The impact of prolonged lower limb ischemia on amputation, mortality, and functional status: the FRIENDS registry.

BACKGROUND: Peripheral artery disease (PAD) is a major cause of cardiovascular ischemic events and amputation. Knowledge gaps exist in defining and measuring key factors that predict these events. The objective of this study was to assess whether duration of limb ischemia would serve as a major predictor of limb and patient survival. METHODS: The FReedom from Ischemic Events: New Dimensions for Survival (FRIENDS) registry enrolled consecutive patients with limb-threatening peripheral artery disease at a single tertiary care hospital. Demographic information, key clinical care time segments, functional status and use of revascularization, and pharmacotherapy data were collected at baseline, and vascular ischemic events, cardiovascular mortality, and all-cause mortality were recorded at 30 days and 1 year. RESULTS: A total of 200 patients with median (interquartile range) age of 76 years (65-84 years) were enrolled in the registry. Median duration of limb ischemia was 0.75 days for acute limb ischemia (ALI) and 61 days for chronic critical limb ischemia (CLI). Duration of limb ischemia of <12, 12 to 24, and >24 hours in patients with ALI was associated with much higher rates of first amputation (P = .0002) and worse amputation-free survival (P = .037). No such associations were observed in patients with CLI. CONCLUSIONS: For individuals with ischemic symptoms <14 days, prolonged limb ischemia is associated with higher 30-day and 1-year amputation, systemic ischemic event rates, and worse amputation-free survival. No such associations are evident for individuals with chronic CLI. These data imply that prompt diagnosis and revascularization might improve outcomes for patients with ALI.

The FReedom from Ischemic Events-New Dimensions for Survival (FRIENDS) registry: design of a prospective cohort study of patients with advanced peripheral artery disease.

BACKGROUND: Advanced lower extremity peripheral artery disease (PAD), whether presenting as acute limb ischemia (ALI) or chronic critical limb ischemia (CLI), is associated with high rates of cardiovascular ischemic events, amputation, and death. Past research has focused on strategies of revascularization, but few data are available that prospectively evaluate the impact of key process of care factors (spanning pre-admission, acute hospitalization, and post-discharge) that might contribute to improving short and long-term health outcomes. METHODS/DESIGN: The FRIENDS registry is designed to prospectively evaluate a range of patient and health system care delivery factors that might serve as future targets for efforts to improve limb and systemic outcomes for patients with ALI or CLI. This hypothesis-driven registry was designed to evaluate the contributions of: (i) pre-hospital limb ischemia symptom duration, (ii) use of leg revascularization strategies, and (iii) use of risk-reduction pharmacotherapies, as pre-specified factors that may affect amputation-free survival. Sequential patients would be included at an index "vascular specialist-defined" ALI or CLI episode, and patients excluded only for non-vascular etiologies of limb threat. Data including baseline demographics, functional status, co-morbidities, pre-hospital time segments, and use of medical therapies; hospital-based use of revascularization strategies, time segments, and pharmacotherapies; and rates of systemic ischemic events (e.g., myocardial infarction, stroke, hospitalization, and death) and limb ischemic events (e.g., hospitalization for revascularization or amputation) will be recorded during a minimum of one year follow-up. DISCUSSION: The FRIENDS registry is designed to evaluate the potential impact of key factors that may contribute to adverse outcomes for patients with ALI or CLI. Definition of new "health system-based" therapeutic targets could then become the focus of future interventional clinical trials for individuals with advanced PAD.

Chronic venous ulcer: minimally invasive treatment of superficial axial and perforator vein reflux speeds healing and reduces recurrence.

BACKGROUND: Chronic venous ulcer (CVU) is common and is responsible for significant health care expenditures worldwide. Compression is the mainstay of treatment, but long-term compliance with this therapy is often inconsistent, particularly in the elderly and infirm. Surgical ablation of axial and perforator reflux has been used as an adjunct to compression to reduce recurrence rates and assist healing. These surgical techniques are being replaced by minimally invasive procedures, such as thermal ablation and foam sclerotherapy, in the treatment of uncomplicated venous disease. The role for these techniques in the treatment of CVU is just beginning to be defined. METHODS: Eighty-six patients with CVU with 95 active ulcers (Clinical, Etiology, Anatomy, Physiology-CEAP clinical class 6) presenting to a multispecialty wound clinic were retrospectively reviewed and analyzed by leg. All patients underwent duplex scanning for venous insufficiency. Ulcer dimensions at each visit were recorded and used to calculate healing rates. Presence or absence of ulcer recurrence at 1-year follow-up was recorded. Ulcers treated with compression alone ("compression group") were compared with those treated with compression and minimally invasive interventions, such as thermal ablation of superficial axial reflux and ultrasound-guided foam sclerotherapy (UGFS) of incompetent perforating veins and varicosities ("intervention group"). RESULTS: The average age in the intervention and compression groups was 67 and 71 years, respectively (P = not significant [NS]). Body mass index was 32.4 ± 9.5 and 33.6 ± 11.8 kg/m(2), in the compression and intervention groups, respectively (P = not significant [NS]). Ulcers were recurrent in 42% of the intervention group and 26% of the compression group (P = NS). In the intervention group, 33% had radiofrequency ablation of axial reflux, 31% had UGFS of perforators, and 29% had both treatments. The only complication of intervention was a single case of cellulitis requiring hospitalization. Compared with the compression group, the ulcers in the intervention group healed faster (9.7% vs. 4.2% per week; P = 0.001) and showed fewer recurrences at 1-year follow-up (27.1% vs. 48.9 %; P < 0.015). Multivariate analysis showed use of intervention was the strongest determinant of healing with a coefficient of variation of 7.432, SE 2.406, P = 0.003. Analysis of just the intervention group before and after intervention using matched pairs showed acceleration of healing after intervention from ranging from a median of 1.2% (interquartile range [IQR], 14.3) to 9.7% (IQR, 11.3) per week (P ≤ 0.001). CONCLUSIONS: Minimally invasive ablation of superficial axial and perforator vein reflux in patients with active CVU is safe and leads to faster healing and decreased ulcer recurrence when combined with compression alone in the treatment of CVU.

Outcomes related to antiplatelet or anticoagulation use in patients undergoing carotid endarterectomy.

BACKGROUND: The number of cases involving patients undergoing vascular procedures who are prescribed clopidogrel or warfarin as treatment options continues to rise. Our aim was to examine outcomes related to antiplatelet or anticoagulation therapy in patients undergoing carotid endarterectomy (CEA). METHODS: A retrospective review of 260 consecutive patients undergoing CEA. Data including patient demographics, operative details, perioperative use of aspirin (ASA), clopidogrel, or warfarin, and early and/or late outcome(s) were collected. Endpoints included postoperative morbidity and/or mortality rate(s) and bleeding complications. RESULTS: The study included 152 men and 108 women (mean age = 69.3 years), with a mean follow-up of 406 days. In all, 46% of endarterectomies were for a symptomatic disease. The technique of eversion endarterectomy was applied in 126 (48.5%), Dacron-patch in 112 (43.1%), and bovine pericardial-patch in 14 (5.4%) of the cases. Among the patients, 171 were taking ASA, 50 were taking clopidogrel ± ASA, and 10 were taking warfarin (mean INR = 1.62; range, 1.2-2.1); the remaining 29 were not on any antiplatelet therapy. All patients who were on warfarin therapy underwent an eversion endarterectomy. Overall, there were 19 (7.3%) complications (12 major and seven minor). The 30-day stroke rate and stroke death rate was 0.7% and 1.1%, respectively. Patients taking clopidogrel developed more number of neck hematomas (16% vs. 1.7%, p = 0.0004) compared with patients who were on ASA alone. For patients taking clopidogrel, Dacron-patch repair resulted in more hematomas than eversion endarterectomy (35% vs. 4.2%, p = 0.012). There was no difference in the incidence of neck hematoma on the basis of endarterectomy technique in patients who were on ASA alone. The patients taking warfarin neither had a perioperative complication nor developed a neck hematoma. CONCLUSIONS: In this study, clopidogrel use during CEA resulted in a significant risk for developing a neck hematoma, particularly when using a Dacron-patch. The risk of a neck hematoma in patients who were on clopidogrel was much less when an eversion endarterectomy was performed.

The success and safety of endovenous ablation in patients with previous superficial venous thrombosis: a retrospective case-control study.

OBJECTIVES: Retrospective case-control study to determine the failure and endovenous heat-induced thrombosis (EHIT) rates of endovenous ablation (EVA) in patients with a history of superficial venous thrombosis (SVT). METHODS: Study and control groups each consisted of 73 patients with or without the history of SVT, who underwent EVA between June 2010 and July 2012. All patients were followed with venous duplex ultrasound. Procedural failure and EHIT rates were considered primary outcomes. RESULTS: There was no difference in EHIT or failure rates between study and control groups (P = 1.00). There was no difference in EHIT or failure rates between patients with and without the history of venous thromboembolism (VTE), with and without the history of VTE and/or SVT, with and without the history of thrombophilia, and on and off anticoagulation for either group or the combined study population. For the combined study population, failure rate was higher in patients with a history of VTE. CONCLUSIONS: Although EVA seems to be safe and effective in patients with a history of SVT, vein access in this patient group might require multiple attempts.

Supplemental oxygen reduces intimal hyperplasia after intraarterial stenting in the rabbit.

HYPOTHESIS: Supplemental oxygen can reduce intimal hyperplasia (IH) after stent deployment in a rabbit model. BACKGROUND: Endovascular stent placement is technically feasible, but long-term durability in vessels outside the aortoiliac system is compromised with postinterventional IH, which causes restenosis and failure of the arterial conduit. METHODS: Groups (n = 4 to 6) of female New Zealand white rabbits underwent placement of a 3-mm intraaortic stent with laparotomy and were placed in either normoxic (21% inspired oxygen concentration) or supplemental-oxygen (40% inspired oxygen concentration) environments for 0, 7, 14, and 28 days. The transarterial wall oxygen gradient was measured at 0, 7, and 28 days with an oxygen microelectrode. 5-Bromo-2'deoxyuridine (BrdU) was injected into the peritoneum before death to assess cellular proliferation. Aortic specimens were harvested en bloc and sectioned for analysis of cellular proliferation and intimal thickness. RESULTS: Intraaortic stent placement significantly decreased the transarterial wall oxygen gradient in the outer 70% of the vessel wall and was easily reversed at 7, 14, and 28 days with application of supplemental oxygen. Cellular proliferation was significantly decreased at 14 days (0.5% +/- 0.001% versus 2.3% +/- 0.002%; P <.001) and 28 days (0.4% +/- 0.001% versus 1.0% +/- 0.001%; P <.025) as measured with count of nuclei staining for 5-Bromo-2'deoxyuridine in the intima and media. Intimal thickness was significantly decreased at 28 days in oxygen-supplemented rabbits (intimal area/medial area = 0.50 +/- 0.07) as compared with controls (intimal area/medial area = 0.89 +/- 0.11; P <.025). CONCLUSION: This study shows the ability of supplemental oxygen to reverse arterial wall hypoxia, decrease cellular proliferation, and control IH at the deployment site of an intraarterial stent in a rabbit model. Forty-percent supplemental oxygen suppresses IH by 44% at 28 days as compared with normoxic control values. Cellular proliferation is reduced four-fold at 14 days and two-fold at 28 days in oxygen-supplemented rabbits as compared with control media after deployment. The clinical implications of these findings are significant, especially as the role of endovascular interventions continues to expand.

Expansion rates and outcomes for the 3.0-cm to the 3.9-cm infrarenal abdominal aortic aneurysm.

OBJECTIVE: This study was performed for the determination of the expansion rates and outcomes and for recommendations for the surveillance of the 3.0-cm to 3.9-cm abdominal aortic aneurysm (AAA). DESIGN: The study was observational with data from patients screened with ultrasound scanning for AAA at five Veterans Affairs Medical Centers for enrollment in the Aneurysm Detection and Management Trial. The eligibility requirements included: AAA from 3.0 cm to 3.9 cm in diameter and at least one repeat ultrasound scan more than 90 days after the initial screening. Patients also completed a questionnaire for demographic data and the determination of the presence of risk factors associated with AAA. The study endpoints included: 1, both mean and median expansion rates; 2, moderate expansion (>4 mm/year); 3, no expansion; 4, all causes of death; 5, AAA rupture; 6, expansion to 4 cm or more; 7, expansion to 5.0 cm or more; and 8, operative repair. RESULTS: Ultrasound scan screening results identified 1445 patients with 3.0-cm to 3.9-cm AAAs. Seven hundred ninety men met the ultrasound scan criterion of having at least two ultrasound scan studies during the study period, and these 790 men were used for this study. Mean AAA size was 3.3 cm, with an average follow-up period of 3.89 +/- 1.93 years. The median expansion rate was 0.11 cm/year. Expansion rates were significantly different (P <.001) between 3.0-cm and 3.4-cm cm AAA and 3.5-cm and 3.9-cm AAA. There were no reported AAA ruptures during the study period, although cause of death data were available in only 43% of the patients. Few 3.0-cm to 3.9-cm AAAs expanded to 5.0 cm or more during the study period. The patients with 3.0-cm to 3.9-cm AAAs who underwent operative repair during the study period were younger, had larger initial AAA diameters, and had more rapid expansion rates. CONCLUSION: AAAs of 3.0 cm to 3.9 cm expanded slowly, did not rupture, and rarely had operative repair or expanded to more than 5.0 cm in our study of male patients. Expansion rates and the incidence rate of operative repair are more common in the 3.5-cm to 3.9-cm AAA when compared with the 3.0-cm to 3.4-cm AAA.