Association of Survival With Femoropopliteal Artery Revascularization With Drug-Coated Devices.

Importance: In a recent meta-analysis of randomized clinical trials, femoropopliteal artery revascularization with paclitaxel drug-coated devices was associated with increased long-term all-cause mortality compared with non-drug-coated devices. However, to our knowledge, these findings have not been replicated in other data sources and may be subject to confounding from missing data associated with patient withdrawal and loss to follow-up. Objective: To evaluate differences in all-cause mortality between patients who were treated with drug-coated devices vs non-drug-coated devices for femoropopliteal artery revascularization. Design, Setting, and Participants: This nationwide, multicenter retrospective cohort study included 16 560 Centers for Medicare and Medicaid Services beneficiaries who were admitted for femoropopliteal artery revascularization from January 1, 2016, to December 31, 2016. All-cause mortality was analyzed through September 30, 2017. Exposures: Drug-coated devices (drug-eluting stent [DES] or drug-coated balloon [DCB]) compared with non-drug-coated devices (bare metal stent or uncoated percutaneous transluminal angioplasty balloon). Main Outcomes and Measures: The primary outcome was all-cause mortality analyzed through the end of follow-up. Results: Among 16 560 patients treated at 1883 hospitals, the mean (SD) age was 72.9 (11) years, 7734 (46.7%) were men, 12 232 (73.9%) were white, 8222 (49.7%) currently or had previously used tobacco, 9817 (59.3%) had diabetes, and 8450 (51.0%) had critical limb ischemia (CLI). Drug-coated devices were used in 5989 participants (36.2%). The median follow-up was 389 days (interquartile range, 277-508 days). Among all patients, treatment with drug-coated devices was associated with a lower cumulative incidence of all-cause mortality compared with treatment with non-drug-coated devices through 600 days postprocedure (32.5% vs 34.3%, respectively; log-rank P = .007). Similar survival trends were observed when treatment was stratified by using a DCB alone or DES with or without DCB. After multivariable adjustment, drug-coated devices were not associated with a difference in all-cause mortality compared with non-drug-coated devices (hazard ratio [HR], 0.97; 95% CI, 0.91-1.04; P = .43). These findings were consistent among those with CLI (HR, 0.93; 95% CI, 0.85-1.01; P = .09) or without CLI (HR, 0.94; 95% CI, 0.85-1.03; P = .20), and for those treated with DCB alone (HR, 0.94; 95% CI, 0.86-1.03; P = .17) or DES with or without DCB (HR, 0.97; 95% CI, 0.89-1.06; P = .48). Conclusions and Relevance: In this large nationwide analysis of Centers for Medicare and Medicaid Services beneficiaries, there was no evidence of increased all-cause mortality following femoropopliteal artery revascularization with drug-coated devices compared with non-drug-coated devices.

Clinical Outcomes and Cost Comparisons of Stent and Non-Stent Interventions in Infrainguinal Peripheral Artery Disease: Insights From the Excellence in Peripheral Artery Disease (XLPAD) Registry.

BACKGROUND: The contemporary limb outcomes and costs of stent-based vs non-stent based strategies in endovascular revascularization of femoropopliteal (FP) peripheral artery disease (PAD) are not well understood. METHODS AND RESULTS: We present data from the ongoing United States multicenter Excellence in Peripheral Artery Disease Registry between 2006-2016 to compare stent vs non-stent treatment outcomes and associated costs in FP interventions. A total of 2910 FP interventions were performed in 2162 patients (mean age, 66 years), comprising 1339 stent based (superficial femoral artery, 93%) in 1007 patients and 1571 non-stent interventions (superficial femoral artery, 85%) in 1155 patients. A growing trend for non-stent based interventions and a declining trend in repeat revascularization rate at 1 year were observed across years of registry enrollment. Stent implantation was the prevailing strategy in treating longer FP lesions (mean length, 152 mm vs 105 mm; P<.001) and chronic total occlusions (65% vs 40%; P<.001), while stent implantation was employed less frequently when treating in-stent restenotic lesions (14% vs 20%; P<.001). Stent and non-stent interventions had similar 1-year limb outcomes in all-cause death, target-limb revascularization, target-vessel revascularization, and major or minor amputation. The average procedure costs for the stent group were significantly higher than the non-stent group ($6215 vs $4790; P<.001). CONCLUSION: There is a growing trend for non-stent FP artery interventions, with a significant decline in 1-year target-limb revascularization rates over time. One-year limb outcomes in stent-based compared to non-stent interventions are similar; however, at a significantly higher procedural cost.

Assessment of longitudinal distribution of subclinical atherosclerosis in femoral arteries by three-dimensional cardiovascular magnetic resonance vessel wall imaging.

BACKGROUND: Lower extremity peripheral artery disease has become a significant health burden worldwide. Since the treatment strategies can be different if atherosclerotic disease involves different femoral artery segments, it is important to assess plaque distribution among different segments of femoral arteries. We sought to investigate the longitudinal distribution of subclinical femoral artery atherosclerosis in asymptomatic elderly adults using cardiovascular magnetic resonance (CMR) vessel wall imaging. METHODS: Asymptomatic elderly subjects underwent three-dimensional (3D) CMR vessel wall imaging for femoral arteries. The 3D motion sensitized-driven equilibrium prepared rapid gradient-echo (3D-MERGE) sequence was acquired from the common femoral artery to the popliteal artery. The femoral artery was divided into 4 segments: common femoral artery (CFA), proximal superficial femoral artery (pSFA), adductor canal (AC) segment of femoral artery, and popliteal artery (PA). The morphological characteristics including lumen area, wall area, maximum and minimum wall thickness, normalized wall index (NWI = wall area / [lumen area + wall area] × 100%), and eccentricity index ([maximum wall thickness - minimum wall thickness] / maximum wall thickness), luminal stenosis, and presence of atherosclerotic plaque were evaluated and compared between bilateral sides and among different femoral artery segments in each side of femoral artery. The associations between ankle-brachial index (ABI) and cardiovascular risk factors and femoral artery plaque characteristics were also determined. RESULTS: Of 107 recruited subjects (71.9 ± 5.6 years; 48 males), 70 (65.4%) were found to have femoral artery plaques. The atherosclerotic plaques were most frequently found in PA (41.1%) and CFA (40.2%) segments, followed by pSFA (31.8%) and AC (23.4%) segments (p = 0.002). Similarly, PA and CFA segments showed significantly greater maximum wall thickness and eccentricity index compared with pSFA and AC segments (all p < 0.001). Significant differences can be found in NWI among four segments of femoral arteries (p < 0.001) and PA showed the highest NWI (54.8%), followed by AC (54.3%), pSFA (52.4%) and CFA (45.9%) segments. Compared with right femoral artery, left femoral artery had significant smaller lumen area and greater NWI in most of segments (p < 0.002). There were no significant differences in ABI between subjects with and without atherosclerotic plaques (p = 0.161). The presence of subclinical atherosclerotic plaque in femoral arteries was significantly associated with cardiovascular risk factors including age (odds ratio [OR], 1.133; 95% confidence interval [CI], 1.048-1.224, p = 0.002), male gender (OR, 3.914; 95% CI, 1.612-9.501, p = 0.003), and hypertension (OR, 4.000; 95% CI, 1.700-9.411, p = 0.001), respectively. CONCLUSIONS: Subclinical femoral artery atherosclerosis is prevalent in the elderly population, particularly in the left femoral artery and segments of CFA and PA, and is associated with age, male gender and hypertension. Our findings suggest that, for screening subclinical atherosclerosis, more attention needs to be paid to the specific side and segments of femoral arteries, particularly older individuals and those with these cardiovascular disease risk factors.

Assessment of extracellular matrix-related biomarkers in patients with lower extremity artery disease.

BACKGROUND: The prevalence of lower extremity artery disease (LEAD) is high (20%-25%) in the population older than 65 years, but patients are seldom identified until the disease is advanced. Circulating markers of disease activity might provide patients with a key opportunity for timely treatment. We tested the hypothesis that measuring blood-specific fragments generated during degradation of the extracellular matrix (ECM) could provide further insight into the pathophysiologic mechanism of arterial remodeling. METHODS: The protein profile of diseased arteries from patients undergoing infrainguinal limb revascularization was assessed by a liquid chromatography and tandem mass spectrometry, nontargeted proteomic approach. The information retrieved was the basis for measurement of neoepitope fragments of ECM proteins in the blood of 195 consecutive patients with LEAD by specific enzyme-linked immunosorbent assays. RESULTS: Histologic and proteomic analyses confirmed the structural disorganization of affected arteries. Fourteen of 81 proteins were identified as differentially expressed in diseased arteries with respect to healthy tissues. Most of them were related to ECM components, and the difference in expression was used in multivariate analyses to establish that severe arterial lesions in LEAD patients have a specific proteome. Analysis of neoepitope fragments in blood revealed that fragments of versican and collagen type IV, alone or in combination, segregated patients with mild to moderate symptoms (intermittent claudication, Fontaine I-II) from those with severe LEAD (critical limb ischemia, Fontaine III-IV). CONCLUSIONS: We propose noninvasive candidate biomarkers with the ability to be clinically useful across the LEAD spectrum.

Two-Year Clinical Outcomes of the CONSEQUENT Trial: Can Femoropopliteal Lesions be Treated with Sustainable Clinical Results that are Economically Sound?

PURPOSE: The previously reported 6-month angiographic and 12-month clinical outcomes of the CONSEQUENT trial demonstrated the safety and efficacy of a novel paclitaxel-resveratrol-coated balloon for the treatment of lesions in the femoropopliteal segment. The purpose of this report is to present the 2-year results including a cost-benefit analysis for Germany. MATERIALS AND METHODS: Patients with symptomatic peripheral artery occlusive disease in femoropopliteal lesions were randomized either to drug-coated balloon (DCB, n = 78) or plain old balloon angioplasty (POBA, n = 75). As secondary endpoints, the 2-year clinical results consisting of target lesion revascularization (TLR), patency and increase in walking distance were recorded. Based on the Kaplan-Meier analyses for TLR and other adverse events, a cost-benefit analysis was conducted for the German DRG system. RESULTS: There were no additional TLRs in both groups between 14 and 24 months so that the corresponding rates remained significantly different between the treatment groups (DCB: 19.1 vs. POBA 40.6%, p = 0.007). At 2 years, the patency rate was significantly higher in the DCB group (72.3 vs. 48.4%, p = 0.006). The walking distance increase was also significantly higher after DCB angioplasty (172 ± 103 vs. 52 ± 136 m, p = 0.001). We estimated 2-year cost savings of € 1111.97 per patient treated with DCB instead of POBA. CONCLUSIONS: The use of paclitaxel-resveratrol matrix-coated peripheral balloons compared to POBA was associated with a significantly reduced TLR rate, superior patency and substantial cost savings at 2 years. ClinicalTrials.gov Identifier NCT01970579.

Preoperative assessment of computerized tomography angiography to predict success for crossing long Trans-Atlantic Inter-Society Consensus D lesions using the optical coherence tomography catheter.

Objectives Optical coherence tomography chronic total occlusion catheter, the Ocelot (Avinger Inc., Redwood City, CA), has been utilized to cross Trans-Atlantic Inter-Society Consensus D lesions. This study evaluated the preoperative computerized tomography angiography of chronic total occlusions in the superficial femoral artery to predict clinical success. Methods We reviewed all patients who underwent lower extremity procedures with the Ocelot catheter from June 2014 to August 2016. Patients who had a preoperative computerized tomography angiography were evaluated. Final outcomes, plaque morphology, lesion length, calcium surface area, lesion location, and patient characteristics were analyzed. Results A total of 107 patients underwent lower extremity interventions with the Ocelot catheter. Seventy patients had a preoperative computerized tomography angiography scan prior to lower extremity intervention and 77% (54) had Trans-Atlantic Inter-Society Consensus D lesions that were crossed. Mean age was 62.8 years and 68.6% were male. Mean chronic total occlusion length was 182.7 mm (170.8 mm crossed vs. 222.6 mm uncrossed, p = 0.03). Calcium distribution differed significantly ( p<.01): circumferential (14.8 vs. 12.5%); eccentric (85 vs. 62.5%); and complete calcium occlusion (0 vs. 25%) for lesions that were crossed and uncrossed, respectively. Significant differences ( p<.0001) were found when calcium occlusion was less than 50% (87 vs. 31%), 51-75% (9.3 vs. 31.2%), and 76-100% (3.7 vs. 37.5%). Total calcium length in crossed lesion was 51.6 mm, and 92.8 mm in uncrossed lesions ( p = 0.10). No significant differences were noted for patient gender, occlusion location (proximal, middle, and distal superficial femoral artery), and kidney function. Conclusion The Ocelot catheter is an effective method to cross long Trans-Atlantic Inter-Society Consensus D lesions. Superficial femoral artery lesions longer than 17 cm and focal plaque morphology, specifically a total cross-sectional area of calcium and a calcium surface area greater than 50% were most predictive of failure to cross Trans-Atlantic Inter-Society Consensus D superficial femoral artery lesions. Computerized tomography angiography is an effective tool to predict success for crossing chronic total occlusions using optical coherence tomography technology and a critical consideration for patient selection.

Potential mechanisms of in-stent occlusion in the femoropopliteal artery: an angioscopic assessment.

Although stent implantation has become widespread for the treatment of patients with peripheral artery disease with femoropopliteal (FP) lesions, in-stent restenosis, especially in-stent occlusion (ISO), remains as a major concern for refractory recurrence. Furthermore, the mechanisms of ISO in FP lesions have not been well elucidated. We performed angioscopy for 6 lesions (bare-metal stent: 3, drug-eluting stent: 3) from 5 patients (mean age 74 ± 10 years, male 40 %) with ISO in the FP artery immediately after wire-passing or thrombus aspiration. The presence of thrombus as well as the presence and location of organic stenosis were evaluated. Median duration from stent implantation to angioscopic evaluation was 1099.5 (514.5-2272.5) days, while the duration from recurrence of symptoms to angioscopic evaluation was 45 (5.75-60) days. Mixed thrombi were observed in all stents. Organic stenosis was detected at the proximal edge of the stents in 5 lesions. Organic stenosis was observed at the overlapping segment of the stent in one lesion. The distal edge of the stents could be evaluated in 3 lesions, and all of them showed organic stenosis at the site. Mixed thrombi and organic stenosis were observed in all stents. Partial development of organic stenosis in a stent followed by thrombus formation may be the potential mechanism of the development of ISO in the FP artery though the sample size of this study was small and it had no serial angioscopic data so that we should consider it as preliminary one at best.

Lesion complexity drives the cost of superficial femoral artery endovascular interventions.

OBJECTIVE: Patients who undergo endovascular treatment of superficial femoral artery (SFA) disease vary greatly in lesion complexity and treatment options. This study examined the association of lesion severity and cost of SFA stenting and to determine if procedure cost affects primary patency at 1 year. METHODS: A retrospective record review identified patients undergoing initial SFA stenting between January 1, 2010, and February 1, 2012. Medical records were reviewed to collect data on demographics, comorbidities, indication for the procedure, TransAtlantic Inter-Society Consensus (TASC) II severity, and primary patency. The interventional radiology database and hospital accounting database were queried to determine cost drivers of SFA stenting. Procedure supply cost included any item with a bar code used for the procedure. Associations between cost drivers and lesion characteristics were explored. Primary patency was determined using Kaplan-Meier survival curves and a log-rank test. RESULTS: During the study period, 95 patients underwent stenting in 98 extremities; of these, 61% of SFA stents were performed for claudication, with 80% of lesions classified as TASC II A or B. Primary patency at 1 year was 79% for the entire cohort. The mean total cost per case was $10,333. Increased procedure supply cost was associated with adjunct device use, the number of stents, and TASC II severity. Despite higher costs of treating more complex lesions, primary patency at 1 year was similar at 80% for high-cost (supply cost >$4000) vs 78% for low-cost (supply cost <$4000) interventions. CONCLUSIONS: SFA lesion complexity, as defined by TASC II severity, drives the cost of endovascular interventions but does not appear to disadvantage patency at 1 year. Reimbursement agencies should consider incorporating disease severity into reimbursement algorithms for lower extremity endovascular interventions.

Fast segmentation of the femoral arteries from 3D MR images: A tool for rapid assessment of peripheral arterial disease.

PURPOSE: The peripheral arterial disease is a powerful indicator of coexistent generalized atherosclerosis. As plaques in femoral arteries are diffused and can span a length of 30 cm, a large coverage of the arteries is required to assess the full extent of atherosclerosis. Recent development of 3D black-blood magnetic resonance imaging sequences has allowed fast acquisition of images with an extended longitudinal coverage. Vessel wall volume quantification requires the segmentation of the lumen and outer wall boundaries, and conventional manual planimetry would be too time-consuming to be feasible for analyzing images with such a large coverage. To address this challenge in image analysis, this work introduces an efficient 3D algorithm to segment the lumen and outer wall boundaries for plaque and vessel wall quantification in the femoral artery. METHODS: To generate the initial lumen surface, a user identified the location of the lumen centers manually on a set of transverse images with a user-specified interslice distance (ISD). A number of geometric operators were introduced to automatically adjust the initial lumen surface based on pixel intensity and gradient along the boundary and at the center of each transverse slice. The adjusted surface was optimized by a 3D deformable model driven by the local stiffness force and external force based on image gradient. The optimized lumen surface was expanded to obtain the initial outer wall surface, which was subsequently optimized by the 3D deformable model. RESULTS: The algorithm was executed with and without adjustment of the initial lumen surface and for three different selections of ISD: 10, 20, and 30 mm. The segmentation accuracy was improved in a statistically significant way with the introduction of initial lumen surface adjustment, but was insensitive to the ISD setting. When compared with the manual segmentation, the settings with adjustment have, on average, mean absolute differences (MADs) of 0.28 and 0.36 mm, respectively, for lumen and outer wall segmentations, which are significantly lower than those obtained when the adjustment operators were not applied (MAD = 0.43 and 0.59 mm for lumen and outer wall segmentations). The algorithm took about 1% of the time required for manual segmentation to complete segmenting the whole 3D femoral artery. CONCLUSIONS: The proposed semiautomatic algorithm generated accurate lumen and outer wall boundaries from 3D black-blood MR images with few user interactions, thereby allowing rapid and streamlined assessment of plaque burden in the femoral arteries.

The Association Between the Cardio-ankle Vascular Index and Other Parameters of Vascular Structure and Function in Caucasian Adults: MARK Study.

AIM: We assessed whether there is an association between the cardio-ankle vascular index (CAVI) score and the carotid intima media thickness (IMT), the pulse wave velocity (PWV) and the central augmentation index (CAIx) that is independent of the subject's cardiovascular risk and pharmacological treatment. METHODS: The CAVI score was measured in 500 subjects using a VaSera device and the brachial ankle PWV (ba-PWV) was calculated. A carotid ultrasound was used to measure the IMT. A Mobil-O-Graph device was used to measure the carotid femoral PWV (cf-PWV) and the CAIx. The Framingham-D'Agostino and SCORE scales were used to measure the subject's cardiovascular risk. RESULTS: The mean value of the CAVI score was 8.59 ± 1.1. IMT, CAIx and PWV maintained a positive association with the CAVI score (p ＜ 0.01) in a multiple linear regression analysis, after adjusting for the subject's cardiovascular risk, body mass index and pharmacological treatment. The cut-off level that gave the maxima sensitivity and specificity to detect a mean IMT of ＞ 0.90 mm was 8.95 (AUC=0.67) for the CAVI score, 8.85 (AUC=0.66) for cf-PWV and 15.10 (AUC=0.66) for ba-PWV. The cut-off to detect a maxima IMT of ＞ 0.90 mm was 8.60 (AUC=0.62) for the CAVI score, 8.85 (AUC=0.64) for cf-PWV and 15.75 (AUC=0.70) for ba-PWV. CONCLUSION: There was a positive association of the CAVI score with vascular structure and function parameters that was independent of cardiovascular risk and any medications being used by the subject. The ability of the CAVI score to predict carotid atherosclerosis is similar to that of cf-PWV and ba-PWV in Caucasian adults.

Paclitaxel-eluting stents for the treatment of femoropopliteal arterial stenoses: focus on the Zilver PTX drug-eluting peripheral stent.

Restenosis is one of the major limitations of the percutaneous treatment of peripheral artery disease, leading to the need for repeat interventions, limb loss and increased cost of therapy. The current standard of percutaneous treatment of stenotic lesions in the femoropopliteal arterial segment includes balloon angioplasty and bare-metal stenting. Recently, research in the field adapting the coronary arterial bed treatment model led to the inclusion of antimitotic drugs in the form of drug-eluting stents to combat neointimal proliferation and reduce the burden of restenosis. Randomized trial and registry data emerged indicating improved long-term outcomes with drug-eluting stents in peripheral arteries, lending the way to more widespread adaptation of this modality in the management of patients with peripheral artery disease.

Comparison of the Complior Analyse device with Sphygmocor and Complior SP for pulse wave velocity and central pressure assessment.

BACKGROUND: The Complior device (Alam Medical, France) was used in epidemiological studies which established pulse wave velocity (PWV) as a cardiovascular risk marker. Central pressure is related, but complementary to PWV and also associated to cardiovascular outcomes. The new Complior Analyse measures both PWV and central blood pressure during the same acquisition. The aim of this study was to compare PWV values from Complior Analyse with the previous Complior SP (PWVcs) and with Sphygmocor (PWVscr; AtCor, Australia), and to compare central systolic pressure from Complior Analyse and Sphygmocor. METHOD: Peripheral and central pressures and PWV were measured with the three devices in 112 patients. PWV measurements from Complior Analyse were analysed using two foot-detection algorithms (PWVca_it and PWVca_cs). Both radial (ao-SBPscr) and carotid (car-SBPscr) approaches from Sphygmocor were compared to carotid Complior Analyse measurements (car-SBPca). The same distance and same calibrating pressures were used for all devices. RESULTS: PWVca_it was strongly correlated to PWVscr (R(2) = 0.93, P < 0.001) with a difference of 0.0 ±â€Š0.7  m/s. PWVca_cs was also correlated to PWVcs (R(2) = 0.90, P < 0.001) with a difference of 0.1 ±â€Š0.7  m/s. Central systolic pressures were strongly correlated. The difference between car-SBPca and ao-SBPscr was 3.1 ±â€Š4.2  mmHg (P < 0.001), statistically equivalent to the difference between car-SBPscr and ao-SBPscr (3.9 ±â€Š5.8  mmHg, P < 0.001), whilst the difference between car-SBPca and car-SBPscr was negligible (-0.7 ±â€Š5.6  mmHg, P = NS). CONCLUSION: The new Complior Analyse device provides equivalent results for PWV and central pressure values to the Sphygmocor and Complior SP. It reaches Association for the Advancement of Medical Instrumentation standard for central blood pressure and grades as excellent for PWV on the Artery Society criteria. It can be interchanged with existing devices.

Assessment of femoral artery atherosclerosis at the adductor canal using 3D black-blood MRI.

AIM: To assess whether the three-dimensional (3D) black-blood motion-sensitized driven equilibrium (MSDE) prepared rapid gradient-echo sequence (3D MERGE) magnetic resonance imaging (MRI) sequence is sensitive enough to detect differences in atherosclerotic plaque size and morphology occurring in the adductor canal and the proximal bifurcation segment. MATERIALS AND METHODS: Fifty pairs of adductor canal and bifurcation segments from 25 patients with intermittent claudication were examined using 3D MERGE. The two-dimensional (2D) transverse section showing the largest plaque burden in each segment was chosen for comparison. Wall and lumen boundaries were segmented from each 2D section and quantified using six metrics: wall area (WA), lumen area (LA), normalized wall index (NWI), maximum wall thickness (MaxWT), minimum wall thickness (MinWT), and eccentricity. RESULTS: The mean LA in the adductor region was significantly lower than that in the bifurcation segment (p < 0.0001). Mean NWI, MaxWT, and eccentricity in the adductor region were significantly higher than those at bifurcation (p < 0.0001, p < 0.0021, and p < 0.0045, respectively). Mean WA and MinWT of the two segments did not show a statistically significant difference. WA in both regions was positively correlated with eccentricity (p < 0.0049 and p < 0.0049, respectively). LA was negatively correlated with eccentricity (p < 0.0017), and NWI was positively correlated with eccentricity only in the adductor region (p < 0.0004). CONCLUSION: The results suggest that compensatory enlargement was limited in the adductor canal when compared to the proximal bifurcation segment. 3D MERGE, as a fast and non-invasive sequence, may assist the evaluation of femoral atherosclerosis by assessing the size and morphology of plaques, knowledge of which can guide clinical treatment.

Assessment of gene expression profiles in peripheral occlusive arterial disease.

BACKGROUND: Molecular events responsible for the onset and progression of peripheral occlusive arterial disease (POAD) are incompletely understood. Gene expression profiling may point out relevant features of the disease. METHODS: Tissue samples were collected as operatory waste from a total of 36 patients with (n = 18) and without (n = 18) POAD. The tissues were histologically evaluated, and the patients with POAD were classified according to Leriche-Fontaine (LF) classification: 11% with stage IIB, 22% with stage III, and 67% with stage IV. Total RNA was isolated from all samples and hybridized onto Agilent 4×44K Oligo microarray slides. The bioinformatic analysis identified genes differentially expressed between control and pathologic tissues. Ten genes with a fold change ≥ 2 (1 with a fold change ≥ 1.8) were selected for quantitative polymerase chain reaction validation (GPC3, CFD, GDF10, ITLN1, TSPAN8, MMP28, NNMT, SERPINA5, LUM, and FDXR). C-reactive protein (CRP) was assessed with a specific assay, while nicotinamide N-methyltransferase (NNMT) was evaluated in the patient serum by enzyme-linked immunosorbent assay. RESULTS: A multiple regression analysis showed that the level of CRP in the serum is correlated with the POAD LF stages (r(2) = 0.22, P = 0.046) and that serum NNMT is higher in IV LF POAD patients (P = 0.005). The mRNA gene expression of LUM is correlated with the LF stage (r(2) = 0.45, P = 0.009), and the mRNA level of ITLN1 is correlated with the ankle-brachial index (r(2) = 0.42, P = 0.008). CONCLUSIONS: Our analysis shows that NNMT, ITLN1, LUM, CFD, and TSPAN8 in combination with other known markers, such as CRP, could be evaluated as a panel of biomarkers of POAD.

Arterial ultrasound screening as a tool for coronary risk assessment in asymptomatic men and women.

One of the imaging tests most commonly used to assess cardiovascular diseases (CVDs) in daily practice is Doppler ultrasonography of the carotid and femoral arteries. We included 2709 participants with no history or symptoms of CVD; they had a risk factor assessment and a carotid and femoral ultrasonography at baseline. Incident cases of definite coronary events were recorded during a median follow-up of 6 years. Approximately, 63% of the sample presented abnormalities (carotid stenosis >50%, carotid plaque, femoral plaque, increased intima-media thickness [IMT]). A moderately increased IMT (>0.63 mm) or the presence of carotid or femoral artery plaque was related to prognosis. The associations persisted after adjustment for pretest risk, treatment with statins, and other Doppler ultrasonography abnormalities. The hazard ratio increased significantly with the number of abnormalities (varying from 2.35 [1.16-4.74] to 14.83 [6.47-33.9]).

Fast plaque burden assessment of the femoral artery using 3D black-blood MRI and automated segmentation.

PURPOSE: Vessel wall imaging techniques have been introduced to assess the burden of peripheral arterial disease (PAD) in terms of vessel wall thickness, area or volume. Recent advances in a 3D black-blood MRI sequence known as the 3D motion-sensitized driven equilibrium (MSDE) prepared rapid gradient echo sequence (3D MERGE) have allowed the acquisition of vessel wall images with up to 50 cm coverage, facilitating noninvasive and detailed assessment of PAD. This work introduces an algorithm that combines 2D slice-based segmentation and 3D user editing to allow for efficient plaque burden analysis of the femoral artery images acquired using 3D MERGE. METHODS: The 2D slice-based segmentation approach is based on propagating segmentation results of contiguous 2D slices. The 3D image volume was then reformatted using the curved planar reformation (CPR) technique. User editing of the segmented contours was performed on the CPR views taken at different angles. The method was evaluated on six femoral artery images. Vessel wall thickness and area obtained before and after editing on the CPR views were assessed by comparison with manual segmentation. Difference between semiautomatically and manually segmented contours were compared with the difference of the corresponding measurements between two repeated manual segmentations. RESULTS: The root-mean-square (RMS) errors of the mean wall thickness (t(mean)) and the wall area (WA) of the edited contours were 0.35 mm and 7.1 mm(2), respectively, which are close to the RMS difference between two repeated manual segmentations (RMSE: 0.33 mm in t(mean), 6.6 mm(2) in WA). The time required for the entire semiautomated segmentation process was only 1%-2% of the time required for manual segmentation. CONCLUSIONS: The difference between the boundaries generated by the proposed algorithm and the manually segmented boundary is close to the difference between repeated manual segmentations. The proposed method provides accurate plaque burden measurements, while considerably reducing the analysis time compared to manual review.

Peripheral plaque volume changes pre- and post-rotational atherectomy followed by directional plaque excision: assessment by intravascular ultrasound and virtual histology.

Atherectomy in the infra-inguinal peripheral vascular bed may be an effective alternative to the balloon and stent-based approach. The change in plaque volume and composition with rotational atherectomy and directional plaque excision has not been studied. We performed rotational atherectomy (RA) followed by adjunctive plaque excision (PE) in 8 patients with infra-inguinal lesions. Lesions were assessed by quantitative angiography and intravascular ultrasound (IVUS) with virtual histology (VH) pretreatment, post-RA, and post-PE. Paired t-tests were used to assess the change in plaque volume, luminal area and dimensions and overall vessel size. Total plaque volume decreased by 24% (347 +/- 118 to 264 +/- 85 mm(3); p = 0.03), which resulted in a lumen increase of 66% (7.08 +/- 3 to 11.7 +/- 2.8 mm(2); p = 0.006). This was mainly due to PE compared to RA. This was achieved without any significant increase in the overall vessel area (27.4 +/- 6.3 to 28 +/- 6.7 mm(2); p = 0.42). The effect on minimal and maximal luminal diameters was synergistic between RA and PE. Fibrotic and fibrofatty plaque were amenable to PE, whereas necrotic core and dense calcium were less responsive to either atherectomy technique. In conclusion, RA followed by PE result in significant improvements in plaque volume and luminal area and diameter primarily by removing plaque rather than vessel expansion. This is mainly attributable to the removal of fibrotic and fibrofatty plaque.

[Femoral ultrasound in the assessment of preclinical atherosclerosis. Distribution of intima-media thickness and frequency of atheroma plaques in a Spanish community cohort]. / Ecografía femoral en la evaluación de la aterosclerosis preclínica. Distribución de valores del grosor íntima-media y frecuencia de placas de ateroma en una cohorte comunitaria española.

BACKGROUND AND OBJECTIVE: High-resolution B-mode ultrasound measurements of intima-media thickness (IMT) and plaque presence are useful to assess preclinical atherosclerosis. Normal carotid IMT values, but not normal femoral IMT values, have been reported in Spanish subjects. Our aim was to define the normality data of femoral ultrasound by sex and age. SUBJECTS AND METHOD: We studied 192 healthy subjects from a community cohort, 85 men and 107 women (mean age: 49 years; range: 20-81 years). We sonographically determined mean and maximum IMT in the far wall of the common femoral artery, plaque occurrence, and maximum plaque height. RESULTS: Reference values for femoral IMT, expressed as 25th, 50th, and 75th percentiles by sex and 5 age groups, were obtained. The 50th percentiles of mean IMT ranged from 0.50 to 1.04 mm in men in the age groups < or = 35 years and > or = 65 years, respectively. For women, corresponding IMT values ranged from 0.40 to 0.53 mm. IMT was positively related to age in both men (r = 0.44; p < 0.001) and women (r = 0.23; p = 0.019). From the regression equations of IMT versus age, the estimated yearly increase in IMT was 0.016 mm in men and 0.008 mm in women. More than 50% of men aged > or = 55 years and women aged > or = 65 years had plaques. CONCLUSIONS: Both IMT and plaque frequency are associated with age in men and women. Femoral IMT values in a Spanish community cohort are lower than those reported for geographical areas with higher cardiovascular risk, such as the Northern European countries and the US.

Clinical and pathological assessment of different suture techniques for microvascular anastomosis in rat femoral artery.

This study examined the clinical and pathological features after a microvascular anastomosis of a rat femoral artery using four different suture techniques. Sixty Sprage-Dawely rats were divided randomly into 4 groups. Fifteen bisected arteries (one from each animal) in Group I, II, III and IV were sutured with the simple interrupted suture, continuous suture, sleeve suture and cuff suture, respectively. The anastomosis times in Group I, II, III and IV were 28.67, 14.67, 15.47 and 15.93 min, respectively. Immediate bleeding that stopped without intervention (grade I) was observed in 67%, 73% and 60% of the anastomosed vessels in Groups II, III and IV, respectively, while 60% of the vessels in Group I showed light bleeding that was inhibited by gentile pressure (grade II). All vessels examined appeared to be patent at 5 and 15 min after the anastomosis. On the 7th day postoperatively, the vessels of Group I showed the highest patency rate (93%) compared with Groups II (67%), III (73%) and IV (87%). Moreover, there were more pronounced pathological changes in Group I than in the other groups. These changes included endothelial loss, endothelial proliferation, degeneration and necrosis of the tunica media. Suture materials surrounded by an inflammatory reaction were also observed. In conclusion, the simple interrupted suture is preferable for microvascular anastomosis due to its highest patency rate. The other techniques investigated can be good alternatives because of their short anastomotic time and moderate pathological changes.

A cost-minimization analysis of the angio-seal vascular closure device following percutaneous coronary intervention.

The Angio-Seal vascular closure device has been shown to be safe and effective in decreasing the time to hemostasis after percutaneous coronary intervention (PCI). The health economic implications of routinely using Angio-Seal after PCI have not been explored. We performed a cost-minimization analysis comparing routine Angio-Seal use after PCI with mechanical compression using a decision analytic model. The relative probabilities of 7 vascular access complications were derived from pooled analysis of published randomized trials. The incremental hospital cost of each vascular complication was estimated by a matched case-control analysis of 3,943 patients who underwent PCI at our center from January 2002 and December 2004. Appropriate sensitivity and uncertainty analyses were performed. After accounting for differences in expected rates of specific complications between the 2 strategies and the incremental costs of each vascular event, the routine use of Angio-Seal was associated with a lower cost per PCI procedure of 44 dollars. Probabilistic sensitivity analysis of all model assumptions using second-order Monte Carlo simulation confirmed the economic advantage of Angio-Seal in 74% of model replications. In conclusion, after PCI, the routine use of Angio-Seal for femoral vascular access management was associated with net cost savings compared with mechanical compression. This cost savings was in addition to the previously demonstrated advantages of Angio-Seal in terms of patient comfort and preference.