peripheral Artery Disease Lower Extremity Revascularization: Impact of Concomitant Clopidogrel on Efficacy and Safety.

BACKGROUND: The VOYAGER PAD trial (Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) demonstrated superiority of rivaroxaban plus aspirin versus aspirin to reduce major cardiac and ischemic limb events after lower extremity revascularization. Clopidogrel is commonly used as a short-term adjunct to aspirin after endovascular revascularization. Whether clopidogrel modifies the efficacy and safety of rivaroxaban has not been described. METHODS: VOYAGER PAD was a phase 3, international, double-blind, placebo-controlled trial in patients with symptomatic PAD undergoing lower extremity revascularization randomized to rivaroxaban 2.5 mg twice daily plus 100 mg aspirin daily or rivaroxaban placebo plus aspirin. The primary efficacy outcome was a composite of acute limb ischemia, major amputation of a vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety end point was TIMI (Thrombolysis in Myocardial Infarction) major bleeding, with International Society on Thrombosis and Haemostasis major bleeding a secondary safety outcome. Clopidogrel use was allowed at the discretion of the investigator for up to 6 months after the qualifying revascularization. RESULTS: Of the randomized patients, 3313 (50.6%) received clopidogrel for a median duration of 29.0 days. Over 3 years, the hazard ratio for the primary outcome of rivaroxaban versus placebo was 0.85 (95% CI, 0.71-1.01) with clopidogrel and 0.86 (95% CI, 0.73-1.01) without clopidogrel without statistical heterogeneity (P for interaction=0.92). Rivaroxaban resulted in an early apparent reduction in acute limb ischemia within 30 days (hazard ratio, 0.45 [95% CI, 0.14-1.46] with clopidogrel; hazard ratio, 0.48 [95% CI, 0.22-1.01] without clopidogrel; P for interaction=0.93). Compared with aspirin, rivaroxaban increased TIMI major bleeding similarly regardless of clopidogrel use (P for interaction=0.71). With clopidogrel use >30 days, rivaroxaban was associated with more International Society on Thrombosis and Haemostasis major bleeding within 365 days (hazard ratio, 3.20 [95% CI, 1.44-7.13]) compared with shorter durations of clopidogrel (P for trend=0.06). CONCLUSIONS: In the VOYAGER PAD trial, rivaroxaban plus aspirin reduced the risk of adverse cardiovascular and limb events with an early benefit for acute limb ischemia regardless of clopidogrel use. The safety of rivaroxaban was consistent regardless of clopidogrel use but with a trend for more International Society on Thrombosis and Haemostasis major bleeding with clopidogrel use >30 days than with a shorter duration. These data support the addition of rivaroxaban to aspirin after lower extremity revascularization regardless of concomitant clopidogrel, with a short course (≤30 days) associated with less bleeding. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02504216.

Three-dimensional ultrasound improves identification of patients with abdominal aortic aneurysms reaching the threshold for repair.

OBJECTIVE: Conventional two-dimensional ultrasound (2D-US) has been the recommended and preferred modality for the diagnosis and surveillance of abdominal aortic aneurysms (AAAs). Measurement of the aneurysm diameter using three-dimensional ultrasound (3D-US) has shown promising results in a research setting, improving agreement and reproducibility. However, studies evaluating 3D-US in a clinical context are lacking, which could hinder the optimal usage of this new modality. In the present study, we investigated the clinical value of 3D-US for AAA surveillance compared with the current standard 2D-US examination. METHODS: Data from 126 patients with infrarenal AAAs <50 mm and 55 mm (female and male, respectively) were available for analysis. Eligibility was determined using the standard 2D-US anteroposterior (AP) diameter with a dual-plane technique. All the patients had subsequently undergone additional 3D-US and computed tomography angiography (CTA). Using CTA as the reference standard, the maximal standard 2D-US AP diameter was compared with that from 3D-US. RESULTS: All 126 AAAs were, per the inclusion criteria, small, with no intervention indicated. With the addition of 3D-US imaging to the 2D-US-based surveillance program, the AAA diameter threshold (50 and 55 mm) was exceeded for 31 of the 126 patients (25%). These 31 patients were withdrawn from the present study and referred for treatment planning. Compared with the CTA AP diameter (mean, 49 ± 7.2 mm), the mean 3D-US AP diameter (mean, 49 ± 6.7 mm) was significantly more accurate than the standard mean 2D-US AP diameter (45 ± 6.2 mm; kappa value, 0.86 ± 0.05; 95% confidence interval, 0.76-0.96; kappa value, 0.01 ± 0.04; 95% confidence interval, -0.05 to 0.09, respectively). CONCLUSIONS: For clinical use, the AAA diameter assessment using 3D-US was significantly more accurate than that with 2D-US and can substantially change the clinical management, from surveillance to operative treatment, for approximately one fourth of patients with an AAA. Further studies evaluating the clinical consequences of the 2D to 3D paradigm shift in AAA diagnostics are warranted, including sensitivity, specificity, agreement, and reproducibility estimation.

Three-dimensional ultrasound is a reliable alternative in endovascular aortic repair surveillance.

OBJECTIVE: Three-dimensional ultrasound (3D-US) has already demonstrated improved reproducibility with a high degree of agreement (intermodality variability), reproducibility (interoperator variability), and repeatability (intraoperator variability) compared with conventional two-dimensional ultrasound (2D-US) when estimating the maximum diameter of native abdominal aortic aneurysms (AAAs). The aim of the present study was, in a clinical, multicenter setting, to evaluate the accuracy of 3D-US with aneurysm model quantification software (3D-US abdominal aortic aneurysm [AAA] model) for endovascular aortic aneurysm repair (EVAR) sac diameter assessment vs that of computed tomography angiography (CTA) and 2D-US. METHODS: A total of 182 patients who had undergone EVAR from April 2016 to December 2017 and were compliant with a standardized EVAR surveillance program were enrolled from five different vascular centers (Rigshospitalet, Copenhagen, Denmark; Catharina Ziekenhuis, Eindhoven, Netherlands; L'hospital de la Timone, Paris, France; Cleveland Clinic, Cleveland, Ohio; and The Christ Hospital, Cincinnati, Ohio) in four countries. All image acquisitions were performed at the local sites (ie, 2D-US, 3D-US, CTA). Only the 2D-US and CTA readings were performed both locally and centrally. All images were read centrally by the US and CTA core laboratory. Anonymized image data were read in a randomized and blinded manner. RESULTS: The sample used to estimate the accuracy of the 3D-US AAA model and 2D-US included 164 patients and 177 patients, respectively. The Bland-Altman analysis revealed that the mean difference between CTA and 3D-US was -2.43 mm (95% confidence interval [CI], -5.20 to 0.14; P = .07) with a lower and upper limit of agreement of -8.9 mm (95% CI, -9.3 to -8.4) and 2.7 mm (95% CI, 2.3-3.2), respectively. For 2D-US and CTA, the mean difference was -3.62 mm (95% CI, -6.14 to -1.10; P = .002), with a lower and upper limit of agreement of -10.3 mm (95% CI, -10.8 to -9.8) and 2.5 mm (95% CI, 2-2.9), respectively. CONCLUSIONS: The 3D-US AAA model showed no significant difference compared with CTA for measuring the anteroposterior diameter, indicating less bias for 3D-US compared with 2D-US. Thus, 3D-US with AAA model software is a viable modality for anteroposterior diameter assessment for surveillance after EVAR.

Cardiovascular Rehabilitation Increases Walking Distance in Patients With Intermittent Claudication. Results of the CIPIC Rehab Study: A Randomised Controlled Trial.

OBJECTIVE: To examine whether a cardiac rehabilitation programme in a community based setting for patients with intermittent claudication (IC) affects walking ability, quality of life, and changes in health behaviour. The trial investigated a cross sector cardiovascular rehabilitation programme compared with usual care for patients having non-operative management. METHODS: The trial allocated 118 patients, with 1:1 individual randomisation to either an intervention or control group. Data were collected at a department of vascular surgery and at a healthcare centre in Denmark. The rehabilitation intervention consisted of usual care plus 12 weeks of exercise training, pedometer, health education, and text messages. The primary outcome was maximum walking distance at six months measured by treadmill walking test. The secondary outcomes were maximum walking distance at 12 months and pain free walking distance measured by treadmill walking test, healthy diet, level of physical activity, and quality of life (QoL) at six and 12 months. RESULTS: In the intervention group, 46 participants were analysed, with 47 in the control group. Following three months of rehabilitation, a 37% difference (95% CI 1.10 - 1.70; p = .005) was found between groups in maximum walking distance at six and 12 months, in favour of the intervention group. The same positive effect was found in physical activity, QoL, and healthy diet, but was not statistically significant in pain free walking distance and smoking. CONCLUSION: A specialised community based cardiac rehabilitation programme for patients with IC showed statistically and clinically significant effects on maximum walking distance, physical activity, quality of life, and healthy diet, but not on pain free walking distance and smoking, compared with usual care without rehabilitation.

Endovascular Treatment of Chronic and Acute on Chronic Mesenteric Ischaemia: Results From a National Cohort of 245 Cases.

OBJECTIVE: Endovascular treatment of chronic mesenteric ischaemia (CMI) is linked to low early morbidity and mortality but a higher risk of recurrence than open repair. Mid and long term outcomes after endovascular treatment remain to be proven in larger series. The aim of this study was to assess short and mid term outcome after first line endovascular revascularisation of CMI and acute on chronic mesenteric ischaemia (AoCMI). METHODS: This was a prospective population and registry based cohort study supplemented by a retrospective review of medical records and imaging files. A national cohort was created based on data extracted from the Danish National Registry for Vascular Surgery (Karbase) for all patients treated endovascularly for CMI or AoCMI between 2011 and 2015 in Denmark. Survival data, bowel resection, complications, re-intervention rate, and improvement of clinical symptoms were analysed, as were potential risk factors. RESULTS: In total, 245 patients had an endovascular intervention for CMI (n = 178; 72.6%) and AoCMI (n = 67; 27.3%). One and three year survival estimates were 85% (95% confidence interval [CI] 79 - 90) and 74% (95% CI 67 - 80) in the CMI-group, and 67% (95% CI 54 - 77) and 54% (95% CI 41 - 65) in the AoCMI group. The hazard ratio for death was 1.89 (95% CI 1.23 - 2.9) for AoCMI, relative to patients with CMI. Superior mesenteric artery (SMA) stenosis, rather then occlusion, significantly increased the success of SMA recanalisation: OR 19.4 (95% CI 6.2 - 61.4) and 9.3 (95% CI 1.6 - 53.6) in the CMI and AoCMI groups, respectively. The proportion of patients reporting clinical improvement was 71% (n = 127) in the CMI group and 59% (n = 39) in the AoCMI group. Five patients (3%) in the CMI and 30 (45%) in the AoCMI groups underwent bowel resection (p < .001), and the overall length of hospital stay (LoS) was a median of two days (interquartile range [IQR] 1 - 3 days) in the CMI group and seven days (IQR 3 - 23 days) in the AoCMI group. Within the first year, re-intervention was performed in 14 patients (5.7%). CONCLUSION: First line endovascular treatment of CMI carries a three year mortality rate of 25%, and low risk of re-occurrence of symptomatic ischaemia. Relative to CMI, patients suffering AoCMI have significantly higher morbidity and mortality, more bowel resections, and longer LoS.

Low Risk of Neurological Recurrence while Awaiting Carotid Endarterectomy: Results From a Danish Multicentre Study.

OBJECTIVE: The risk of ipsilateral neurological recurrence (NR) was assessed in patients awaiting carotid endarterectomy (CEA) due to symptomatic carotid artery stenosis and whether current national guidelines of performing CEA within 14 days are adequate in present day practice. METHODS: This was a retrospective multicentre observational cohort study. Patients scheduled for CEA due to symptomatic carotid artery stenosis in a five year period, 1 January 2014 to 31 December 2018, from four centres were included. Data from the Danish Vascular Registry (www.karbase.dk), operative managing systems, and electronic medical records were reviewed. RESULTS: In total, 1 125 patients scheduled for CEA were included and 1 095 (97%) underwent the planned surgery. During a median delay from index event to CEA of 11 days (interquartile range 8-16 days), 40 patients (3.6%; 95% confidence interval [CI] 2.5%-5%) experienced a NR. One third were minor strokes (n = 12, 30%); half were transient ischaemic attacks (TIA) (n = 22, 55%); and amaurosis fugax accounted for 15% (n = 6). Twenty-six (2%) CEA procedures was cancelled, of which one was due to a disabling recurrent ischaemic event (aphasia). There were no deaths or major strokes in the waiting time for CEA. Best medical treatment (BMT) with platelet inhibitory or anticoagulation drugs and a statin was initiated in nearly all patients (98%) at first assessment. The overall 30 day risk of a post-operative major event (death or stroke) was (Kaplan-Meier [KM] estimate) 2.7% (95% CI 1.8-3.8), and not significantly correlated with the timing of surgery. Most (69%) occurred within the first three days. One, two, and three year mortality rate for CEA patients was (KM estimate) 4.8%, 7.8%, and 11.5% respectively. CONCLUSION: In symptomatic carotid artery stenosis patients awaiting CEA, very few NRs occurred within 14 days. Institution of immediate BMT in specialised TIA/stroke units followed by early, but not necessarily urgent, CEA is a reasonable course of action in patients with high grade symptomatic carotid artery stenosis.

Three- and Two-Dimensional Ultrasound is as Accurate as Computed Tomography in Aortic Sac Assessment after Endovascular Aortic Repair.

BACKGROUND: To compare aortic sac changes after endovascular aneurysm repair (EVAR) assessed by three-dimensional ultrasound (3D-US), two-dimensional ultrasound (2D-US), and traditional computed tomographic angiography (CTA). METHODS: Using volume assessment with three-dimensional CTA (3D-CTA-volume) as the gold standard, this study investigated aortic sac changes at three and 12 months after EVAR with three different ultrasound methods (2D-US anterior-posterior (AP) diameter, 3D-US AP centerline diameter, and 3D-US partial volume), and traditional CT multiplanar outer-to-outer diameter (CT-MPR OTO diameter). From august 1st, 2011 to January 2014, consecutive EVAR patients (n = 113) were available for analysis in two time intervals; 1) between preoperative and three-month follow-up and 2) between three and 12 month follow-up. RESULTS: The risk of missing true aortic sac growth (false negative finding) at three-month postoperative visit using 3D-US partial volume, 3D-US AP centerline diameter, 2D-US AP diameter, and CT-MPR OTO diameter was 19%, 21%, 22%, and 18%, respectively. Corresponding low sensitivities (0% to 21%) and kappa-values (<0.50) in detecting aortic sac changes were found. The risk of missing true growth between three and 12 months were lower (6%, 5%, 6%, and 6%, respectively), and matching sensitivities 33%, 33%, 17%, and 17%, respectively. CONCLUSIONS: All tested methods for aortic sac changes were as good as traditional CT-MPR OTO diameter and corresponded poorly with 3D-CTA-volume at three months postoperative visit but substantially better after 12 months where the residual sac change was more profound.

The Short-term Predictive Value of Vessel Wall Stiffness on Abdominal Aortic Aneurysm Growth.

BACKGROUND: Abdominal aortic aneurysm (AAA) surveillance programs are currently based solely on AAA diameter. The diameter criterion alone, however, seems inadequate as small AAAs comprise 5-10 % of ruptured AAAs as well as some large AAAs never rupture. Aneurysm wall stiffness has been suggested to predict rupture and growth; this study aimed to investigate the prognostic value of AAA vessel wall stiffness for growth on prospectively collected data. METHODS: Analysis was based on data from a randomised, placebo-controlled, multicentre trial investigating mast-cell-inhibitors to halt aneurysm growth (the AORTA trial). Systolic and diastolic AAA diameter was determined in 326 patients using electrocardiogram-gated ultrasound (US). Stiffness was calculated at baseline and after 1 year. RESULTS: Maximum AAA diameter increased from 44.1 mm to 46.5 mm during the study period. Aneurysm growth after 1 year was not predicted by baseline stiffness (-0.003 mm/U; 95 % CI: -0.007 to 0.001 mm/U; P = 0.15). Throughout the study period, stiffness remained unchanged (8.3 U; 95 % CI: -2.5 to 19.1 U; P = 0.13) and without significant correlation to aneurysm growth (R: 0.053; P = 0.38). CONCLUSIONS: Following a rigorous US protocol, this study could not confirm AAA vessel wall stiffness as a predictor of aneurysm growth in a 1-year follow-up design. The need for new and subtle methods to complement diameter for improved AAA risk assessment is warranted.

International public awareness of peripheral artery disease.

Background: Peripheral artery disease (PAD) of the lower limbs is a common condition with considerable global burden. Some country-specific studies suggest low levels of public awareness. To our knowledge public awareness of PAD has never been assessed simultaneously in several countries worldwide. Patients and methods: This was an international, general public, internet-based quantitative survey assessing vascular health and disease understanding. Questionnaires included 23 closed-ended multiple-choice, Likert scale and binary choice questions. Data were collected from 9,098 survey respondents from nine countries in Europe, North and Latin America during May-June 2018. Results: Overall, familiarity with PAD was low (57% of respondents were "not at all familiar", and 9% were "moderately" or "very familiar"). Knowledge about PAD health consequences was limited, with 55% of all respondents not being aware of limb consequences of PAD. There were disparities in PAD familiarity levels between countries; highest levels of self-reported awareness were in Germany and Poland where 13% reported to be "very" or "moderately" familiar with PAD, and lowest in Scandinavian countries (5%, 3% and 2% of respondents in Norway, Sweden and Denmark, respectively). There were disparities in awareness according to age. Respondents aged 25-34 were most familiar with PAD, with 12% stating that they were "moderately" or "very" familiar with the condition, whereas those aged 18-24 were the least familiar with PAD (7% "moderately" or "very" familiar with PAD). In the 45-54, 55-64 and 65+ age groups, 9% said they were "moderately" or "very" familiar with the term. There was no important gender-based difference in PAD familiarity. Conclusions: On an international level, public self-reported PAD awareness is low, even though PAD is a common condition with considerable burden. Campaigns to increase PAD awareness are needed to reduce delays in diagnosis and to motivate people to control PAD risk factors.

Clinical validation of three-dimensional ultrasound for abdominal aortic aneurysm.

OBJECTIVE: Three-dimensional ultrasound (3D-US) examination is a relatively new modality that can be used for abdominal aortic aneurysm (AAA) surveillance, and may offer improved reproducibility over conventional two-dimensional ultrasound (2D-US) examination. The aim of this study was to evaluate the interoperator reproducibility of maximum anterior-to-posterior diameter by nonphysician ultrasound technicians in a typical vascular laboratory setting, on patients with infrarenal AAAs using 3D-US and 2D-US examination. METHODS: A total of 134 consecutive patients with asymptomatic infrarenal AAAs were screened. Of the 134 patients, 28 (21%) were screen failures. From the remaining 106 patients, 3 (2.8%) had missing data and 13 (12.3%) had technically unacceptable image quality. As a result, 90 patients were included for final analysis. Ultrasound image acquisitions were performed during the single visit. The 2D-US images were evaluated at the time of examination by the respective ultrasound technicians who acquired them. All 3D-US images were evaluated offline by both ultrasound technicians after a wash-out period of at least 6 weeks. RESULTS: Excellent interoperator reproducibility was observed for measuring maximum diameter using 3D-US (intraclass correlation coefficient, 0.97), and good agreement among ultrasound technicians (mean difference, -0.08 mm; limits of agreement, -3.17; 3.00 mm). When using 3D-US examination, 74 of the 90 patients (82%) were estimated within 2 mm of interoperator variability. Of 90 patients, 52 (58%) were estimated to be within the same variability by 2D-US examination. Estimating AAA diameter using 3D-US was superior to 2D-US with respect to interoperator reproducibility. CONCLUSIONS: Both 3D-US and 2D-US examination demonstrated good reproducibility among two vascular ultrasound technicians with superior agreement from 3D-US examination. The present results support the broader use of 3D-US in standard AAA surveillance programs.