Effect of a Home-Based Exercise Intervention of Wearable Technology and Telephone Coaching on Walking Performance in Peripheral Artery Disease: The HONOR Randomized Clinical Trial.

Importance: Clinical practice guidelines support home-based exercise for patients with peripheral artery disease (PAD), but no randomized trials have tested whether an exercise intervention without periodic medical center visits improves walking performance. Objective: To determine whether a home-based exercise intervention consisting of a wearable activity monitor and telephone coaching improves walking ability over 9 months in patients with PAD. Design, Setting, and Participants: Randomized clinical trial conducted at 3 US medical centers. Patients with PAD were randomized between June 18, 2015, and April 4, 2017, to home-based exercise vs usual care for 9 months. Final follow-up was on December 5, 2017. Interventions: The exercise intervention group (n = 99) received 4 weekly medical center visits during the first month followed by 8 months of a wearable activity monitor and telephone coaching. The usual care group (n = 101) received no onsite sessions, active exercise, or coaching intervention. Main Outcomes and Measures: The primary outcome was change in 6-minute walk distance at 9-month follow-up (minimal clinically important difference [MCID], 20 m). Secondary outcomes included 9-month change in subcomponents of the Walking Impairment Questionnaire (WIQ) (0-100 score; 100, best), SF-36 physical functioning score, Patient-Reported Outcomes Measurement Information System (PROMIS) mobility questionnaire (higher = better; MCID, 2 points), PROMIS satisfaction with social roles questionnaire, PROMIS pain interference questionnaire (lower = better; MCID range, 3.5-4.5 points), and objectively measured physical activity. Results: Among 200 randomized participants (mean [SD] age, 70.2 [10.4] years; 105 [52.5%] women), 182 (91%) completed 9-month follow-up. The mean change from baseline to 9-month follow-up in the 6-minute walk distance was 5.5 m in the intervention group vs 14.4 m in the usual care group (difference, -8.9 m; 95% CI, -26.0 to 8.2 m; P = .31). The exercise intervention worsened the PROMIS pain interference score, mean change from baseline to 9 months was 0.7 in the intervention group vs -2.8 in the usual care group (difference, 3.5; 95% CI, 1.3 to 5.8; P = .002). There were no significant between-group differences in the WIQ score, the SF-36 physical functioning score, or the PROMIS mobility or satisfaction with social roles scores. Conclusions and Relevance: Among patients with PAD, a home-based exercise intervention consisting of a wearable activity monitor and telephone coaching, compared with usual care, did not improve walking performance at 9-month follow-up. These results do not support home-based exercise interventions of wearable devices and telephone counseling without periodic onsite visits to improve walking performance in patients with PAD. Trial Registration: clinicaltrials.gov Identifier: NCT02462824.

Femoral artery plaque characteristics, lower extremity collaterals, and mobility loss in peripheral artery disease.

Little is known about the prognostic significance of specific characteristics of magnetic resonance imaging (MRI) measured plaque in the superficial femoral artery (SFA). Associations of MRI-measured plaque quantity, lumen area, and plaque composition in the SFA with subsequent mobility loss were studied in people with lower extremity peripheral artery disease (PAD). Participants with an ankle-brachial index (ABI) < 1.00 were identified from Chicago medical centers and underwent direct visualization of atherosclerotic plaque in the SFA using MRI. Participants were followed annually for up to 4 years. Mobility loss was defined as becoming unable to walk up and down a flight of stairs or walk one-quarter of a mile without assistance among participants without mobility impairment at baseline. Analyses adjusted for age, sex, race, comorbidities, ABI, physical activity, and other confounders. Of 308 PAD participants without baseline mobility impairment, 100 (32.5%) developed mobility loss during follow-up. Compared to the lowest mean plaque area tertile at baseline, participants in the highest (worst) plaque area tertile had a higher rate of mobility loss (hazard ratio (HR) = 2.08, 95% confidence interval (CI) = 1.14-3.79, p = 0.018). Compared to the highest mean lumen area tertile, the smallest (worst) mean lumen area tertile was associated with greater mobility loss (HR = 2.18, 95% CI = 1.20-3.96, p = 0.011). Neither lipid rich necrotic core nor calcium in the SFA were associated with mobility loss. In conclusion, greater plaque quantity and smaller lumen area in the proximal SFA, but not lipid rich necrotic core or calcium, were associated with higher mobility loss in people with PAD.

Effect of Granulocyte-Macrophage Colony-Stimulating Factor With or Without Supervised Exercise on Walking Performance in Patients With Peripheral Artery Disease: The PROPEL Randomized Clinical Trial.

Importance: Benefits of granulocyte-macrophage colony-stimulating factor (GM-CSF) for improving walking ability in people with lower extremity peripheral artery disease (PAD) are unclear. Walking exercise may augment the effects of GM-CSF in PAD, since exercise-induced ischemia enhances progenitor cell release and may promote progenitor cell homing to ischemic calf muscle. Objectives: To determine whether GM-CSF combined with supervised treadmill exercise improves 6-minute walk distance, compared with exercise alone and compared with GM-CSF alone; to determine whether GM-CSF alone improves 6-minute walk more than placebo and whether exercise improves 6-minute walk more than an attention control intervention. Design, Setting, and Participants: Randomized clinical trial with 2 × 2 factorial design. Participants were identified from the Chicago metropolitan area and randomized between January 6, 2012, and December 22, 2016, to 1 of 4 groups: supervised exercise + GM-CSF (exercise + GM-CSF) (n = 53), supervised exercise + placebo (exercise alone) (n = 53), attention control + GM-CSF (GM-CSF alone) (n = 53), attention control + placebo (n = 51). The final follow-up visit was on August 15, 2017. Interventions: Supervised exercise consisted of treadmill exercise 3 times weekly for 6 months. The attention control consisted of weekly educational lectures by clinicians for 6 months. GM-CSF (250 µg/m2/d) or placebo were administered subcutaneously (double-blinded) 3 times/wk for the first 2 weeks of the intervention. Main Outcomes and Measures: The primary outcome was change in 6-minute walk distance at 12-week follow-up (minimum clinically important difference, 20 m). P values were adjusted based on the Hochberg step-up method. Results: Of 827 persons evaluated, 210 participants with PAD were randomized (mean age, 67.0 [SD, 8.6] years; 141 [67%] black, 82 [39%] women). One hundred ninety-five (93%) completed 12-week follow-up. At 12-week follow-up, exercise + GM-CSF did not significantly improve 6-minute walk distance more than exercise alone (mean difference, -6.3 m [95% CI, -30.2 to +17.6]; P = .61) or more than GM-CSF alone (mean difference, +28.7 m [95% CI, +5.1 to +52.3]; Hochberg-adjusted P = .052). GM-CSF alone did not improve 6-minute walk more than attention control + placebo (mean difference, -1.4 m [95% CI, -25.2 to +22.4]; P = .91). Exercise alone improved 6-minute walk compared with attention control + placebo (mean difference, +33.6 m [95% CI, +9.4 to +57.7]; Hochberg-adjusted P = .02). Conclusions and Relevance: Among patients with PAD, supervised treadmill exercise significantly improved 6-minute walk distance compared with attention control + placebo, whereas GM-CSF did not significantly improve walking performance, either when used alone or when combined with supervised treadmill exercise. These results confirm the benefits of exercise but do not support using GM-CSF to treat walking impairment in patients with PAD. Trial Registration: clinicaltrials.gov Identifier: NCT01408901.

Changes in D-dimer and inflammatory biomarkers before ischemic events in patients with peripheral artery disease: The BRAVO Study.

Whether circulating biomarker levels increase shortly before an ischemic heart disease (IHD) event is unknown. We studied whether levels of D-dimer, C-reactive protein (CRP), and serum amyloid A (SAA) are higher within 2 months of an IHD event compared to time periods more than 2 months before the IHD event. We assembled 595 participants with peripheral artery disease (PAD) and followed them for up to 3 years. Blood samples were obtained every 2 months. The primary outcome was IHD events: myocardial infarctions, unstable angina, or IHD death. We used a nested case-control design. Fifty participants (cases) had events and were each matched by age, sex, duration in the study, and number of blood draws to two controls without events. Among cases, the mean D-dimer value of 1.105 obtained within 2 months of the event was higher than values obtained 10 months (0.68 mg/L, p<0.001), 12 months (0.71 mg/L, p=0.001), 16 months (0.65 mg/L, p=0.008), 20 months (p=0.032), 22 months (p=0.033), 26 months (p=0.038), and 32 months (p=0.04) before the event. Compared to controls, median D-dimer levels in cases were higher 4 months (p=0.017), 6 months (p=0.005), and 8 months (p=0.028) before the event. Values of CRP and SAA obtained within two months of an IHD event not consistently higher than values obtained during the prior months. In PAD participants with an IHD event, D-dimer was higher within 2 months of the event, compared to most values obtained 10 to 32 months previously. D-dimer was also higher in cases as compared to controls during most visits within 8 months of the IHD event.

Deep venous thrombosis after saphenous endovenous radiofrequency ablation: is it predictable?

BACKGROUND: Endovenous radiofrequency ablation (RFA) is a safe and effective treatment for varicose veins caused by saphenous reflux. Deep venous thrombosis (DVT) is a known complication of this procedure. The purpose of this study is to describe the frequency of DVT after RFA and the associated predisposing factors. METHODS: A retrospective analysis was performed using prospectively collected data from December 2008 to December 2011; a total of 277 consecutive office-based RFA procedures were performed at a single institution using the VNUS ClosureFast catheter (VNUS Medical Technologies, San Jose, CA). Duplex ultrasonography scans were completed 2 weeks postprocedure in all patients. Risk factors assessed for the development of DVT included: great versus small saphenous vein (SSV) treated, right versus left side treated, number of radiofrequency cycles used, hypercoagulable state, history of DVT, tobacco use, medications (i.e., oral contraceptives, aspirin, warfarin, and clopidogrel), and vein diameter at the junction of the superficial and deep systems. RESULTS: Seventy-two percent of the patients were women, 56% were treated on the right side, and 86% were performed on the great saphenous vein (GSV). The mean age was 54 ± 14 years (range: 23-88 years). Three percent of patients had a preprocedure diagnosis of hypercoagulable state, and 8% had a history of previous DVT. On postprocedural ultrasound, thrombus protrusion into the deep system without occlusion (endovenous heat-induced thrombosis) was present in 11 patients (4%). DVT, as defined by thrombus protrusion with complete occlusion of the femoral or popliteal vein, was identified in 2 patients (0.7%). Previous DVT was the only factor associated with postprocedural DVT (P = 0.018). Although not statistically significant, there was a trend toward a higher risk of DVT in SSV-treated patients. Factors associated with endovascular heat-induced thrombosis alone were male sex (P = 0.02), SSV treatment (P = 0.05), aspirin use (P = 0.008), and factor V Leiden deficiency (P = 0.01). CONCLUSIONS: The use of RFA to treat patients with symptoms caused by saphenous reflux involves a small but definite risk of DVT. This study shows that the risk of post-RFA DVT is greater in patients with previous DVT, with a trend toward an increased risk in patients having treatment of the SSV. Periprocedural anticoagulation may be considered in this subset to reduce the risk of DVT after RFA. Thrombus protrusion without DVT was found to be more likely in patients with hypercoagulability, male sex, SSV treatment, and aspirin use. Additional prospective studies are required to analyze these and other factors that may predict thrombotic events after endovenous RFA.

Endoleaks after endovascular abdominal aortic aneurysm repair: management strategies according to CT findings.

OBJECTIVE: With increasing use of endovascular techniques for repair of abdominal aortic aneurysms, the prevalence of leakage into excluded aneurysm sacs (endoleaks) as a complication has risen. We will describe and illustrate the imaging findings for endoleaks involving abdominal aortic aneurysms. We will also discuss which types of endoleaks require urgent catheter-based evaluation. CONCLUSION: Radiologists should be familiar with the classification scheme for endoleaks and understand which types of endoleaks require urgent catheter-based evaluation.

Treadmill exercise and resistance training in patients with peripheral arterial disease with and without intermittent claudication: a randomized controlled trial.

CONTEXT: Neither supervised treadmill exercise nor strength training for patients with peripheral arterial disease (PAD) without intermittent claudication have been established as beneficial. OBJECTIVE: To determine whether supervised treadmill exercise or lower extremity resistance training improve functional performance of patients with PAD with or without claudication. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled clinical trial performed at an urban academic medical center between April 1, 2004, and August 8, 2008, involving 156 patients with PAD who were randomly assigned to supervised treadmill exercise, to lower extremity resistance training, or to a control group. MAIN OUTCOME MEASURES: Six-minute walk performance and the short physical performance battery. Secondary outcomes were brachial artery flow-mediated dilation, treadmill walking performance, the Walking Impairment Questionnaire, and the 36-Item Short Form Health Survey physical functioning (SF-36 PF) score. RESULTS: For the 6-minute walk, those in the supervised treadmill exercise group increased their distance walked by 35.9 m (95% confidence interval [CI], 15.3-56.5 m; P < .001) compared with the control group, whereas those in the resistance training group increased their distance walked by 12.4 m (95% CI, -8.42 to 33.3 m; P = .24) compared with the control group. Neither exercise group improved its short physical performance battery scores. For brachial artery flow-mediated dilation, those in the treadmill group had a mean improvement of 1.53% (95% CI, 0.35%-2.70%; P = .02) compared with the control group. The treadmill group had greater increases in maximal treadmill walking time (3.44 minutes; 95% CI, 2.05-4.84 minutes; P < .001); walking impairment distance score (10.7; 95% CI, 1.56-19.9; P = .02); and SF-36 PF score (7.5; 95% CI, 0.00-15.0; P = .02) than the control group. The resistance training group had greater increases in maximal treadmill walking time (1.90 minutes; 95% CI, 0.49-3.31 minutes; P = .009); walking impairment scores for distance (6.92; 95% CI, 1.07-12.8; P = .02) and stair climbing (10.4; 95% CI, 0.00-20.8; P = .03); and SF-36 PF score (7.5; 95% CI, 0.0-15.0; P = .04) than the control group. CONCLUSIONS: Supervised treadmill training improved 6-minute walk performance, treadmill walking performance, brachial artery flow-mediated dilation, and quality of life but did not improve the short physical performance battery scores of PAD participants with and without intermittent claudication. Lower extremity resistance training improved functional performance measured by treadmill walking, quality of life, and stair climbing ability. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00106327.

Plaque Composition in the Proximal Superficial Femoral Artery and Peripheral Artery Disease Events.

OBJECTIVES: The aim of this study was to describe associations of the presence of lipid-rich necrotic core (LRNC) in the proximal superficial femoral artery (SFA) with lower extremity peripheral artery disease (PAD) event rates and systemic cardiovascular event rates. BACKGROUND: LRNC in the coronary and carotid arteries is associated with adverse outcomes but has not been studied previously in lower extremity arteries. METHODS: Participants with ankle-brachial index (ABI) values <1.00 were identified from Chicago medical centers and followed annually. Magnetic resonance imaging was used to characterize SFA atherosclerotic plaque at baseline. Medical records for hospitalizations and procedures after baseline were adjudicated for lower extremity revascularization, amputation, and critical limb ischemia and also for new coronary events, ischemic stroke, and mortality. RESULTS: Of 254 participants with PAD, 62 (24%) had LRNC and 149 (59%) had calcium in the SFA at baseline. Cox regression analyses were adjusted for age, sex, race, comorbidities, baseline ABI, and other confounders. SFA LRNC was associated with an increased incidence of the combined outcome of lower extremity amputation, critical limb ischemia, ABI decline >0.15, and revascularization at 47-month follow-up (hazard ratio: 2.18; 95% confidence interval: 1.27 to 3.75; p = 0.005). The association of SFA LRNC with PAD events was maintained even when this combined outcome excluded lower extremity revascularization (hazard ratio: 2.58; 95% confidence interval: 1.25 to 5.33; p = 0.01). LRNC in the SFA was not associated with all-cause mortality, acute coronary events, or stroke. CONCLUSIONS: Among patients with PAD, LRNC in the SFA was associated with higher rates of clinical PAD events, and this association was independent of ABI. Further study is needed to determine whether interventions that reduce SFA LRNC prevent PAD events.

Delayed Retrograde Ascending Aortic Dissection After Endovascular Repair of Descending Dissection.

We report the case of a 34-year-old woman who developed delayed retrograde ascending aortic dissection after previous endovascular repair of her descending thoracic aorta. Preoperative computed tomography imaging specifically highlights the interaction of endograft springs with the dissection flap and surrounding aortic tissues. Intraoperative findings are presented for comparison and further discussion.

Effect of cilostazol on treadmill walking, community-based walking ability, and health-related quality of life in patients with intermittent claudication due to peripheral arterial disease: meta-analysis of six randomized controlled trials.

OBJECTIVES: To assess whether cilostazol, a phosphodiesterase III inhibitor, improves treadmill and community-based walking ability and health-related quality of life (HQL) in patients with intermittent claudication resulting from peripheral arterial disease (PAD). DESIGN: Retrospective meta-analysis of data pooled from six Phase 3, multicenter, double-blind, placebo-controlled, parallel-group, randomized studies. SETTING: Patients were recruited from outpatient ambulatory medical care facilities. PARTICIPANTS: Patients' (n = 1,751) mean age +/- standard deviation was 65 +/- 9, and they had a history of PAD for 6 months or longer and an ankle brachial index (ABI) of 0.90 or less. INTERVENTION: Cilostazol 50 mg bid or 100 mg bid for 12, 16, or 24 weeks. MEASUREMENTS: ABI; maximal walking distance (MWD); pain-free walking distance on a graded and constant-load treadmill; and HQL, measured using the Walking Impairment Questionnaire (WIQ) and the Medical Outcomes Study Short Form-36 (SF-36). RESULTS: Maximal treadmill walking distance improved more in both cilostazol groups than in the placebo group (both P <.0001). WIQ and SF-36 physical summary scores improved significantly more with cilostazol than with placebo (for instance, WIQ distance score, P <.0001 and SF-36 physical summary score, P <.0001, comparing persons taking cilostazol with controls). Improved MWD correlated with improvements in WIQ (correlation with distance score, r = 0.34, P <.0001) and SF-36 physical summary scores (r = 0.29, P <.0001). CONCLUSIONS: Treatment with cilostazol was associated with greater improvements in community-based walking ability and HQL in patients with intermittent claudication than treatment with placebo. These improvements correlated with increased MWD. This analysis of effects of cilostazol on improving walking ability in persons with claudication is the first cilostazol study focused on community-based measures of functional status and HQL. Questionnaires assessing walking ability and HQL provide important patient-based information about clinical outcomes of claudication therapy.

Vascular complications associated with pancreaticoduodenectomy adversely affect clinical outcome.

BACKGROUND: Early survival after pancreaticoduodenectomy has improved, but its morbidity remains high. The purpose of this study is to determine how the intra-operative (OR) occurrence of major vascular complications affects the outcome of pancreaticoduodenectomy. METHODS: The medical records of 180 consecutive patients having pancreaticoduodenectomy from 1991 to 2001 were reviewed. Vascular complications were defined as "an unanticipated injury or thrombosis of a major vessel necessitating intervention." Age, sex, type of pancreaticoduodenectomy, tumor size, estimated blood loss, OR time, time in intensive care, post-OR hospitalization, and survival were compared. RESULTS: Eighteen vascular complications were identified. Differences in age, sex, and type of resection between patients with or without vascular complications were not significant. OR time, estimated blood loss, blood transfusions, tumor size, time in intensive care, and post-OR hospitalization were all significantly greater in patients with vascular complications. Median survival for patients with vascular complications was significantly shorter than for patients without vascular complications. Thirty-day mortality was greater in patients with vascular complications. CONCLUSION: Vascular complications significantly affect the outcome of pancreaticoduodenectomy increasing OR time, estimated blood loss, blood transfusion requirements, time in intensive care, post-OR hospitalization, and mortality.

Vulnerable blood in high risk vascular patients: study design and methods.

BACKGROUND: Basic research suggests that rapid increases in circulating inflammatory and hemostatic blood markers may trigger or indicate impending plaque rupture and coronary thrombosis, resulting in acute ischemic heart disease (IHD) events. However, these associations are not established in humans. METHODS AND RESULTS: The Biomarker Risk Assessment in Vulnerable Outpatients (BRAVO) Study will determine whether levels of inflammatory and hemostatic biomarkers rapidly increase during the weeks prior to an acute IHD event in people with lower extremity peripheral artery disease (PAD). The BRAVO Study will determine whether biomarker levels measured immediately prior to an IHD event are higher than levels not preceding an IHD event; whether participants who experience an IHD event (cases) have higher biomarker levels immediately prior to the event and higher biomarker levels at each time point leading up to the IHD event than participants without an IHD event (controls); and whether case participants have greater increases in biomarkers during the months leading up to the event than controls. BRAVO enrolled 595 patients with PAD, a population at high risk for acute IHD events. After a baseline visit, participants returned every two months for blood collection, underwent an electrocardiogram to identify new silent myocardial infarctions, and were queried about new hospitalizations since their prior study visit. Mortality data were also collected. Participants were followed prospectively for up to three years. CONCLUSIONS: BRAVO results will provide important information about the pathophysiology of IHD events and may lead to improved therapies for preventing IHD events in high-risk patients.

Repair of a complex thoracic aneurysm from relapsing polychondritis.

A 29-year-old female with a history of relapsing polychondritis (RP) and open repair of a proximal descending thoracic aneurysm presented with 2 areas of asymptomatic thoracic aortic aneurysmal dilatation. The patient returned 3 months later with symptomatic aneurysm expansion, and she underwent ascending aortic arch replacement. She subsequently underwent staged endovascular repair of the distal descending thoracic aorta. RP is a rare disorder with an incidence of 3.5 per million persons annually, 4% to 7% of whom develop aneurysmal disease. Because of the aneurysmal potential of this disease, it is important for vascular surgeons to be aware of its presentation and treatment. To our knowledge, this is the first reported case describing endovascular technique to treat such a patient.

Arteriovenous loop grafts for free tissue transfer.

Arteriovenous (AV) loop grafts are a type of vascular conduit that can be used to support free tissue transfer. Wounds of various etiologies may require free tissue transfer, and the AV loop graft is a useful adjunct when adjacent blood supply is inadequate. Here we present 2 cases and review the technique and published literature.

Superficial femoral artery plaque, the ankle-brachial index, and leg symptoms in peripheral arterial disease: the walking and leg circulation study (WALCS) III.

BACKGROUND: The clinical significance of magnetic resonance-imaged plaque characteristics in the superficial femoral artery (SFA) is not well established. We studied associations of the ankle-brachial index (ABI) and leg symptoms with MRI-measured plaque area and percent lumen area in the SFA in participants with and without lower-extremity peripheral arterial disease (PAD). METHODS AND RESULTS: Four hundred twenty-seven participants (393 with PAD) underwent plaque imaging of the first 30 mm of the SFA. Twelve 2.5-mm cross-sectional images of the SFA were obtained. Outcomes were normalized plaque area, adjusted for artery size (0 to 1 scale, 1=greatest plaque), and lumen area, expressed as a percent of the total artery area. Adjusting for age, sex, race, smoking, statins, cholesterol, and other covariates, lower ABI values were associated with higher normalized mean plaque area (ABI <0.50:0.79; ABI 0.50 to 0.69:0.73; ABI 0.70 to 0.89:0.65; ABI 0.90 to 0.99:0.62; ABI 1.00 to 1.09:0.48; ABI 1.10 to 1.30:0.47 (P trend <0.001)) and smaller mean percent lumen area (P trend <0.001). Compared with PAD participants with intermittent claudication, asymptomatic PAD participants had lower normalized mean plaque area (0.72 versus 0.65, P=0.005) and larger mean percent lumen area (0.30 versus 0.36, P=0.01), adjusting for the ABI and other confounders. CONCLUSIONS: Lower ABI values are associated with greater MRI-measured plaque burden and smaller lumen area in the first 30 mm of the SFA. Compared with PAD participants with claudication, asymptomatic PAD participants have smaller plaque area and larger lumen area in the SFA. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00520312.