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Background: Patients with peripheral artery disease (PAD) are at increased risk for major adverse limb and cardiac events including mortality. Developing screening tools capable of accurate PAD identification is a necessary first step for strategies of adverse outcome prevention. This study aimed to determine whether machine analysis of a resting Doppler waveform using deep neural networks can accurately identify patients with PAD. Methods: Consecutive patients (4/8/2015 – 12/31/2020) undergoing rest and postexercise ankle–brachial index (ABI) testing were included. Patients were randomly allocated to training, validation, and testing subsets (70%/15%/15%). Deep neural networks were trained on resting posterior tibial arterial Doppler waveforms to predict normal (> 0.9) or PAD (⩽ 0.9) using rest and postexercise ABI. A separate dataset of 151 patients who underwent testing during a period after the model had been created and validated (1/1/2021 – 3/31/2021) was used for secondary validation. Area under the receiver operating characteristic curves (AUC) were constructed to evaluate test performance. Results: Among 11,748 total patients, 3432 patients met study criteria: 1941 with PAD (mean age 69 ± 12 years) and 1491 without PAD (64 ± 14 years). The predictive model with highest performance identified PAD with an AUC 0.94 (CI = 0.92–0.96), sensitivity 0.83, specificity 0.88, accuracy 0.85, and positive predictive value (PPV) 0.90. Results were similar for the validation dataset: AUC 0.94 (CI = 0.91–0.98), sensitivity 0.91, specificity 0.85, accuracy 0.89, and PPV 0.89 (postexercise ABI comparison). Conclusion: An artificial intelligence-enabled analysis of a resting Doppler arterial waveform permits identification of PAD at a clinically relevant performance level.

Clinical differentiation of buttock claudication from pseudo-claudication (neuromuscular etiology) is often challenging and cannot be diagnosed non-invasively using standard ankle-brachial index (ABI) with exercise. The aim of this study was to evaluate the reliability of exercise transcutaneous oximetry (ExTcPO2) to accurately detect significant internal iliac artery (IIA) inflow stenosis. Methods: Data from a prospectively maintained registry of consecutive patients undergoing ExTcPO2 for evaluation of buttock and hip exertional discomfort as well as arterial imaging within 12 months were retrospectively analyzed. ExTcPO2 was performed on a treadmill (10% slope; 2 mph speed); measured at buttocks, upper back and calf (rest, with exercise) to document the baseline normal, degree of change with exercise and recovery patterns. A Delta from Resting Oxygen Pressure (DROP) (buttock- back TcPO2 mmHg) ≥15 mm Hg was considered significant. A blinded physician performed aorto-iliac arterial stenosis quantification and receiver operating characteristic (ROC) curve analysis was used to determine sensitivity and specificity to diagnose severe inflow reduction (≥70%) based upon a diagnostic DROP ≥15 mm Hg. Results: One hundred and eleven patients (M:F::79:32, mean age 70, range 18-90 years) with available concomitant imaging (CTA 90, DUS 21) were included in the study. Indications for testing were suspected vascular (82), or neuromuscular (29) symptoms. ExTcPO2 study confirmed the clinical suspicion of the state of IAA inflow in 81% (91/111) of patients. DROP ≥15 mm Hg had a sensitivity, specificity, PPV, NPV of 56, 80, 70, and 68% respectively for prediction of severe IIA inflow reduction (p value

Objective To evaluate the relationship between peripheral arterial disease (PAD) and incident atrial fibrillation (AF) and its clinical and pathophysiologic implications on ischemic stroke and all-cause mortality. Patients and Methods We identified all adult patients in the Mayo Clinic Health System without a previous diagnosis of AF undergoing ankle-brachial index (ABI) testing for any indication from January 1, 1996, to June 30, 2018. Retrospective extraction of ABI data and baseline echocardiographic data was performed. The primary outcome of interest was incident AF. The secondary outcomes of interest were incident ischemic stroke and all-cause mortality. Results A total of 33,734 patients were included in the study. After adjusting for demographic and comorbidity variables, compared with patients who had normal ABI (1.0 to 1.39), there was an increased risk of incident AF in patients with low ABI ( Conclusion In this large cohort of ambulatory patients undergoing ABI measurement, patients with PAD were at increased risk for incident AF, ischemic stroke, and mortality. In these high-risk patients with abnormal ABI, particularly severe PAD and cardiac structural abnormalities, routine monitoring for AF and management of cardiovascular risk factors may be warranted.

The calf muscle pump is a major determinate of venous return in the legs but has not been studied as a risk factor for venous thromboembolism (VTE). A population-based cohort study of Olmsted County, Minnesota residents was performed using calf pump function (CPF) measurements from venous plethysmography studies from 1998 to 2015. Patients with a history of VTE were excluded. Nursing validated VTE outcomes from the Rochester Epidemiology Project were identified after the index study date, and patients with reduced CPF (rCPF) were compared with patients with normal CPF. A total of 1532 patients with recorded CPF (28% air and 72% strain gauge plethysmography) were included; 591 (38.5%) had normal CPF, 353 (23.0%) had unilateral rCPF, and 588 (38.3%) had bilateral rCPF. Any VTE occurred in 87 patients (5.7%) after a median follow-up of 11.7 years (range, 0-22.0 years). Comparing patients with bilateral reduced to bilateral normal CPF, the unadjusted hazard ratio (HR) for incident VTE was 2.0 (95% confidence interval [CI], 1.2-3.4) and after adjusting for age, BMI, and Charlson Comorbidity Index, the HR was 1.68 (95% CI, 0.98-2.89). The adjusted HR for ipsilateral deep vein thrombosis was evaluated in 3064 legs comparing legs with reduced to normal CPF and was 1.71 (95% CI, 1.03-2.84). Mortality was significantly higher in both the bilateral (P < .001) and unilateral (P < .001) rCPF groups compared with normal CPF. Our results demonstrate that CPF is a risk factor for VTE in an otherwise low-risk ambulatory population and might be a useful component in risk stratification models.

International audience; This expert consensus statement on the interpretation of peripheral arterial and venous spectral Doppler waveforms was jointly commissioned by the Society for Vascular Medicine (SVM) and the Society for Vascular Ultrasound (SVU). The consensus statement proposes a standardized nomenclature for arterial and venous spectral Doppler waveforms using a framework of key major descriptors and additional modifier terms. These key major descriptors and additional modifier terms are presented alongside representative Doppler waveforms, and nomenclature tables provide context by listing previous alternate terms to be replaced by the new major descriptors and modifiers. Finally, the document reviews Doppler waveform alterations with physiologic changes and disease states, provides optimization techniques for waveform acquisition and display, and provides practical guidance for incorporating the proposed nomenclature into the final interpretation report.

Introduction: Patients with concomitant peripheral artery disease (PAD) and heart failure (HF) are known to have increased morbidity and mortality. Though they share common risk factors, the utility of HF screening in patients with PAD remains controversial and without international consensus. We sought to clarify whether PAD is an independent risk factor for HF. Methods: We performed a retrospective analysis of adult patients without a history of heart failure who underwent ankle brachial index (ABI) measurement for any indication between 1995-2020. Patients were then stratified by ABI: PAD with low ABI (1.39). The associations between PAD and incident diagnosis of heart failure, systolic dysfunction (HF with reduced ejection fraction, HFrEF), and diastolic dysfunction (HF with preserved ejection fraction, HFpEF) were assessed. All patient and outcomes variables were obtained using the institutional electronic health record. Multivariable Cox proportional regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI) after adjusting for age, sex, hypertension, diabetes, and active tobacco use. Results: The cohort included 36,816 patients (median follow-up 4.21 years), of whom 2,116 (5.7%) were diagnosed with HF. Among HF patients, 1,110 (3.0%) had HFrEF and 1,006 (2.7%) had HFpEF. Both low and elevated ABI groups were associated with an increased risk of HF, both HFrEF, and HFpEF. After multivariable analysis, PAD with elevated ABI was associated with higher overall HF risk (HR, 2.36 [95% CI, 2.03, 2.73]) than low ABI (HR, 1.56 [95% CI, 1.40, 1.74]) when compared to normal ABI. Similarly, PAD with elevated ABI was associated with greater risk of HFrEF (HR, 2.37 [95% CI, 1.93, 2.92]) and HFpEF (HR, 1.82 [95% CI, 1.48, 2.25]) than PAD with low ABI (HFrEF: HR 1.77 [95% CI, 1.52, 2.07], HFpEF: HR 1.31 [95% CI, 1.12, 1.52]). Conclusions: PAD, especially with elevated ABI, is an independent risk factor for heart failure even after adjusting for common HF risk factors. Our findings support HF screening in PAD patients, but longitudinal data on HF morbidity and mortality is necessary to evaluate the value of this practice.

Introduction: Peripheral arterial disease (PAD) increases cardiovascular (CV) morbidity and mortality, but remains underdiagnosed and undertreated. Several trials support low-dose rivaroxaban in PAD treatment, although this has yet to be widely adopted in clinical practice. The effect of warfarin and direct oral anticoagulants (DOACs) on comprehensive PAD outcomes warrants further study. Hypothesis: Anticoagulant therapy, particularly DOACs, improves CV outcomes in PAD. Methods: We conducted a retrospective study of patients who underwent ankle-brachial index testing (ABI) from 1996 – 2020 at Mayo Clinic. We included patients with PAD defined by abnormal ABI (/=1.4). Prolonged (>6 months) DOAC or warfarin use was compared to no anticoagulant therapy. Multivariable (MV) regression, controlling for baseline CV risk factors, was used. Results: 21,891 patients had abnormal ABI readings; 3,093 were on warfarin and 267 were on DOAC for any indication. Anticoagulation improved mortality, with DOACs superior to warfarin. DOACs improved critical limb ischemia (CLI)/amputation in univariate analysis, although this was not significant in MV. Patients with poorly compressible vessels (ABI >/=1.4) had increased limb outcomes compared to reduced ABI ( Conclusion: Anticoagulant therapy improved mortality in a large cohort of PAD patients. The risk of limb events appears improved in those on DOACs. DOACs showed improved risk profiles compared to warfarin regarding CV and bleeding outcomes.

OBJECTIVE. The purpose of this study is to report the frequency of major bleeding after percutaneous image-guided core biopsy and its association with aspirin usage and duration of prebiopsy aspiri...

Context Peripheral artery disease (PAD) is highly prevalent in the general population, affecting up to 25% of patients 55 years of age or older. There is a known association with acute ischemic stroke, but limited large cohort studies exist pertaining to the relationship between PAD severity and incident ischemic stroke. Objectives To evaluate the risk of incident ischemic stroke and mortality along the spectrum of low and elevated ankle brachial index (ABI) measurement. Methods We performed a retrospective extraction of ABI data of all adult patients who underwent lower extremity physiology study for any indication from January 1, 1996 to June 30, 2018 in the Mayo Clinic health system. PAD was categorized into severe, moderate, mild, and borderline based on ABI measurements and poorly compressible arteries (PCA). These were compared with normal ABI measurements. Associations of PAD/PCA with new ischemic stroke events and all cause mortality were analyzed. Hazard ratios (HR) were calculated using multivariable Cox proportional regression with 95% confidence intervals. Results A total of 39,834 unique patients were included with a median follow up duration of 4.59 years. All abnormal ABI groups, except borderline PAD, were associated with increased risk of incident ischemic stroke after multivariate regression compared to normal ABI. A severity-dependent association was observed between PAD and ischemic stroke with moderate (HR, 1.22 [95% CI, 1.10–1.35]) and severe (HR, 1.19 [95% CI, 1.02–1.40]) categories conferring similar risk in comparison to normal ABI. Patients with PCA carried the greatest ischemic stroke risk (HR, 1.30 [95% CI, 1.15–1.46]). Similarly, abnormal ABI groups were associated with a significant risk for all cause mortality in a severity-dependent manner, with severe PAD conferring the greatest risk (HR, 3.07 [95% CI, 2.88–3.27]). Conclusions This study adds to the growing body of evidence that both PAD and PCA are independent risk factors for incident ischemic stroke and all cause mortality. The association of PAD severity and PCA with risk of ischemic stroke may help clinicians with risk stratification and determining treatment intensity.

Introduction Given the potential side effects and the lack of data on its efficacy, the role of statins in the very elderly (age 75+) with peripheral arterial disease (PAD) is uncertain. Previous studies have shown significant mortality benefit in very elderly patients with coronary artery disease, but the effect in PAD has not been evaluated. Methods Very elderly patients aged 75 to 80 with at least five years of follow-up who underwent ankle-brachial index (ABI) measurement were included. PAD was defined as either low ABI 1.40. Demographic, medication use, comorbidity and mortality data was obtained using the electronic medical record. Univariate and multivariate Cox proportional hazard analyses were performed. Results In total, 4,560 very elderly subjects with PAD were included in the analysis. The median age was 77 (interquartile range 76–79) and 39% were female. 3,462 (76%) had low ABI while 1098 (24%) had high ABI. Univariate analysis showed that patients on statins were more likely to be male, have diabetes, have coronary artery disease, and have hyperlipidemia. Overall, 1,355 (30%) patients died in the five-year period. Unadjusted all-cause mortality hazard ratios for patients with low or high ABI with statin use was 0.66 (95% confidence interval [CI]: 0.57–0.75) and 0.80 (95% CI: 0.66–0.97), respectively. After adjusting for age, sex, coronary artery disease and diabetes, statin use in low and high ABI was still associated with significant reductions in risk of all-cause mortality of 0.59 (95% CI: 0.51–0.67) and 0.66 (95% CI: 0.54–0.80), respectively. The survival curve for very elderly patients with PAD by statin use is shown in Figure 1. Conclusion Statin use in the very elderly was associated with lower risk of all-cause mortality in the five-year period after diagnosis of PAD. There appears to be a mortality benefit with statin use in the very elderly with PAD, though careful consideration of benefits and side effects should be individualized in this age group. Figure 1 Funding Acknowledgement Type of funding source: None

Introduction Antiplatelet therapy is the cornerstone of treatment for many atherosclerotic vascular pathologies including peripheral arterial disease (PAD). Patients with PAD often have comorbid conditions that require complex antithrombotic therapy, i.e. combined antiplatelet and anticoagulation. Methods All adult patients undergoing ankle brachial index (ABI) measurements were included in the study. ABI values between 1.00 and 1.40 were considered normal, and values below 1.00 or above 1.40 were considered PAD. Demographic, comorbidity and outcome data were obtained using diagnostic codes from the electronic health record. Three medication classes were analyzed: aspirin, non-aspirin oral antiplatelets (e.g. P2Y12 inhibitors) and oral anticoagulants (warfarin and the direct oral anticoagulants). Medication use was determined for patients who had been on a medication for at least one year. Cox proportional hazard analysis for the time to first bleeding event was analyzed. Bleeding was defined as any bleeding requiring medical evaluation (including clinically-relevant non-major bleeding and major bleeding). Results In all, 40,144 patients were included in the analysis (mean age 66±15, 43% female). Patients with PAD were more likely to be on double therapy (one antiplatelet with anticoagulation) (28% vs 19%) and triple therapy (dual antiplatelet with anticoagulation) (10% vs 4%). Unadjusted hazard ratios for bleeding risk showed increased risk of bleeding for patients with PAD (1.18, 95% confidence interval [CI]: 1.08–1.29), though the association is no longer present after adjustment for antithrombotic therapy. Adjusting for age, sex and PAD class, compared to no antithrombotic therapy, there was increased risk of bleeding for monotherapy (1.91, 95% CI: 1.61–2.26), double therapy (3.40, 95% CI: 2.89–4.00) and triple therapy (5.00, 95% CI: 4.21–5.96). Among medications, aspirin and anticoagulant use was independently associated with the greatest increase in risk of bleeding. Conclusion Patients in PAD are at increased risk of bleeding secondary to antithrombotic therapy. Complex antithrombotic therapy with double or triple therapy confer additional bleeding risk, particularly regimens containing aspirin and oral anticoagulants. Funding Acknowledgement Type of funding source: None

Calf muscle pump (CMP) promotes venous return from the lower extremity and contributes to preload and cardiac output. Impaired CMP function may reflect a measure of frailty or cumulative disease burden or may impede cardiac function. The study objective was to test the hypothesis that impaired CMP negatively impacts survival. Consecutive adult patients who underwent venous strain gauge plethysmography at the Mayo Clinic Gonda Vascular Laboratory (January 1, 1998 – December 31, 2011) were assessed for overall survival. Patients with venous incompetence, venous obstruction or unilateral calf pump dysfunction were excluded. Risk of mortality was assessed with Cox proportional hazard ratios and after adjusting for Charlson Comorbidity Index variables. Over the study period, 2728 patients were included in the analysis. Compared to patients with normal CMP, those with impaired CMP were older ( p < 0.001), predominantly female ( p = 0.01) and had higher mean Charlson scores ( p < 0.001). Patients with impaired CMP had a higher mortality rate at 5 (8.9% vs 2.4%), 10 (17.5% vs 5.9%), and 15 years (22.8% vs 8.3%) compared to those with normal CMP ( p < 0.001 for each comparison). Of patients with heart failure, those with impaired CMP had worse survival at each 5-year increment compared to those with normal CMP ( p < 0.05 at each increment). In conclusion, impaired CMP appears to be an independent predictor of poor outcomes after adjusting for variables within the Charlson Comorbidity Index. The association between impaired CMP, heart failure, and mortality may represent a negative impact on circulatory function or a surrogate measure of frailty.

Context Reduced bone material strength index (BMSi) and increased cortical porosity (CtPo) have emerged as potentially contributing to fracture risk in type 2 diabetes mellitus (T2DM) patients. Objective To determine whether BMSi or CtPo are related to other diabetic complications. Design Cross-sectional observational study. Setting Subjects recruited from a random sample of southeast Minnesota residents. Participants A total of 171 T2DM patients (mean age, 68.8 years) and 108 age-matched nondiabetic controls (mean age, 67.3 years). Main Measures Bone material strength index was measured using microindentation, skin advanced glycation end-products (AGEs) measured using autofluorescence, high-resolution peripheral quantitative computed tomography at the distal radius and tibia, assessment of diabetic microvascular complications including urine microalbuminuria, retinopathy, neuropathy, and vascular disease (ankle brachial index and transcutaneous oxygen tension [TcPO2]). All analyses were adjusted for age, sex, and body mass index. Results Skin AGEs were negatively correlated with the BMSi in both T2DM (r = -0.30, P < 0.001) and control (r = -0.23, P = 0.020) subjects. In relating diabetic complications to CtPo, we found that T2DM patients with clinically significant peripheral vascular disease (TcPO2 ≤ 40 mm Hg) had higher (+21.0%, P = 0.031) CtPo at the distal tibia as compared to controls; in these subjects, CtPo was negatively correlated with TcPO2 at both the distal tibia (r = -0.39, P = 0.041) and radius (r = -0.41, P = 0.029). Conclusions Our findings demonstrate that bone material properties are related to AGE accumulation regardless of diabetes status, while CtPo in T2DM patients is linked to TcPO2, a measure of microvascular blood flow.

Background Ankle‐brachial indexes ( ABI ) are a noninvasive diagnostic tool for peripheral arterial disease and a marker of increased cardiovascular risk. ABI is calculated using the highest systolic blood pressure of the 4 ankle arteries (bilateral dorsalis pedis and posterior tibial). Accordingly, patients may be assigned a normal ABI when the result would be abnormal if calculated using one of the other blood pressure readings. Cardiovascular outcomes for patients with discordant ABI s are undescribed. Methods and Results We performed a retrospective study of patients who underwent ABI measurement for any indication between January 1996 and June 2018. Those with normal ABI s (1.00–1.39) were included. We compared patients with all 4 normal ABI s (calculated using all 4 ankle arteries; n=15 577, median age 64.0 years, 54.4% men) to those with discordant ABI s (at least 1 abnormal ABI ≤0.99; n=2095, median age 66.0 years, 47.8% men). The outcomes assessed were ischemic stroke, myocardial infarction, and all‐cause mortality. Compared with patients with concordant normal ABI s, patients with discordant ABI s were older; women; smoked; and had chronic kidney disease, coronary artery disease, diabetes mellitus, chronic obstructive pulmonary disease, hypertension, or prior stroke. Patients with discordant ABI s had a greater risk of myocardial infarction (hazard ratio [HR], 1.31; 95% CI, 1.10–1.56), ischemic stroke ( HR, 1.53; 95% CI, 1.37–1.72), and all‐cause mortality ( HR, 1.27; 95% CI, 1.16–1.39), including after adjustment for baseline comorbidities. Conclusions Discordant ABI results were associated with an increased risk of myocardial infarction, stroke, and all‐cause mortality in the studied population. Clinicians should examine ABI calculations using all 4 ankle arteries to better characterize a patient's cardiovascular risk.

International audience; Exertional lower limb pain is a frequent diagnostic issue in elderly patients. Arterial claudication results from the mismatch between the oxygen requirement of, and oxygen delivery to the exercising muscles. Non-invasive vascular investigations (ultrasound imaging, plethysmography or segmental pressure) are used in routine at rest or following exercise, but none can be used during walking or to directly monitor cutaneous oxygen delivery to the limb. Here, we review the methods, tips and traps of the transcutaneous oxygen pressure measurement technique and potential applications.Transcutaneous oxygen pressure measurement is largely used in vascular medicine for patients with critical limb ischemia. It can also detect regional blood flow impairment at the proximal and distal limb simultaneously and bilaterally during exercise. Exercise-oximetry can also analyze systemic oxygen pressure changes on a reference area on the chest, to screen for occult pulmonary disease. As a surface technique, it does not directly measure muscle oxygen content but provides a reliable estimation of regional blood flow impairment.With the use of a recently reported index that is independent of the unknown transcutaneous gradient for oxygen, exercise-oximetry provides some accurate information compared to classical non-invasive vascular investigations to argue for a vascular or non-vascular origin of exertional lower limb pain during exercise. Although a time consuming technique, it is a simple test and it is progressively spreading among referral vascular centers as a useful non-invasive diagnostic tool for patients suspected of arterial claudication.

Patients with end-stage renal disease undergoing kidney transplant often have diffuse atherosclerosis and high cardiovascular morbidity and mortality rates. We analyzed the correlation of peripheral arterial disease (PAD), here quantified by an abnormal ankle–brachial index (ABI) measured within the 5 years prior to kidney transplant, with graft failure and mortality rates (primary end points) after adjusting for known cardiovascular risk factors (age, sex, smoking history, hypertension, diabetes, stroke, known coronary artery disease or heart failure, years of dialysis). Of 1055 patients in our transplant population, 819 had arterial studies within the 5 years prior to transplant. Secondary end points included myocardial infarction; cerebrovascular accident; and limb ischemia, gangrene, or amputation. Low ABI was an independent and significant predictor of organ failure (OR, 2.77 (95% CI, 1.68–4.58), p

Introduction Lower extremity physiologic studies are an important non-invasive diagnostic tool in peripheral arterial disease (PAD). PAD and atrial fibrillation (AF) are associated with increased cardiovascular and all-cause mortality. Purpose To evaluate the association between PAD and new-onset AF and the risk of stroke. Methods We performed a study of all patients without AF undergoing ankle-brachial index (ABI) for any indication between January 1996 to June 2018. The ABI cut-off were as follows: abnormal ABI (0–0.99), normal ABI (1.00–1.39) and poor vessel compressibility (PC) (1.40+). Demographic, comorbidity, and outcome variables were extracted using the electronic medical record. Results Overall, 34,441 patients (mean age 66.8±14.3, 57.3% male, 88.2% white) were included in the study with a median follow-up of 7.2 years (interquartile range, 3.0–12.9 years). Multivariate Cox proportional hazard analysis showed increased risk of new-onset AF for male sex, older age, hypertension, coronary artery disease, cerebrovascular disease, chronic kidney disease stage III or greater, congestive heart failure, chronic obstructive pulmonary disease, and cancer (all p Conclusion Abnormalities in ABI results, particularly poorly-compressible vessels, are independently associated with new-onset atrial fibrillation in a large ambulatory cohort. While the mechanism cannot be assessed, common inflammatory mechanisms and increased vascular stiffness may play an important role. Identification of AF in these at-risk patients may improve cardiovascular outcomes.

Background Peripheral arterial disease is a marker of aggressive atherosclerosis. The ankle brachial index (ABI) is a simple and non-invasive tool to diagnose peripheral arterial disease (PAD). Patients with PAD are at increased risk for ischemic strokes and other cardiovascular diseases. Purpose To evaluate the association of abnormal ABI and poorly compressible vessels with ischemic stroke in a large patient cohort. Methods We analyzed lower extremity vascular studies of all patients with ABI measurements at a tertiary care hospital between January 1996 and August 2018. PAD is defined as ABI1.4 while ABI between 1.0–1.4 is normal. Association of these ABIs with new ischemic stroke events post ABI measurement were analyzed after adjusting for high risk confounders such as atrial fibrillation. Hazard ratios (HR) were calculated using multivariable Cox proportional regression with 95% confidence intervals. Results In total, 38,016 unique patients (mean age 66.1±14.8 years, female 42.3%) were included. Abnormal ABI was found to be more prevalent among elderly male patients compared to patients with normal ABI. In contrast to non-PAD patients, both PAD and PC/NC patients as defined by ABI had a statistically significant risk of ischemic stroke, with PAD conferring the greatest risk compared to PC/NC vessels. The data is summarized in Table 1. Table 1 Unadjusted HR p-value Adjusted HR p-value PAD vs. No PAD 2.77 (2.62, 2.92) Conclusion This study adds to the growing body of evidence that PAD and poorly-compressible vessels are independently associated with an increased risk of ischemic stroke. Given the associated risk of cerebrovascular disease, clinicians should aggressively treat to minimize risk factors in those with abnormal ABIs.

Peri-procedural anticoagulant management hinges on the balance of hemorrhagic and thrombotic complications. The radiologist is tasked with accurately assessing the hemorrhagic risk for patients undergoing procedures, taking into account procedural bleeding rates, underlying coagulopathy based on lab tests, and use of anticoagulants. The purpose of this article is to provide a contemporary review of commonly used anticoagulants and, incorporating published evidence, review their management related to image-guided procedures.

Purpose To report incidence of bleeding after image-guided percutaneous core needle biopsy performed in patients taking clopidogrel within 5 days. Materials and Methods This was a retrospective review of image-guided percutaneous core needle biopsies performed in patients with clopidogrel use within 5 days of the procedure between January 2002 and November 2014. Data including biopsy site, needle size, number of samples, and serum coagulation studies were collected. Routine follow-up of patients was performed 24–72 hours after biopsy. Major bleeding complications were defined as grade 3 or greater using Common Terminology Criteria for Adverse Events. There were 63 deep biopsies performed in 63 patients with recent use of clopidogrel. Mean time of clopidogrel abstinence before biopsy was 2.9 days ± 1.9 (median 3 days). Clopidogrel had been taken within 24 hours of the biopsy by 12 patients. There were 48 patients (76%) who also took aspirin within 5 days of the procedure. The most common procedure was liver biopsy (21/63; 33%), followed by lung (12/63; 19%), abdominal/pelvic/retroperitoneal mass (12/63; 19%), and renal (11/63; 17%) biopsies. Results A major bleeding complication (1/63; 1.6%) occurred after injury to an intercostal artery during lung biopsy, which was successfully treated with coil embolization. No minor bleeding complications were identified. Conclusions In this study comprising a small number of patients undergoing various biopsy procedures, recent clopidogrel use was associated with a very low incidence of major bleeding.

Heart Failure (HF) and Peripheral Arterial Disease (PAD) share common risk factors, such as diabetes and smoking. PAD is an independent predictor of mortality in patients with HF. There is regional variability in the recommendation for screening patients with PAD for HF. We examined the incidence of

Objective To quantify compliance with guideline recommendations for secondary prevention in peripheral artery disease (PAD) using natural language processing (NLP) tools deployed to an electronic health record (EHR) and investigate provider opinions regarding clinical decision support (CDS) to promote improved implementation of these strategies. Patients and Methods Natural language processing was used for automated identification of moderate to severe PAD cases from narrative clinical notes of an EHR of patients seen in consultation from May 13, 2015, to July 27, 2015. Guideline-recommended strategies assessed within 6 months of PAD diagnosis included therapy with statins, antiplatelet agents, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and smoking abstention. Subsequently, a provider survey was used to assess provider knowledge regarding PAD clinical practice guidelines, comfort in recommending secondary prevention strategies, and potential role for CDS. Results Among 73 moderate to severe PAD cases identified by NLP, only 12 (16%) were on 4 guideline-recommended strategies. A total of 207 of 760 (27%) providers responded to the survey; of these 141 (68%) were generalists and 66 (32%) were specialists. Although 183 providers (88%) managed patients with PAD, 51 (25%) indicated they were uncomfortable doing so; 138 providers (67%) favored the development of a CDS system tailored for their practice and 146 (71%) agreed that an automated EHR-derived mortality risk score calculator for patients with PAD would be helpful. Conclusion Natural language processing tools can identify cases from EHRs to support quality metric studies. Findings of this pilot study demonstrate gaps in application of guideline-recommended strategies for secondary risk prevention for patients with moderate to severe PAD. Providers strongly support the development of CDS systems tailored to assist them in providing evidence-based care to patients with PAD at the point of care.

Background: We evaluated the role of increased cardiac troponin T (cTnT), vascular, and cardiac diseases in predicting 5 and 10-year all-cause mortality after kidney transplantation. Methods: We reviewed a cohort of 764 kidney transplant recipients and analyzed pertinent cardiovascular risk factors at the time of transplant evaluation. Proportional hazards regression analysis with bootstrapping method was utilized to provide a risk stratification score for mortality. Results: Mean age was 58.8 years (SD 12.1) and median follow-up was 7.0 years (range 1 day to 18.0 years). Fifty-four percent of patients (n = 415) had cTnT measured (median 0.02 ng/mL, range 0.01–4.91). Fifty-three percent (n = 407) had vascular disease, 59% (n = 448) had diabetes, and 44% (n = 336) had cardiac disease pre-transplant. Sixty percent (n = 460) required dialysis. Older age, increased cTnT, pre-transplant vascular and cardiac diseases predicted mortality in multivariate analysis. We derived 2 scoring systems with and without cTnT – the ACV and ACTV scores (age, cardiac disease, elevated cTnT, and vascular disease) – as predictors of mortality after kidney transplant. Point assignments were: age 60–69 years (1), age ≥70 years (2), cardiac disease (1), cTnT ≥0.04 ng/mL (1), and vascular disease (1). Both scoring systems significantly predicted mortality. The ACTV score better delineated risk stratification across score levels (0–2, 3–4, and 5 points). Conclusions: We developed a risk schema predictive of all-cause mortality after kidney transplant in a derivation cohort. The ACTV score, including an elevated cTnT, provided superior prediction compared to a scoring system without cTnT. Further studies to validate these findings are needed.

Introduction: Peripheral arterial disease (PAD) is a strong predictor of systemic atherosclerosis with substantial morbidity and mortality. Medical management in PAD and coronary artery disease (CAD) has changed in recent eras with the use of high intensity statin and dual antiplatelet therapies. Hypothesis: Test whether mortality and major adverse cardiovascular events (MACE) (death and MI) has decreased over eras among PAD patients undergoning revascularization with percutaneous coronary intervention (PCI). Methods: Longitudinal cohort study of 549 patients who underwent PCI and non-invasive lower arterial study between 1997 and 2008 as identified in the Mayo Clinic PCI registry were stratified into 2 time eras: 1997-2003 (era1), and 2004-2008 (era2). PAD was assessed using the highest resting ABI and stratified according to established categories; < 0.90 (definite PAD); 1.00-1.39 (normal); and ≥ 1.40 defined a non-compressible artery. Kaplan-Meier methods were used to analyze follow-up survival. Results: Stratified by ABI over both time eras, 225 patients had PAD, 94 were non-compressible, and 142 were normal. Overall mortality rates were higher in era2 non-compressible and PAD patients than in non-PAD patients when compared to era1 (58%, 33%, 26%, vs 49% 32%, 19%, p Conclusions: Over the past two eras, the overall mortality has increased among patients with PAD and non-compressible vessels in era2 vs. era1 despite higher utilization of statin and antiplatelet therapies.

Lower extremity physiologic testing also known as ankle-brachial indices (ABIs) are an important non-invasive diagnostic tool for peripheral arterial disease (PAD) and a risk marker for cardiovascular outcome. ABI is calculated by adapting the highest systolic blood pressure of the dorsalis pedis or

How best to approach a patient with peripheral arterial disease (PAD) can be an intimidating and confusing task. There are few disease processes as variable in location, presentation, and severity as those seen in the vasculopath. There are many etiologies to be considered simultaneously. Ironically, it is the variability of PAD that provides an opportunity to extract a comprehensive and tightly integrated history and physical examination that is nearly unparalleled in medicine. Similarly, there are few disease processes that offer the opportunity to impact so many aspects of the patient, literally from head to toe. This article, part of a series on PAD, focuses on the initial assessment and evaluation of the PAD, with pathophysiology, genetics, and treatment addressed in accompanying articles. Each patient with PAD is unique (Table 1). Even though the pathophysiology, risk factors, location, and eventual treatment options for a patient often prove routine, the manner in which the patient presents is anything but predictable.1 We have all had the experience of taking a well-structured history (Table 2) from a textbook patient, presented to an attending physician or a colleague, and then watched and listened in disbelief as the confirmatory history is nothing at all similar to what was heard 15 minutes earlier. Unfortunately, patients do not often read the textbook. As demonstrated by McDermott and colleagues,2 the discomfort caused by PAD is more often atypical than typical. Descriptions such as “tired,” “giving way,” “sore,” and “hurts” are offered more often than “cramp.” This forces the healthcare provider to meticulously clarify the location, quality, and circumstances of the discomfort. It is not unusual that a patient reports ≥2 types and locations of discomfort. Careful consideration for pain from both orthopedic and neurogenic sources must be taken. Each symptom should be individually addressed and clarified. These …

Key Points Question Are ankle-brachial indices associated with limb outcomes in community-dwelling patients with peripheral artery disease as identified by computational approaches applied to electronic health records? Findings In this cohort study of 1413 community-dwelling patients, peripheral artery disease was identified and limb outcomes were retrieved by computational approaches applied to electronic health records. Ankle-brachial indices of 1.4 or greater were associated with limb amputation and ankle-brachial indices less than 0.5 were associated with limb revascularization. Meaning Severe disease and poorly compressible arteries detected by ankle-brachial indices were associated with adverse outcomes in community-dwelling patients with peripheral artery disease; ascertainment of peripheral artery disease phenotypes and outcomes by computational approaches applied to electronic health records is feasible., Importance The prevalence and morbidity of peripheral artery disease (PAD) are high, with limb outcomes including revascularization and amputation. In community-dwelling patients with PAD, the role of noninvasive evaluation for risk assessment and rates of limb outcomes have not been established to date. Objective To evaluate whether ankle-brachial indices are associated with limb outcomes in community-dwelling patients with PAD. Design, Setting, and Participants A population-based, observational, test-based cohort study of patients was performed from January 1, 1998, to December 31, 2014. Data analysis was conducted from July 15 to December 15, 2017. Participants included a community-based cohort of 1413 patients with PAD from Olmsted County, Minnesota, identified by validated algorithms deployed to electronic health records. Automated algorithms identified limb outcomes used to build Cox proportional hazards regression models. Ankle-brachial indices and presence of poorly compressible arteries were electronically identified from digital data sets. Guideline-recommended management strategies within 6 months of diagnosis were also electronically retrieved, including therapy with statins, antiplatelet agents, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, and smoking abstention. Main Outcomes and Measures Ankle-brachial index (index ≤0.9 indicates PAD, This population-based cohort study evaluates whether ankle-brachial indices identified through electronic health records among community-dwelling patients with peripheral artery disease are associated with limb revascularization or amputation.

Lower extremity peripheral artery disease (PAD) is highly prevalent. Prognostic risk models supported by automated data extraction of electronic health records (EHRs) would be useful for management of PAD patients. The records-linkage system of the Rochester Epidemiology Project was used to

Klippel-Trenaunay syndrome (KTS) is a complex congenital anomaly featuring two or more of the following: (1) capillary malformations (port-wine stains), (2) soft tissue or bony hypertrophy (or both), and (3) varicose veins or venous malformations. With the purpose of determining the actual significance of venous impairment in patients with KTS, we quantified the venous valvular competency and calf muscle pump function and examined their effect on clinical severity.Included were patients with near-normal function of affected limb(s) and minimal/small foot hypertrophy. Excluded were those with deep venous hypoplasia, aplasia or thrombosis, lymphedema, limb length discrepancy (2.5 cm), peripheral arterial (ankle-brachial index1.0), or cardiac disease and walking impairment. Venous duplex scanning, ascending venography, magnetic resonance imaging, strain gauge plethysmography, and a bone scanogram were performed. We studied eight men and seven women aged 15 to 51 years (median, 24 years). The KTS involved 17 limbs (unilateral in 13 patients and bilateral in 2). Contralateral limbs in patients with unilateral KTS acted as controls (n = 13). Venous clinical severity was graded according to the CEAP and venous clinical severity score (VCSS), and reflux complexity was classified according to the venous segmental disease score. Outflow obstruction (outflow fraction at 1 and 4 seconds; OF(1) and OF(4), respectively), reflux (venous filling index), calf muscle pump function (ejection fraction), and hypertension (residual volume fraction) were determined in both limbs with strain gauge plethysmography. Data, reported as median and interquartile range, were analyzed with the Mann-Whitney test.Varicose veins or venous malformations occurred in the medial, posterior, or anterolateral limb segments of the ankle (7/17, 7/17, and 9/17), calf (10/17, 8/17, and 12/17), knee (9/17, 8/17, and 8/17), and thigh (10/17, 6/17, and 8/17, respectively). Venous malformations occupied the subcutaneous space (17/17) and extended into the subfascial space in 6 (35.3%) of 17 limbs. Abnormal reflux (0.5 seconds) was distributed in the great (64.7%; 11/17) and small (5.9%; 1/17) saphenous veins and the common femoral (23.5%; 4/17), femoral (41.1%; 7/17), popliteal (29.4%; 5/17), perforator (70.6%; 12/17), and axial calf (35.3%; 6/17) veins. There was no difference in the OF(1) and OF(4) between the affected limbs and the controls. Limbs with KTS had a fivefold greater venous filling index (0.133-0.46 mL . 100 mL(-1) . s(-1); 0.258 mL . 100 mL(-1) . s(-1)) than the controls (0.034-0.055 mL . 100 mL(-1) . s(-1); 0.046 mL . 100 mL(-1) . s(-1); P.0001), and this was linked to a higher venous segmental disease score (3 [2-4] vs 0 [0-1]; P.0001). Limbs with KTS had half the ejection fraction (20.8%; 12.3%-24%) of the controls (39.3%; 30.9%-64.6%) and twice as high a residual venous fraction (77% [69.6%-84.5%] vs 40.9% [20.6%-60%]; both P.004). Patients complained of swelling (100%; 15/15), aching (100%; 15/15), pain (93.3%; 14/15) and heaviness (100%; 15/15), tiredness (66.7%; 10/15), and tightness (33.3%; 5/15) of the limb(s) with KTS. Limbs with KTS had a worse (1) venous clinical severity by 11 VCSS points (11 [8-12] vs 0 [0-1]) and (2) clinical status by 3 CEAP classes (C3 [C3-C4] vs C0 [C0-C2]) than the control limbs (both P.0001).Venous disease in limbs with KTS is a major source of morbidity in affected patients. Limbs with KTS are characterized by complex reflux patterns, severe valvular incompetence, calf muscle pump impairment, and venous hypertension, thus explaining the advanced clinical severity (VCSS) and CEAP grade.

Background —Endothelin-converting enzyme-1 (ECE-1) processes big endothelin-1 (ET-1) to ET-1, a peptide implicated in atheroma formation. ECE-1 exists in 2 isoforms (ECE-1α and ECE-1β), the result of alternative splicing of a common gene. Neutral endopeptidase (NEP) is a genetically distinct metallopeptidase that degrades the natriuretic peptides. These peptides mediate antiproliferative and vasodilating actions. We sought to demonstrate the distribution of the 2 ECE-1 isoforms in experimental atherosclerosis, to determine the effects of chronic NEP-I on plasma cGMP concentrations, vascular wall ECE-1 activity, and ET-1 concentration, and to correlate these actions with atheroma formation. Our hypothesis was that chronic NEP-I, in association with augmented cGMP, would inhibit ECE-1 conversion of big ET-1 to active ET-1, thus reducing tissue ET-1 concentrations and associated atheroma formation. Methods and Results —Cholesterol-fed New Zealand White rabbits (n=8, 1% cholesterol diet) and NEP-I–treated cholesterol-fed New Zealand White rabbits (n=8; candoxatril, 30 mg/kg per day, Pfizer) were euthanized after 8 weeks of feeding. ECE-1α and ECE-1β immunoreactivity was present in the aortas of both groups. Compared with control values, plasma cGMP concentrations were increased (2.8±0.6 versus 8.4±1.2 pmol/mL, P P P P Conclusions —These studies suggest that ECE-1 is present and functionally active in the vascular wall in atherosclerosis. Inhibition of ECE-1 by NEP-I represents a novel approach to interruption of the endothelin system in this cardiovascular disease state.

OBJECTIVES We sought to define the vascular actions of the cardiac hormone brain natriuretic peptide (BNP) on cellular proliferation and cyclic guanosine monophosphate (cGMP) in human aortic vascular smooth muscle cells (HAVSMCs). Secondly, we investigated BNP and acetylcholine (ACh) vasorelaxations in aortic rings from normal and atherosclerotic rabbits in the presence and absence of long-term oral inhibition of neutral endopeptidase (NEP). BACKGROUND The vascular actions of BNP are not well defined, despite the presence of its receptor in vascular smooth muscle and the upregulation of NEP, the ectoenzyme that degrades BNP, in the vascular wall in atherosclerosis. METHODS HAVSMCs stimulated with fetal calf serum (FCS) were pulsed with bromodeoxyuridine (BrdU) with and without BNP. The HAVSMCs were incubated in the presence and absence of BNP to assess cGMP. Vasorelaxations to BNP and ACh were assessed in rings in normal and atherosclerotic rabbits in the presence and absence of long-term oral inhibition of NEP, together with assessment of atheroma formation. RESULTS FCS-stimulated BrdU uptake in HAVSMCs was suppressed with BNP. BNP potentiated cGMP in HAVSMCs. BNP resulted in potent vasorelaxation in normal isolated aortic rings, which were impaired in atherosclerotic versus normal rabbits and preserved with NEP inhibition, which also decreased atheroma formation. Relaxations to ACh, which were also impaired in atherosclerosis, were preserved with inhibition of NEP. CONCLUSIONS We conclude that BNP potently inhibits vascular smooth muscle cell proliferation and potentiates the generation of cGMP. BNP potently relaxes the normal rabbit aorta, and this response is impaired in atherosclerosis but preserved with inhibition of NEP, together with a reduction in atheroma formation and preservation of relaxations to ACh.

Nitric oxide (NO) is an important endothelium-derived relaxing factor that functions via activation of soluble guanylyl cyclase and cGMP generation in vascular smooth muscle. Recently, studies have described the synthesis and secretion of C-type natriuretic peptide (CNP) from endothelial cells. This peptide also mediates relaxation via cGMP but through activation of particulate guanylyl cyclase. We tested the hypothesis that endothelium-dependent relaxations to acetylcholine or bradykinin in isolated canine coronary arteries involve both releases of NO and CNP. Rings of canine coronary arteries were incubated with either inhibitors of NO production ( NG-monomethyl-l-arginine,l-NMMA) or the natriuretic peptide receptor antagonist HS-142-1. CNP caused concentration-dependent relaxations of rings with and without endothelium. These relaxations were attenuated by HS-142-1. Relaxations to acetylcholine and bradykinin were attenuated byl-NMMA alone but not attenuated by HS-142-1 alone. Coinhibition withl-NMMA and HS-142-1 significantly inhibited acetylcholine- and bradykinin-induced relaxation to a magnitude greater than either inhibitor alone. In summary, a novel interaction between the NO and the natriuretic peptide system is demonstrated by increased attenuation of endothelium-dependent relaxations to acetylcholine and bradykinin when both NO synthase and natriuretic peptide receptors are inhibited. These investigations support the concept of release of multiple endothelium-derived factors in response to acetylcholine- and bradykinin-receptor stimulation in endothelial cells, which may include CNP, as well as NO.

Objective To determine whether Dendroaspis natriuretic peptide (DNP), a novel peptide isolated from the venom of the Dendroaspis angusticeps snake that contains a 17-amino acid disulfide ring structure similar to that in atrial, brain, and C-type natriuretic peptides, is present in normal human plasma and myocardium and whether, like the other natriuretic peptides, DNP-Iike immunoreactivity (DNP-LI) is activated in human congestive heart failure (CHF). Material and Methods Circulating DNP-LI was assessed in 19 normal human subjects and 19 patients with CHF (New York Heart Association class III or IV) with a specific and sensitive radioimmunoassay for DNP with no cross-reactivity with the other natriuretic peptides. Immunohistochemical studies that used polyclonal rabbit anti-DNP antiserum were performed on human atrial myocardial tissue obtained from four patients with endstage CHF who were undergoing cardiac transplantation and from three donor hearts at the time of transplantation. Results We report that DNP-LI circulates in normal human plasma and is present in the normal atrial myocardium. In addition, DNP-LI is increased in the plasma of patients with CHF. Conclusion This study demonstrates, for the first time, the presence of a DNP-like peptide in normal human plasma and in the atrial myocardium. Additionally, these studies demonstrate increased plasma DNP-LI in human CHF. These results support the possible existence of an additional new natriuretic peptide in humans, which may have a role in the neurohumoral activation that characterizes human CHF.

Endothelin-1 (ET-1) is a 21-amino-acid local and circulating factor whose plasma concentrations are increased in advanced atherosclerosis. ET-1 is cleaved from a prohormone (big ET-1) by endothelin-converting enzymes (ECEs) into the biologically active mature form which mediates vasoconstriction and cell proliferation. This study was designed to test by immunohistochemistry the hypothesis that ECE is present locally in the neointima of atherosclerotic vessels. Two groups of rabbits, control (n = 6) and cholesterol-fed (1% cholesterol diet for 8 weeks; n = 6) were sacrificed. Aortas were excised and divided for determination of tissue ET-1 concentration by RIA and immunohistochemical analysis of ECE. Vascular wall ET-1 was increased in the atherosclerotic aorta (6.1 +/- 0.8 vs. 9.8 +/- 0.9 pg/mg protein; p0.05), whereas circulating ET-1 concentrations were similar in the two groups (3.8 +/- 0.4 vs. 2.4 +/- 1.4 pg/ml). Immunostaining revealed the presence of ECE in endothelial and vascular smooth-muscle cells of the control group. Enhanced ECE immunoreactivity was present in atherosclerotic aortas, particularly in the neointimal macrophages and smooth-muscle cells. We conclude that local vascular wall, but not circulating ET-1, is increased in early atherosclerosis. In addition, ECE immunoreactivity is increased in early atherosclerosis and may therefore contribute to the generation of local ET-1 in early experimental atherosclerosis. These studies provide important insights into the regulation of ET-1 in early atherosclerosis, which may contribute to the elucidation of factors involved in the progression of atherosclerosis.

Background We investigated whether disease location influences survival in patients with peripheral arterial disease. Methods and Results Patients (n=12 731; mean age, 67.5±12.7 years; 57.4% male) who underwent outpatient noninvasive lower extremity arterial evaluation were followed up for 5.9±3.1 years for all‐cause mortality. Peripheral arterial disease (n=8930) was defined as a resting or postexercise ankle‐brachial index ( ABI ) ≤0.90, and normal ABI (n=3 801) was defined as a resting and postexercise ABI of 1.00 to 1.30. Presence or absence of disease at the proximal location or distal location was determined on the basis of D oppler signals in leg arteries; 42% had no PD or DD , 45% had proximal (14% postexercise PD only), 30% had distal disease, 17% had both proximal and distal disease, 28% had proximal only and 14% had distal only. We performed multivariable logistic regression to identify factors associated with disease location, and C ox proportional hazard regression to assess the respective effects of proximal or distal disease on survival. Older age, male sex, diabetes, heart failure, and critical limb ischemia were associated with distal disease, whereas female sex, smoking, hypertension, dyslipidemia, coronary heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, and critical limb ischemia were associated with proximal disease. Over a mean follow‐up of 5.9±3.1 years, 3039 patients (23.9%) died. After adjustment for potential confounders, the hazard ratios ( HR s) of death associated with PD only and DD only were 1.3 (1.3 to 1.4) and 1.5 (1.4 to 1.6), respectively. After additional adjustment for resting ABI , there was no significant association between proximal disease and death, whereas the association of distal disease with death remained significant ( HR , 1.2; 95% CI , 1.1 to 1.3). Conclusions In patients with peripheral arterial disease, proximal and distal disease locations were associated with distinctive risk factor and comorbidity profiles. Distal disease was associated with worse survival even after adjustment for risk factors, comorbidities, and resting ABI .

ObjectiveThis study was conducted to determine the sensitivity and specificity of laser Doppler flowmetry (LDF) measurements for digital obstructive arterial disease (DOAD) using angiography as the reference standard and to compare the accuracy of different classical tests used to assess DOAD. Diagnosis of vascular abnormalities at the digital level is challenging. Angiography is the gold standard for assessment of DOAD but is invasive and expensive to perform.MethodsWe performed a retrospective analysis of consecutive patients referred at Mayo Clinic (Rochester, Minn) for upper extremity arterial assessment during a 27-month period. Finger-brachial index, skin blood flow (in arbitrary units [a.u.]), and skin temperature (in degrees Celsius) were recorded in each digit on the pulp at baseline and after a thermal challenge test (hand placed in a thermal box at 47.0°C for 15 minutes). Angiogram analysis was blinded and performed by a radiologist using a vascularization scale ranging from 0 (no vessel) to 4 (normal). The receiver operating characteristic curve was used to define a specific cutoff point to detect DOAD. Twenty-two patients had LDF measurements and complete angiograms.ResultsA total of 185 digits were analyzed because some patients had only analysis of one hand. The best area under the curve (AUC) was 0.98 (range, 0.94-0.99) for postwarming skin blood flow, with a cutoff point of ≤206 a.u. This AUC was statistically different from AUCs of all the other tests (P < .01). Sensitivity and specificity were 93% (95% confidence interval, 85%-97%) and 96% (95% confidence interval, 90%-99%), respectively.ConclusionsLDF combined with a thermal challenge is highly accurate, safe, and noninvasive means to detect DOAD.

External iliac artery endofibrosis describes an intimal subendothelial fibrosis leading to wall thickening and stenosis that has been described in high-performance athletes. There are anatomical, mechanical, and probably metabolic factors that may contribute to this pathology. Ankle–brachial index (ABI) measurement with exercise testing, duplex ultrasound, computed tomography (CT) or magnetic resonance (MR) angiogram, and ultimately arteriography help to make the diagnosis. Management can be conservative, but most cases require surgical intervention. External iliac vein stenosis and thrombosis in cyclists has rarely been described in the literature. We report a case of extensive left lower limb deep venous thrombosis (DVT) including the external iliac vein diagnosed in a 57-year-old athletic cyclist with a history of external iliac artery thrombosis.

Background With currently available effective interventional methods to treat superficial venous insufficiency, it becomes particularly important to have a simple and reliable method to evaluate the location and severity of venous reflux. To date, there are few studies that evaluated plethysmography with and without tourniquet application to differentiate superficial from deep venous incompetence. Objectives To determine if strain gauge plethysmography (SGP) with and without tourniquet application can be used to distinguish between the superficial and deep venous components of venous incompetence. Methods We conducted a prospective study using SGP with and without tourniquet application and duplex ultrasound (duplex US) to assess the severity and location of venous incompetence in 62 patients (85 limbs, 42 women, with an age range of 32–81 years) referred to our vascular laboratory for haemodynamic evaluation. Based on duplex US results, patients were diagnosed with superficial (SVI), deep and superficial (mixed) and deep vein incompetence (DVI). Results Mixed incompetence was the most common type. Twenty-three out of 33 limbs in the SVI group normalized their refill rate (RR) with tourniquet application (69.6%). Normalization of the RR with tourniquet application was less common in the mixed ( n: 17 out of 40, 42.5%) and DVI ( n: 2 out of 6, 33.3%) groups. Conclusion SGP with tourniquet application is a simple and fast technique that can identify patients with SVI, based on RR improvement, who probably would benefit more from ablation procedures. Further studies evaluating impact of SGP with tourniquet test results on clinical outcome of SVI invasive treatment are warranted

Objectifs Determiner la sensibilite et la specificite de la mesure laser Doppler pour la detection des arteriopathies digitales obstructives en utilisant l’arteriographie comme mesure de reference. Comparer ces resultats a ceux obtenus par d’autres tests. Le diagnostic d’arteriopathie digitale est difficile. L’arteriographie est le test de reference mais celui-ci est invasif et onereux. Methode Une etude retrospective de patients consecutivement admis a la Mayo Clinic (Rochester, MN, USA) pour une exploration arterielle des membres superieurs a ete realisee. L’index doigt-bras, la mesure de flux cutane (en unite arbitraire ; u.a.), la temperature cutanee (en °C) ont ete mesures sur chaque doigt au niveau de la pulpe au repos puis apres un chauffage local (mains placees dans une boite chauffante a 47 °C pendant 15 minutes). L’arteriographie analysee en aveugle a ete realisee par un radiologue en utilisant une echelle de vascularisation cotee entre 0 (aucun vaisseau) et 4 (normal). Les courbes Receiver Operating Characteristic (ROC) ont ete utilisees pour definir le seuil permettant de detecter l’arteriopathie digitale obstructive. Vingt-deux patients ont ete analyses. Resultats Un total de 185 doigts a ete analyse. Pour certains patients, une seule main etait analysee. La meilleure aire sous la courbe (AUC) etait de 0,98 [0,94–0,99] pour le flux laser cutane apres chauffage avec une valeur seuil ≤ 206 u.a. Cette AUC etait statistiquement differente de celle des autres tests. La sensibilite et la specificite etaient de 93 % (intervalle de confiance a 95 %, 85 %–97 %) et 96 % (intervalle de confiance a 95 %, 90 %–99 %). Conclusion Le laser combine au chauffage local est un outil sur, non invasif et performant pour detecter l’arteriopathie digitale obstructive.

Stent therapy has been proposed as an effective treatment of chronic iliofemoral (I-F) and inferior vena cava (IVC) thrombosis. The purpose of this study was to determine the effects of technically successful stenting in consecutive patients with advanced CVD (CEAP3-6 +/- venous claudication) for chronic obliteration of the I-F (+/-IVC) trunks, on the venous hemodynamics of the limb, the walking capacity, and the clinical status of CVD. These patients had previously failed to improve with conservative treatment entailing compression and/or wound care for at least 12 months.The presence of venous claudication was assessed byor =3 independent examiners. The CEAP clinical classification was used to determine the severity of CVD. Outflow obstruction [Outflow Fraction at 1- and 4-second (OF1 and OF4) in %], venous reflux [Venous Filling Index (VFI) in mL/100 mL/s], calf muscle pump function [Ejection Fraction (EF) in %] and hypertension [Residual Venous Fraction (RVF) in %], were examined before and after successful venous stenting in 16 patients (23 limbs), 6 females, 10 males, median age 42 years; range, 31-77 yearas, left/right limbs 14/9, using strain gauge plethysmography; 7/16 of these had thrombosis extending to the IVC. Contralateral limbs to those stented without prior I-F +/- IVC thrombosis, nor infrainguinal clots on duplex, were used as control limbs (n = 9). Excluded were patients with stent occlusion or stenoses, peripheral arterial disease (ABI1.0), symptomatic cardiac disease, unrelated causes of walking impairment, and malignancy. Preinterventional data (or =30 days) were compared with those after endovascular therapy (8.4 months; interquartile range [IQR], 3-11.8 months). Nonparametric analysis was applied.Compared with the control group, limbs with I-F +/- IVC thrombosis before stenting had reduced venous outflow (OF4) and calf muscle pump function (EF), worse CEAP clinical class, and increased RVF (all, P0.05). At 8.4 months (IQR, 3-11.8 months) after successful I-F (+/-IVC) stenting, venous outflow (OF1, OF4) and calf muscle pump function (EF) had both improved (P0.001) and the RVF had decreased (P0.001), at the expense of venous reflux, which had increased further (increase of median VFI by 24%; P = 0.002); the CEAP status had also improved (P0.05) from a median class C3 (range, C3-C6; IQR, C3-C5) [distribution, C6: 6; C4: 4; C3: 13] before intervention to C2 (range, C2-C6; IQR, C2-C4.5) [distribution, C6: 1; C5: 5; C4: 4; C2: 13] after intervention. At this follow up (8.4 months median), venous outflow (OF1, OF4), calf muscle pump function (EF), and RVF of the stented limbs did not differ significantly from those of the control; significantly worse (P0.025) were the amount of venous reflux (VFI), and the CEAP clinical class, despite the improvement with stenting. Incapacitating venous claudication noted in 62.5% (10 of 16, 95% CI, 35.8%-89.1%) of patients (15 of 23 limbs; 65.2%, 95% CI, 44.2%-86.3%) before stenting was eliminated in all after stenting (P0.001).Successful I-F (+/-IVC) stenting in limbs with venous outflow obstruction and complicated CVD (C3-C6) ameliorates venous claudication, normalizes outflow, and enhances calf muscle pump function, compounded by a significant clinical improvement of CVD. The significant increase in the amount of venous reflux of the stented limbs indicates that elastic or inelastic compression support of the successfully stented limbs would be pivotal in preventing disease progression.

Aneurysms of the aorta, both in the thorax and abdominal segments, have been well studied. This is in part due to relatively easy access for examination, the high rate of incidence, and noninvasive imaging techniques that are readily available in most places. There is little data on systemic arterial aneurysm incidence, natural history or treatment that was obtained in a prospective or randomized method. In sharp contrast, systemic aneurysms are for the most part rare and therefore less likely to be imaged, let alone studied.1 The literature available is primarily retrospective series, literature reviews, and case reports. While accurate and well written, a great many questions are left open for systematic study. With these limitations in mind, this chapter should be read critically and applied to patient care with conservative creativity

A 75-year-old woman presented to the Vascular Medicine Clinic at Mayo Clinic in Rochester (Minnesota, USA) after experiencing an approximately two-month history of progressive shortness of breath on exertion. She denied any history of orthopnea, paroxysmal nocturnal dyspnea, chest pain or lower extremity edema. Her medical history included hyper-parathyroidism, for which she underwent parathyroidectomy, longstanding systemic hypertension, hyperlipidemia and obesity. A physical examination revealed that the patient was comfortable and in no distress at rest. Her blood pressure level was 148/90 mmHg, and her heart rate was 90 beats/min and regular. Neck examination revealed a jugular venous pressure of 10 cmH2O with a prominent V wave. Palpation of the precordium revealed a right ventricular heave. A systolic murmur was noted at the right upper sternal border that varied with inspiration. She had a pulsatile liver, mild ascites and systolic bruits over both kidneys, with the diastolic component on the left side. Findings on the rest of her physical examination were unremarkable. Laboratory studies revealed a creatinine level of 2.3 mg/dL. A chest x-ray revealed cardiomegaly, right ventricular enlargement, a prominent right hilum and pulmonary vascular congestion. An electrocardiogram revealed atrial tachycardia with variable atrioventricular block at a heart rate of 105 beats/min, premature ventricular complexes, right ventricular bundle branch block and left anterior fascicular block. An echocardiogram revealed severe biatrial enlargement, mild left ventricular enlargement with restrictive hemodynamics and an ejection fraction of 56%, mild right ventricular enlargement with severe tricuspid valve regurgitation, and an estimated right ventricular systolic pressure of 61 mmHg. An abdominal computed tomography angiogram revealed a single left renal artery that branched to the upper pole, with a 3.2 cm × 2.5 cm calcified aneurysm and mural thrombus coursing inferiorly (Figure 1). The aneurysm communicated with an enlarged left renal vein. The right renal artery also had a 4.5 cm aneurysm at the lower pole, in direct communication with the markedly dilated right renal vein. The anterior and posterior right renal veins were enlarged and involved with the arteriovenous malformation (AVM). The appearance and rate of contrast mixing in the renal artery and vein in these AVMs suggested high-volume left-to-right shunts that were likely congenital in origin (Figure 2). A technetium-99m mercaptoacetyltriglycine renal scan showed 51% function of the right and 49% function of the left kidney, suggesting an equal contribution to renal function by each kidney. Other causes of cardiomyopathy were excluded. Further inquiry revealed a history of an abdominal bruit in 1970, at which time an arteriogram revealed bilateral congenital renal AVMs. Figure 1) Aneurysmal changes with calcification of the wall of the arteriovenous malformations (arrows) Figure 2) Reconstructed images showing bilateral arteriovenous malformations Right heart catheterization showed a systolic/diastolic/ mean pulmonary artery (PA) pressure of 54/24/36 mmHg, mean right atrial pressure of 14 mmHg and a PA wedge pressure of 16 mmHg. Thermodilution cardiac output was increased at 9.9 L/min, with a cardiac index of 4.58 L/min/m2. Mean PA resistance was 7.63 Wood units/m2, arterial oxygen saturation was 90% and PA oxygen saturation was 76% (Table 1). After 9 ng/kg/min prostacyclin infusion, the patient’s mean PA pressure decreased to 29 mmHg, cardiac output increased to 13.3 L/min, and her PA resistance decreased to 4.69 Wood units/m2. TABLE 1 Right heart catheterization Consideration was given to nephrectomy in an attempt to relieve the left-to-right shunt; however, given the bilateral AVMs occupying a large area of renal parenchyma, it was not attempted because of the risk of dialysis. The patient underwent successful coil embolization of the left renal AVM, eliminating the left-to-right shunt and improving renal perfusion. The patient’s creatinine improved to 1.3 mg/dL, tricuspid regurgitation decreased and functional capacity improved following coil embolization (Figure 3). These benefits were sustained one year after treatment. Figure 3) Arteriogram before and after coil embolization of the arteriovenous malformation

Although previous studies have suggested that aging results in an increase in vascular stiffness, diseases that increase in prevalence with advanced age may have confounded the results of some of this past research. The purpose of this investigation was to determine whether aging per se results in reduced arterial compliance by using animals that are resistant to atherosclerosis and do not develop hypertension or hyperlipidemias with advanced age. We evaluated systemic and regional (femoral) arterial compliance in older (110 ± 8 months old) and in younger (27 ± 2 months old) female beagle dogs by using a computer-based assessment of the diastolic decay of arterial pressure waveforms and a modified Windkessel model of the circulation. Although systemic arterial pressure was very similar in both age groups, cardiac output was 29% lower ( p = 0.03) and systemic vascular resistance was 24% higher ( p = 0.02) in the older dogs. Moreover, there was an age-related reduction in systemic arterial compliance, derived both from the exponential decay in the arterial pulse (C 1 ) ( p = 0.05) and that derived from the oscillatory component of the diastolic pulse wave (C 2 ) ( p = 0.04). By contrast, although femoral vascular resistance was 25% higher in the older dogs ( p = 0.04), regional (femoral) vascular compliance measured after femoral arterial occlusion was also 25% reduced but was not significantly changed with age ( p = 0.14). These results demonstrate that systemic arterial compliance is reduced with age in dogs, extending this finding to animals without age-related diseases that frequently occur in older human beings. Regional compliance, evaluated in the isolated femoral vascular bed, also tends to be reduced with age, but variability in this parameter in dogs reduces the significance of this finding.

1. While the natriuretic peptides (atrial, brain and C-type) mediate potent endothelium-independent vasorelaxing actions in vitro, the role of the endogenous natriuretic peptide system in vascular regulation in vivo remains unclear. 2. HS-142-1 is a novel natriuretic peptide receptor antagonist derived from a fungus named Aureobasidium sp. which selectively blocks particulate guanylate cyclase-linked natriuretic peptide A and B receptors that bind atrial, brain and C-type natriuretic peptide, and thus attenuates the generation of cGMP. 3. To characterize the vascular actions of the endogenous natriuretic peptide system in the control of basal coronary and systemic haemodynamics, six normal male mongrel anaesthetized dogs were studied while a second group of five dogs served as a control. HS-142-1 was given as an intravenous bolus at 3 mg/kg and was studied over five 20 min periods. 4. No significant difference after HS-142-1 was observed in mean arterial pressure, heart rate, cardiac output, right atrial pressure, pulmonary capillary wedge pressure or systemic vascular resistance compared with control. In contrast, a significant increase in coronary vascular resistance and decrease in coronary blood flow were observed which were different from the baseline values and the responses of the control group. 5. These studies demonstrate that HS-142-1 produces vasoconstriction in the coronary circulation. We conclude that the endogenous natriuretic peptide system, which is of cardiac and endothelial cell origin, is an important regulator of basal coronary vascular tone.