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Background: There are limited data on differences in angiographic distribution of peripheral artery disease and endovascular revascularization strategies in patients presenting with intermittent claudication (IC) and critical limb ischemia (CLI). We aimed to compare anatomic features, treatment strategies, and clinical outcomes between patients with IC and CLI undergoing endovascular revascularization. Methods: We examined 3326 patients enrolled in the Excellence in Peripheral Artery Disease registry from 2006 to 2019 who were referred for endovascular intervention for IC (n=1983) or CLI (n=1343). The primary outcome was 1-year major adverse limb events, which included death, repeat target limb revascularization, or target limb amputation. Results: Patients with CLI were older and more likely to have diabetes and chronic kidney disease and less likely to receive optimal medical therapy compared with IC. Patients with IC had higher femoropopliteal artery interventions (IC 87% versus CLI 65%; P P P P P P =0.014). Major adverse limb event rates for patients with IC and CLI were 16% and 26%, respectively ( P Conclusions: Patients with IC and CLI have significant anatomic, lesion, and treatment differences with significantly higher mortality and adverse limb outcomes in CLI. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01904851. Graphic Abstract: A graphic abstract is available for this article.

OBJECTIVES: The purpose of the present study was to define clinical outcomes of chronic kidney disease (CKD) patients undergoing endovascular revascularization of infrainguinal peripheral artery disease (PAD). BACKGROUND: CKD is an established predictor of advanced PAD. However, clinical outcomes for these patients following endovascular revascularization remain inadequately defined. METHODS: Using the ongoing multicenter Excellence in Peripheral Artery Disease (XLPAD) registry (NCT01904851), we analyzed all-cause death, target limb amputation, and need for repeat revascularization for patients with and without CKD undergoing infrainguinal endovascular revascularization between the years 2005 and 2018. RESULTS: Of 3,699 patients, 15.1% (n = 559) had baseline CKD. CKD patients had significantly higher incidence of heavily calcified lesions (48.4% vs. 38.1%, p < .001) and diffuse disease (66.9% vs. 61.5%, p = .007). Kaplan-Meier analysis showed significant differences between CKD and non-CKD patient outcomes at 12 months for freedom from target limb amputation (79.9% vs. 92.7%, p < .001) and all-cause death (90.1% vs. 97.6%, p < .001). However, freedom from target vessel revascularization was similar between the groups. After adjusting for baseline comorbidities in the CKD and non-CKD groups, the hazard ratios for target limb amputation and death at 12 months were 2.28 (95% confidence interval or CI 1.25-4.17, p < .001) and 4.38 (95% CI 2.58-7.45, p < .001), respectively. CONCLUSIONS: Following endovascular revascularization for infrainguinal PAD, CKD was an independent predictor of all-cause death and target limb amputation at 12 months.

Background: NHLBI supported Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial (TOPCAT) (NCT00094302) investigated whether treatment with spironolactone reduces hospitalization due to heart failure (hHF) in 3,445 adults with prior heart failure and a left ventricular ejection fraction over 45%. We reused publicly available individual patient-level data from NHLBI Data Repository (BioLINCC) to perform hypothesis-generating secondary analyses by machine learning (ML) on the American TOPCAT cohort (n=1767) to identify gender and age groups specific baseline (bl) predictors of hHF. Methods: The subjects were stratified into subgroups based on gender (male and female) and age (50-59, 60-69, 70-79, 80-90). Random Survival Forest (RSF), a non-parametric ML approach, evaluated 172 bl variables as predictors of hHF. Top 10 predictors were subsequently included in a multivariate Cox proportional hazards model. Results: The top 10 predictors of hHF are shown in Figure 1. Overall, renal and hematological biomarkers appeared prominently in the top 10 predictors for these patients. While liver markers were among top predictors for hHF in males, diabetes treatment and diabetic complications were top predictors for females. Also, diabetic treatment was a top predictor among age group 50-59, diabetic complications were top predictors among age groups 50-59 and 70-79, liver markers were top predictors among age groups 70-79, and race and years of smoking were top predictors among age group 60-69. Importantly, the use of potassium sparing diuretic at bl was the top predictor among age group 80-90. Conclusion: Using ML, we uncovered in an unbiased fashion, otherwise overlooked bl predictors of hHF in a large, international, multi-center trial like TOPCAT. Thus, ML can help to identify similarities and differences of disease and treatment outcomes among gender, race, ethnicity, and age specific subgroups and advance precision medicine.

Introduction: The NHLBI supported Systolic Blood Pressure (SBP) Intervention Trial (SPRINT) (NCT01206062) aimed to identify an SBP target to reduce incidence of cardiovascular (CV) morbidity and mortality in hypertensive, non-diabetic patients of age ≥ 50 at increased CV risk. It found that intensive treatment (SBP target Methods: RSF was performed on 30 bl variables from 9361 patients in age group specific cohorts (50-59, 60-69, 70-79, 80-90). The identified top 10 predictors from each cohort were included in a multivariate analysis using a Cox proportional hazards model. Results: The top 10 predictors of ACM for age specific subgroups are shown in Figure 1. As expected, cardiovascular disease (CVD) predictors were selected, yet RSF distinctively identified renal biomarkers as important predictors, consistent with our previous analyses. Smoking status and history of CVD ranked as top predictors among age groups 50-59, 60-69, and 70-79. RSF also identified social factors, including race among age groups 60-69 and 80-90 and female gender among age groups 50-59 and 80-90 as important predictors for ACM. Lipid markers and medications used also showed up as top predictors. Specifically, polypharmacy emerged as a top predictor in age groups 60-69, 70-79, and 80-90, notably ranking higher in the 80-90 age group. Conclusions: Using ML, we uncovered in an unbiased fashion, unanticipated age specific top predictors for ACM in SPRINT trial. This highlights the value of ML for analyzing disease and therapeutic intervention outcomes and age specific prognostic factors to advance precision medicine.

Introduction: The NHLBI supported Prevention of Events with Angiotensin-Converting Enzyme (ACE) Therapy trial (PEACE) (NCT00000558) found that the addition of ACE inhibitor trandolapril to conventional therapy in 8290 patients with stable coronary artery disease and preserved ejection fraction provided no benefit against MACE (cardiovascular death, nonfatal myocardial infarction, or the need for coronary revascularization), the composite primary endpoint. We reused publicly available individual patient-level PEACE data from NHLBI Data Repository (BioLINCC) to perform hypothesis-generating secondary analyses by machine learning (ML) using random survival forest (RSF) to identify gender and age group specific predictors for MACE. Methods: RSF was performed on 50 baseline variables for the MACE outcome in male and female and in age group (69) cohorts. The top ten predictors identified in each cohort were included in a multivariate analysis using a Cox proportional hazards model with a multiple regression approach. Results: The top 10 predictors for the MACE selected by RSF are shown in Figure 1. Expected cardiovascular (CV) risk predictors like blood pressure, Canadian CV Society angina classification (CCS), age, and a history of various CV procedures consistently emerge amongst the top ten predictors of the primary MACE outcome across all gender and age specific subgroups. Interestingly, RSF also identified renal function biomarkers like serum potassium and glomerular filtration rate as common top ten predictors. Conclusion: Using ML, we uncovered in an unbiased fashion, gender and age groups specific unanticipated top predictors for MACE in PEACE trial. This underscores the value of gender and age specific predictors to examine the efficacy and outcomes of therapeutic interventions in advancing precision and personalized medicine.

Introduction: NHLBI supported Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes trial (BARI2D) (NCT00006305) evaluated patients with type 2 diabetes and coronary artery disease. Primary trial analysis found no significant differences in rates of all-cause mortality (ACM) among patients who underwent 1) prompt revascularization with medical therapy versus aggressive medical therapy alone and 2) insulin-sensitization medical strategies versus insulin-provision. We reused publicly available individual patient-level data from NHLBI Data Repository (BioLINCC) to perform hypothesis-generating secondary analysis by machine learning (ML), using random survival forest (RSF) to identify gender, race, and age specific baseline predictors for ACM. Methods: The total 2368 trial participants was separated into several subgroups based on gender (female and male), age (40-49, 50-59, 60-69, 70-80), and race (Non-Hispanic White, Hispanic White, Non-Hispanic Non-White, and Hispanic Non-White). RSF was performed on 84 baseline variables to identify predictors of the primary outcome, ACM. The top 10 predictors for each subgroup were tested in a Cox proportional hazards model Results: Top 10 predictors of ACM are shown in Table 1. Although anticipated cardiovascular (CV) and diabetic predictors appeared among the top predictors, at the same time, renal function biomarkers like serum creatinine, urine albumin/creatinine ratio, and serum potassium uniquely showed among the top 5 predictors across the gender, age, and race specific subgroups. Conclusions: Using ML, we uncovered in an unbiased fashion, gender, race and age groups specific unanticipated top baseline predictors of ACM in BARI2D trial. This highlights the value of gender, race and age groups specific predictors of outcomes for determining the efficacy of therapeutic interventions and help advance precision medicine.

Introduction: NHLBI supported STICHES trial (The Surgical Treatment for Ischemic Heart Failure Extended Study) (NCT00023595) was conducted to test whether blood flow restoration by coronary revascularization recovers chronic left ventricular dysfunction and improves survival, as compared to medical therapy alone in patients with congestive heart failure and coronary artery disease amenable to surgical revascularization. We reused publicly available individual patient-level STICHES trial data from NHLBI Data Repository (BioLINCC) to perform hypothesis-generating secondary analyses by machine learning (ML) using random survival forest (RSF) to identify gender, race and ethnicity, and age specific predictors for all-cause mortality (ACM). Methods: The population was sub-grouped by gender (male vs. female), race (white vs. Hispanic/Latinos/non-white), and age (< 55, 55-60, 61-69, and ≥70). RSF was performed on 48 baseline variables from 1212 patients to identify predictors of ACM. Top 10 RSF predictors for each subgroup were included in a multivariate analysis using a Cox proportional hazards model. Results: Top 10 predictors of ACM are shown in Table 1. While known cardiometabolic and vascular predictors were among the top predictors, RSF uniquely identified renal function related biomarkers and plasma sodium among important top predictors across the subgroups. Age was an important predictor for male and female, Hispanics/Latinos/non-whites, and patient groups ≥70 years old. Also, top predictors of ACM were current smoking status among age groups of Conclusions: Using ML, we uncovered in an unbiased fashion, gender, age, race and ethnicity specific, unanticipated top predictors of ACM in STICHES trial. This highlights the value of ML for analyzing disease and therapeutic intervention outcomes to help implement precision medicine.

Background The coronavirus disease 2019 pandemic is expected to affect operations and lifestyles of interventional cardiologists around the world in unprecedented ways. Timely gathering of information on this topic can provide valuable insight and improve the handling of the ongoing and future pandemic outbreaks. Methods and Results A survey instrument developed by the authors was disseminated via e‐mail, text messaging, WhatsApp, and social media to interventional cardiologists between April 6, 2020, and April 11, 2020. A total of 509 responses were collected from 18 countries, mainly from the United States (51%) and Italy (36%). Operators reported significant decline in coronary, structural heart, and endovascular procedure volumes. Personal protective equipment was available to 95% of respondents; however FIT‐tested N95 or equivalent masks were available to only 70%, and 74% indicated absence of coronavirus disease 2019 pretesting. Most (83%) operators expressed concern when asked to perform cardiac catheterization on a suspected or confirmed coronavirus disease 2019 patient, primarily because of fear of viral transmission (88%). Although the survey demonstrated significant compliance with social distancing, high use of telemedicine (69%), and online education platforms (80%), there was concern over impending financial loss. Conclusions Our survey indicates significant reduction in invasive procedure volumes and concern for viral transmission. There is near universal adoption of personal protective equipment; however, coronavirus disease 2019 pretesting and access to FIT‐tested N95 masks is suboptimal. Although there is concern over impending financial loss, substantial engagement in telemedicine and online education is reported.

Chronic kidney disease (CKD) is an established predictor of more advanced peripheral artery disease (PAD) and vascular calcification. However, clinical outcome data for these patients remains inadequately defined. Using the ongoing multicenter Excellence in Peripheral Artery Disease (XLPAD)

PAD is a spectrum of disease ranging from intermittent claudication (IC) to critical limb ischemia (CLI). Recent data suggest that the underlying pathophysiology of these two diseases may differ. We sought to characterize patient and lesion level differences between IC and CLI patients undergoing

Background: Patients with type 2 diabetes (T2D) are at high risk of cardiovascular (CV) morbidity/mortality. The ACCORD trial (NCT00000620) tested intensive glycemic, lipid and blood pressure interventions on major CV events in 10,251 T2D patients with baseline HbA1c concentration >7.5%. Despite its landmark findings, a data-driven systematic evaluation of predictors for major cardiovascular events among hundreds of ACCORD variables has not been conducted. Methods: Random Survival Forest (RSF), a machine-learning method for survival analysis, identified important predictors for total mortality (TM), CV death (CVd), hospitalization/death due to heart failure (hdHF), fatal/non-fatal stroke (CVA), non-fatal myocardial infarction (MI) and MACE (composite of CVd, MI and CVA). Among 378 risk factors, including some highly correlated features, the top-ranked predictors (collected at baseline or derived from repeated measures prior to events) were selected, resulting in a hierarchy of predictive variables. Effects of RSF-selected predictors were then evaluated by multivariate Cox Proportional Hazards Models. Results: Table 1 presented the top ten predictors for six major events. Variables associated with changes in renal function predicted TM, CVd, and hdHF with ~90% accuracy. Insulin use was an important predictor along with predefined composite renal microvascular events for MI, CVA and MACE (74-79% accuracy). The Cox regression models based on RSF variable selection yielded similar findings for these important predictors of events. Conclusions: RSF approach revealed that insulin use and overt renal microvascular events were predictors for the occurrence of MI, stroke, and MACE in T2D patients. Moreover, dynamic changes in urinary renal function biomarkers had additional predictive values for fatal events. These results provide important clinical insights for reducing CV events in Type 2 diabetes patients.

Introduction: An objective of the Meta-AnalyTical Interagency Group (MATIG) is to conduct patient-level meta-analyses of cardiovascular outcomes using data from publicly available repositories. We describe challenges with data re-use from a seminal trial, provide a systematic approach to identify and curate data elements for hypothesis generation, and establish stackable trials to support these analyses. Methods: We used data from the ACCORD trial to assess risk factors and their gender specific differences for the event of hospitalization or death due to heart failure (hdHF), in patients with type 2 diabetes*. We identified the data elements needed to answer the research questions, reviewed the trial protocol to verify definitions, extracted patient-level data, performed quality assessment and statistical analysis. The results showed a gender difference in the effect of intensive vs. standard glucose-lowering therapy on hdHF. To validate the findings, we sought additional trials in BioLINCC to develop a compendium for meta-analysis, and repeated these steps for each trial. Results: Challenges for reusing the ACCORD trial included access to complete patient-level data and metadata. The compendium, developed to evaluate the stackability** of data across trials, identified differences in trial designs, patient populations, study interventions, and data elements that may impact the feasibility and interpretation of meta-analysis. An example of compendium components is shown in Table 1. Conclusion: High-quality metadata facilitate re-use of trial repository data. This compendium standardizes common data elements for gender, racial and age-group specific outcome assessment in major clinical trials. It provides the framework to assess the fitness of trials for patient-level meta-analyses. Efforts are underway by MATIG to expand the compendium to include risk factors and major cardiovascular outcomes across multiple large trials for meta-analysis.

Background The AVERTTM Contrast Modulation System (AVERT) (Osprey Medical, MN) is designed to reduce contrast volume administration during angiography. The AVERT provides an adjustable resistance circuit which decreases the pressure head delivering contrast towards the patient. The AVERT has not been previously studied in patients undergoing peripheral digital subtraction angiography (DSA). The purpose of this study was (1) to evaluate contrast savings with the AVERT and (2) to evaluate the ability to generate clinically acceptable DSA images in the process. To better define the mechanism of action in the peripheral circulation, we also developed a bench model to study the effects of the AVERT on the hydrodynamics of contrast delivery. Methods Patients undergoing lower extremity DSA (diagnostic or intervention, sheath or catheter) were studied. The following variables were recorded for each injection: starting control syringe contrast volume, contrast volume injected towards patient, contrast volume returned to AVERT reservoir, net contrast administered to the patient and % savings. The AVERT resistance was adjusted manually based on operator's discretion—balancing image quality and contrast savings. Results About 408 DSA angiographic sequences were obtained in 22 patients undergoing 29 procedures. Almost 68% of the patients had chronic kidney disease. An 82% presented with critical limb ischemia, 18% had claudication. There was an overall 37% ± 14% savings of contrast (31% for diagnostic DSA, 40% for interventional procedures). Overall 91% of all images were acceptable for clinical decision making. Specifically, 94% of diagnostic and 87% of interventional images were acceptable. Injection through a 4 Fr catheter (77% acceptable) resulted in poorer image quality as compared to a 5 Fr catheter (96% acceptable). Image quality for 5, 6, and 7 Fr sheath injections was 86%, 91%, 98%, respectively. The bench model of peripheral angiography demonstrated a significant reduction in reflux of contrast proximal to the end of the catheter without loss of antegrade image quality – confirming the in vivo findings. Conclusions We demonstrate that the use of the AVERT device during peripheral angiography results in significant contrast savings without compromising image quality. © 2015 Wiley Periodicals, Inc.

Target-lesion revascularization (TLR) and loss of patency remain high following treatment of in-stent restenosis (ISR) of the femoropopliteal (FP) artery. Excimer laser atherectomy (ELA) is effective in reducing TLR and improves patency at 6-month and 1-year follow-up when compared with balloon angioplasty (PTA). The long-term sustainability of these early results is unknown. We present a retrospective analysis from our center on the 5-year outcomes of ELA in the treatment of ISR of the FP arteries.Patients who underwent ELA for FP-ISR from February 2005 to April 2010 at a single medical center were included. Demographics, angiographic and procedural variables were included. Major adverse events and 5-year TLR and target-vessel revascularization were obtained from medical records. Descriptive analysis was performed on all variables. Kaplan-Meier survival curves for TLR were plotted censored for death among patients who died before the occurrence of a TLR.Forty consecutive patients (mean age, 67.2 ± 9.0 years; 57.5% males) were included. Angiographic variables included: lesion length, 210.4 ± 104.0 mm; lesion severity, 93.9 ± 8.9%; and number of vessel runoffs, 1.7 ± 1.0. All patients were treated with adjunctive PTA. Acute procedural success was achieved in 92.5% of vessels. Distal embolization requiring treatment was 2.5%. No unplanned amputation occurred. Total deaths occurred in 8/40 (20%). At 5-year follow-up, TLR occurred in 62.5% with the steepest decline in freedom from TLR occurred in the first year followed by a less decline in the subsequent 2 to 3 years.ELA for FP-ISR continues to show progressive increase in TLR up to 5-year follow-up, but mostly occurs in the first 3 years after index procedure. These data suggest that a minimum follow-up of 3 years is needed to determine stability of treatment of FP-ISR with laser.

Elevated low-density lipoprotein cholesterol (LDL-C) is associated with adverse cardiovascular outcomes. The strategy of target-based LDL-C lowering to reduce the risk of coronary heart disease and secondary event rates is now well established. However, the strategy for treating to a target LDL-C, and whether there is a lower threshold level for LDL-C continues to be debated. We present, and critically analyze the evidence for a target-based LDL-C lowering strategy, and the safety and efficacy of intensive plasma LDL-C-lowering with traditional, and novel LDL-lowering therapies below current guideline targets.

Aortocoronary dissection can complicate percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs).We retrospectively examined the frequency and outcomes of aortocoronary dissection among 336 consecutive CTO PCIs performed at our institution between 2005 and 2012 and performed a systematic review of the published literature.Aortocoronary dissection occurred in six patients (1.8%, 95% confidence intervals 0.7%, 3.8%). All aortocoronary dissections occurred in the right coronary artery (CTO target vessel in five patients and donor vessel in one patient). The baseline clinical characteristics of patients with and without aortocoronary dissection were similar. Compared to patients without, those with aortocoronary dissection were more likely to undergo crossing attempts using the retrograde approach (25% vs. 67%, P = 0.036) and experience a major complication (2.4% vs. 33.3%, P = 0.008). Technical and procedural success rates were similar in both groups. Of the six patients with aortocoronary dissection one underwent emergency coronary bypass graft surgery (CABG), four were treated with ostial stenting, and one was treated conservatively without subsequent adverse clinical outcomes. Systematic literature review provided 107 published cases of aortocoronary dissection during PCI, that occurred mainly in the right coronary artery (74.8%) and were treated with stenting (49.5%), emergency CABG (29%), or conservatively (21.5%).Aortocoronary dissection is an infrequent complication of CTO PCI and although it can be treated with stents in most patients, it may infrequently require emergency CABG.

The risk of distal embolization (DE) during infrainguinal peripheral artery interventions (PAI) is often mitigated by the use of embolic protection devices. There are limited data on the use of filters with the Jetstream (JS) atherectomy device, a rotational cutter with aspiration capacity. The Nav-6 filter is uniquely suited for use with the JS due to its wire compatibility and detachment from the filter; however, data on the off-label use of this combination have not been reported.Consecutive patients between October 2008 and April 2015 undergoing endovascular infrainguinal PAI with JS were analyzed as part of the Excellence in Peripheral Artery Disease (XL-PAD) registry (NCT01904851). Patients were divided into two subgroups with Nav-6 filter use vs no filter use. Descriptive and univariate analyses were performed.Among 141 patients (mean age, 67.8 ± 10.8 years; 169 lesions) included in this study, the Nav-6 filter was used in 82 (59%). Use of a filter was more frequent in longer lesions (146 ± 106 mm vs 91 ± 72 mm; P=.01), in more severe stenoses (95% vs 87%; P=.04), and in chronic total occlusions (33% vs 8.3%; P=.01). Patients receiving filters had longer procedure duration (102 ± 51 min vs 66 ± 41 min; P=.01) and longer fluoroscopy times (31 ± 16 min vs 21 ± 10 min; P.001). Use of the Nav-6 filter with the JS during PAI was associated with numerically lower rates of DE (1.8% vs 8%; P=.10) and similar rates of death and amputation. At 12 months, the target-lesion revascularization rate was higher in the filter group (22% vs 2.7%; P=.02), likely secondary to use of the filter in more complex lesions.Nav-6 filter during JS atherectomy was predominantly used during complex infrainguinal PAI and was associated with less occurrence of DE.

Coronary artery disease is the leading cause of death in Type 2 diabetes patients (T2D) with lipid abnormalities. Fibrates have emerged as second-line agents to reduce circulating triglycerides and elevate HDL-C. The ACCORD Lipid study, a subset of the ACCORD trial([NCT00000620][1]), investigated

Distal embolization during endovascular infrainguinal interventions is frequently encountered and requires additional therapy in 2-3% of cases. There are no uniform recommendations to the use of embolic protection devices (EPD) when treating the lower extremity arteries. It is unclear whether a

Relaxin-3 (RLX3), a newly identified member of the relaxin peptide family, is distinguished by its enriched expression in GABA projection neurons of the pontine nucleus incertus (NI), which are postulated to participate in forebrain neural circuits involved in behavioural activation and stress responses. In this regard, corticotrophin-releasing factor-1 receptor (CRF(1)) is abundantly expressed by NI neurons; central CRF administration activates c-fos expression in NI; and various stressors have been reported to increase NI neuron activity. In studies to determine whether a specific neurogenic stressor would activate RLX3 expression, we assessed the effect of a repeated forced swim (RFS) on levels of RLX3 mRNA and heteronuclear (hn) RNA in rat NI by in situ hybridization histochemistry of exon- and intron-directed oligonucleotide probes, respectively. Exposure of rats to an RFS (10 min at 23 degrees C, 24 h apart), markedly increased RLX3 mRNA levels in NI at 30-60 min after the second swim, before a gradual return to basal levels over 2-4 h, while RLX3 hnRNA levels were significantly up-regulated at 60-120 min post-RFS, following a transient decrease at 30 min. Systemic treatment of rats with a CRF(1) antagonist, antalarmin (20 mg/kg, i.p.) 30 min prior to the second swim, blunted the stress-induced effects on RLX3 transcripts. Relative levels of RLX3-immunostaining in NI neurons appeared elevated at 3 h post-swim, but not at earlier time points (30-60 min). These results suggest that acute stress-induced CRF secretion can rapidly alter RLX3 gene transcription by activation of CRF(1) present on NI neurons. More generally, these studies support a role for RLX3 neural networks in the normal neural and physiological response to neurogenic stressors in the rat.

Background: Metformin is associated with improved skeletal muscle glucose uptake and improves skeletal muscle energetics. There is limited data of the impact of metformin us on need for repeat revascularization in patients with symptomatic peripheral artery disease (PAD) treated with endovascular revascularization. Methods: We compared need for vessel revascularization (TLR) rates in patients with diabetes mellitus (DM) treated with metformin and without, to non-DM enrolled in the Excellence in Peripheral Artery Disease (XLPAD) registry (NCT01904851) between 2006 and 2015. Results: In the study cohort of 2140 interventional procedures, 57.4% were performed in DM (n=268 on metformin and n=961 not on metformin). Frequency of hypertension, hyperlipidemia and chronic kidney disease was higher in DM not on metformin compared to DM on metformin (p Conclusions: Metformin therapy in symptomatic PAD patients with DM following endovascular revascularization is associated with improved survival and lower need for repeat revascularization compared to diabetics not treated with metformin.

The risk of distal embolization (DE) during infrainguinal peripheral artery interventions (PAI) is often mitigated with the use of embolic protection devices. There is limited data on the use of filters with the Jetstream (JS) atherectomy device, a rotational cutter with aspiration capacity. The Nav

Purpose of review Although antiplatelet agents are frequently prescribed to patients with lower extremity peripheral artery disease (PAD), there is an overall lack of consensus among published evidence and guidelines with respect to this practice. Recent findings Antiplatelet agents are prescribed to patients with PAD to reduce both cardiovascular and limb-based events during the follow-up period. A large evidence base supports the use of antiplatelet monotherapy with aspirin or clopidogrel in patients with symptomatic PAD or a history of peripheral artery revascularization. However, antiplatelet monotherapy has not proven beneficial in patients with asymptomatic PAD. Dual antiplatelet therapy has not demonstrated a clear benefit in reducing the risk of cardiovascular events in patients with symptomatic PAD. Its role in reducing the risk of adverse limb events following endovascular or surgical revascularization also remains unclear. Recently, the use of vorapaxar in addition to aspirin and/or clopidogrel has been associated with a significant reduction in the need for repeat revascularization procedures and hospitalization for limb ischemia in patients with established PAD. Summary Eligible patients with symptomatic PAD or with a history of peripheral artery revascularization should be prescribed antiplatelet monotherapy for secondary prevention of both cardiovascular and limb events, using aspirin, clopidogrel, and/or vorapaxar. Given the significant overlap of PAD and coronary artery disease, the evidence presented in this article may have important implications for management of patients with coronary artery disease.

The AVERT(TM) Contrast Modulation System (AVERT) (Osprey Medical, MN) is designed to reduce contrast volume administration during angiography. The AVERT provides an adjustable resistance circuit which decreases the pressure head delivering contrast towards the patient. The AVERT has not been previously studied in patients undergoing peripheral digital subtraction angiography (DSA). The purpose of this study was (1) to evaluate contrast savings with the AVERT and (2) to evaluate the ability to generate clinically acceptable DSA images in the process. To better define the mechanism of action in the peripheral circulation, we also developed a bench model to study the effects of the AVERT on the hydrodynamics of contrast delivery.Patients undergoing lower extremity DSA (diagnostic or intervention, sheath or catheter) were studied. The following variables were recorded for each injection: starting control syringe contrast volume, contrast volume injected towards patient, contrast volume returned to AVERT reservoir, net contrast administered to the patient and % savings. The AVERT resistance was adjusted manually based on operator's discretion--balancing image quality and contrast savings.About 408 DSA angiographic sequences were obtained in 22 patients undergoing 29 procedures. Almost 68% of the patients had chronic kidney disease. An 82% presented with critical limb ischemia, 18% had claudication. There was an overall 37% ± 14% savings of contrast (31% for diagnostic DSA, 40% for interventional procedures). Overall 91% of all images were acceptable for clinical decision making. Specifically, 94% of diagnostic and 87% of interventional images were acceptable. Injection through a 4 Fr catheter (77% acceptable) resulted in poorer image quality as compared to a 5 Fr catheter (96% acceptable). Image quality for 5, 6, and 7 Fr sheath injections was 86%, 91%, 98%, respectively. The bench model of peripheral angiography demonstrated a significant reduction in reflux of contrast proximal to the end of the catheter without loss of antegrade image quality - confirming the in vivo findings.We demonstrate that the use of the AVERT device during peripheral angiography results in significant contrast savings without compromising image quality.

The longitudinal and the transverse beam shifts, namely, the Goos-H\"anchen (GH) and the Spin-Hall (SH) shifts are usually observed at planar interfaces. It has recently been shown that the transverse SH shift may also arise due to scattering of plane waves. Here, we show that analogous in-plane (longitudinal) shift also exist in scattering of plane waves from micro/nano systems. We study both the GH and the SH shifts in plasmonic metal nanoparticles/ nanostructures and dielectric micro-particles employing a unified framework that utilizes the transverse components of the Poynting vector of the scattered wave. The results demonstrate that interference of neighboring resonance modes in plasmonic nanostructures (e.g., electric dipolar and quadrupolar modes in metal spheres) leads to giant enhancement of GH shift in scattering from such systems. We also unravel interesting correlations between these shifts with the polarimetry parameters, diattenuation and retardance., Comment: 4 pages, 3 figures

To identify clinical, angiographic, and procedural factors associated with increased risk of periprocedural complications during chronic total occlusion (CTO) percutaneous coronary intervention (PCI).Successful CTO PCI can provide significant clinical benefit; however, procedural risks have received limited study. We sought to identify factors associated with increased CTO PCI periprocedural risk that could be utilized to guide patient and lesion selection.The clinical, angiographic, and procedural records of 336 consecutive CTO PCI procedures performed at a single center from May 2005 through 2012 were reviewed, and data on periprocedural complications were recorded. Logistic regression was performed to identify independent predictors of periprocedural complications during CTO PCI.The incidence of major and minor complications was 3.9% and 10.4%, respectively. Minor bleeding and vascular events were the most common complications (4.8%), followed by perforation (2.4%), contrast-induced nephropathy (1.8%), and transient hypotension (0.6%). Major complications were uncommon: death (0.3%); emergency coronary artery bypass grafting (0.6%); stroke (0.3%); tamponade (0.3%); clinical myocardial infarction (0.9%); donor vessel injury (0.6%); and major bleeding or vascular events (0.9%). Patients who experienced any complication had higher preprocedure troponin levels and were more likely to undergo treatment using the retrograde approach. In multivariable analysis, use of the retrograde approach was independently associated with increased risk of periprocedural complications (odds ratio, 2.057; 95% confidence interval, 1.045-4.051; P=.04).Major complications of CTO PCI are infrequent, but are more common with use of the retrograde approach.

An abnormal ankle-brachial index (ABI) is associated with higher risk for future cardiovascular (CV) events; however, it is unknown whether this association is true in patients with established coronary artery disease (CAD) and associated diabetes mellitus (DM). We evaluated 679 patients with stable CAD enrolled in the Excellence in Peripheral Arterial Disease and Veterans Affairs North Texas Healthcare System peripheral arterial disease databases. ABI and 12-month major adverse CV events (MACEs, a composite of all-cause death, nonfatal myocardial infarction, need for repeat coronary revascularization, and ischemic stroke) were assessed. Cox proportional hazard models were used to assess the association of ABI and DM with subsequent CV events. An abnormal ABI (0.9 or1.4) was present in 72% of patients with stable CAD and 68% had DM. Using patients without DM and normal ABI as reference, the adjusted hazard ratio for 12-month MACE was 1.7 (95% confidence interval [CI] 0.71 to 4.06) for patients with DM and normal ABI; 2.03 (95% CI 0.83 to 4.9) for patients without DM with abnormal ABI; and 4.85 (95% CI 2.22 to 10.61) for patients with DM and abnormal ABI. In conclusion, in patients with stable CAD, an abnormal ABI confers an incremental risk of MACE in addition to DM and traditional CV risk factors.

Relaxin-3 (RLN3) and its native receptor, relaxin family peptide 3 receptor (RXFP3), constitute a newly identified neuropeptide system enriched in mammalian brain. The distribution of RLN3/RXFP3 networks in rat brain and recent experimental studies suggest a role for this system in modulation of arousal, stress, metabolism, and cognition. In order to facilitate exploration of the biology of RLN3/RXFP3 in complementary murine models, this study mapped the neuroanatomical distribution of the RLN3/RXFP3 system in mouse brain. Adult, male wildtype and RLN3 knock-out (KO)/LacZ knock-in (KI) mice were used to map the central distribution of RLN3 gene expression and RLN3-like immunoreactivity (-LI). The distribution of RXFP3 mRNA and protein was determined using [35S]-oligonucleotide probes and a radiolabeled RXFP3-selective agonist ([125I]-R3/I5), respectively. High densities of neurons expressing RLN3 mRNA, RLN3-associated β-galactosidase activity and RLN3-LI were detected in the nucleus incertus (or nucleus O), while smaller populations of positive neurons were observed in the pontine raphe, the periaqueductal gray and a region adjacent to the lateral substantia nigra. RLN3-LI was observed in nerve fibers/terminals in nucleus incertus and broadly throughout the pons, midbrain, hypothalamus, thalamus, septum, hippocampus, and neocortex, but was absent in RLN3 KO/LacZ KI mice. This RLN3 neural network overlapped the regional distribution of RXFP3 mRNA and [125I]-R3/I5 binding sites in wildtype and RLN3 KO/LacZ KI mice. These findings provide further evidence for the conserved nature of RLN3/RXFP3 systems in mammalian brain and the ability of RLN3/RXFP3 signaling to modulate “behavioral state” and an array of circuits involved in arousal, stress responses, affective state, and cognition. J. Comp. Neurol. 518:4016–4045, 2010. © 2010 Wiley-Liss, Inc.

Successful crossing of superficial femoral artery (SFA) and below the knee (BTK) chronic total occlusions (CTO) often involves careful selection of a primary crossing strategy. We compared CTO crossing success rates with a primary wire-catheter or crossing device use. We analyzed a total of 439 SFA

Given lower durability of endovascular superficial femoral artery (SFA) revascularization in diabetics (DM) with claudication, we performed a comparative assessment of their angiographic disease in the SFA. We conducted a blinded angiographic analysis of SFA disease in 112 consecutive patients (76