Abstract
In honor of Dr Jay D. Coffman (1928–2006), distinguished internist and researcher of vascular medicine and clinical cardiology, SVM sponsors an annual award in vascular medicine and biology research. The top finalists make oral presentations during the Jay D. Coffman Young Investigator session that will be held on Thursday, June 14 at 3:00 pm. The winners of the Jay D. Coffman Young Investigator Award will be announced during the Awards Ceremony on Friday, June 15 at 9:00 am.
Top-scoring original research abstracts were invited to participate in the Best of SVM Science Rapid Fire session. Authors will give oral presentations during the Rapid Fire Session on Friday, June 15, at 10:00 am.
Authors will give poster presentations on Thursday, June 14 at 4:40 pm. Poster professors will participate and moderate the discussion.
For more information about the meeting visit: http://www.vascularmed.org/AM18.
Jay D. Coffman Young Investigator Award Presentations
YIA 1
Temporal trends in the management and clinical outcomes of acute limb ischemia within a national veteran population
1University of Colorado Division of Cardiology, Denver, CO, USA, 2VA Medical Center, Denver, CO, USA
Background: Acute limb ischemia (ALI) is associated with significant morbidity and mortality. The temporal trends in management and longitudinal outcomes of ALI remain understudied in larger cohorts.
Objective: To establish temporal trends in the incidence, management and outcomes of ALI within the largest integrated healthcare system in the United States, the Veterans Affairs Healthcare System.
Methods: We identified patients admitted to VAHS between 2003 and 2014 with a primary diagnosis of ALI. Medical and procedural management were ascertained from pharmaceutical and administrative data. Subsequent rates of major adverse limb events (MALE), major adverse cardiovascular events (MACE), and mortality were calculated using Cox proportional hazards models.
Results: From 2003 to 2014, there were 8,474 patients hospitalized for ALI across 140 facilities. Age-adjusted incidence of ALI decreased from 7.98 per 100,000 patients (95% CI: 7.28–8.75) in 2003 to 3.54 (95% CI: 3.14–3.99) in 2014. On average, the likelihood of receiving anti-platelet or anti-thrombotic therapy increased 1.3% (95% CI: 0.5 – 2.0%) per year during this time period and the likelihood of undergoing endovascular revascularization increased 4.0% (95% CI: 2.7–5.4%) per year. Clinical outcomes remained constant over time, with similar rates of MALE, MACE and mortality at one year after adjustment. See Y1A Figure.
Conclusions: Incidence of ALI is decreasing in the largest integrated healthcare system in the country, with increasing utilization of anti-thrombotic therapies and endovascular revascularization. Despite this evolution in management, patients with ALI continue to experience high rates of amputation and death within a year of the index event.
YIA 2
Clinical and genetic determinants of varicose veins: a prospective, community-based prospective study of ~500,000 individuals
1Stanford University, Stanford, CA, USA, 2Uppsala University, Uppsala, Sweden
Background: Varicose veins (VV) are a common and disabling problem and while believed that VV pathogenesis is multifactorial, there is limited understanding of the genetic and environmental factors that contribute to its formation. Large-scale studies of risk factors for VV may highlight important aspects of pathophysiology and identify groups at increased risk for disease.
Methods: We applied supervised machine learning (ML) in an agnostic search for risk factors of VV in the UK Biobank including 493,519,827 individuals free of VV at baseline. Predictors were studied using univariable and multivariable Cox regression analysis. A genome-wide association study (GWAS) was performed among 337,536 unrelated individuals (9577 cases) followed by eQTL and pathway analyses. Because height emerged as a new candidate predictor, we used LD score regression to estimate the genetic correlation between height and varicose veins. We performed Mendelian randomization (MR) analyses to assess for a causal role for height in VV.
Results: ML confirmed known (age, sex, obesity, pregnancy, history of DVT) and identified several new risk factors for VV. The most important novel predictors were leg bioimpedance and height, which both remained independently associated with VV after adjusting for traditional risk factors in Cox regression. GWAS identified 30 new genome-wide significant loci, identifying pathways involved in vascular development and skeletal/limb biology. MR analysis provided evidence that height is causally related to varicose veins.
Conclusions: Using UK Biobank data, we identified clinical and genetic risk factors which provide pathophysiological insights and will help with the future prediction of varicose vein disease.
YIA 3
CD70 modulates the role of eNOS in endothelial cells
Vanderbilt University, Nashville, TN, USA
CD70 has traditionally been identified on antigen presenting cells, interacting with CD27 on T cells. We have recently shown that CD70 is important in the formation of effector memory T cells in hypertension. However, the precise cell types that express CD70 and the role of CD70 on non-immune cells has not been investigated. Here we describe a new role of CD70 in endothelial function. CD70-/- mice demonstrated marked impairment in acetylcholine (Ach)-induced vasorelaxation compared to wild type (WT) mice (45% ± 5% versus 25% ± 4%) at baseline. There were no differences in relaxation responses to sodium nitroprusside. Pre-incubating vessels with the endothelial nitric oxide synthase (eNOS) inhibitor L-NAME blocked Ach-induced vasodilation in WT mice by nearly 75%; in contrast, L-NAME had no effect on relaxation in CD70-/- mice. This suggests that vessels of CD70-/- mice lack functional eNOS. Western blot for eNOS in aortas of CD70-/- mice showed a marked reduction of this enzyme as compared to wild type mice. We found that CD70 and eNOS interact by co-immunoprecipitation in WT mice, however this association is abolished by siRNA against CD70. Aortas from CD70-/- did demonstrate expression of both neuronal NOS (nNOS) and inducible NOS (iNOS). In order to assess functional effects of this expression, nNOS NO production was blocked with vinyl-LNIO, resulting in further impairment in vasodilation of CD70-/- mesenteric vessels; however blockade of iNOS with 1400W resulted in apparent recovery of Ach-induced vasodilation. Pre-incubating CD70-/- mesenteric vessels with L-arginine and sepiapterin also led to functional recovery in Ach-induced vasorelaxation. These data indicate that loss of CD70-/- leads to destabilization of the eNOS protein in endothelial cells. In the absence of eNOS, iNOS is expressed and appears to contribute to endothelial dysfunction, while nNOS has a compensatory role. These studies have identified a new role for CD70 in modulating endothelial eNOS protein levels and vascular function.
YIA 4
Durability of supervised treadmill exercise benefits in people with peripheral artery disease
1University of Illinois at Chicago College of Medicine, Chicago, IL, USA, 2University of North Carolina School of Medicine, Chapel Hill, NC, USA, 3University of Maryland School of Medicine, Baltimore, MD, USA, 4University of Florida College of Medicine, Gainesville, FL, USA, 5Northwestern University Feinberg School of Medicine, Chicago, IL, USA, 6Stanford University, Stanford, CA, USA, 7National Institutes of Health, Bethesda, MD, USA, 8University of Chicago, Chicago, IL, USA, 9University of California San Diego School of Medicine, La Jolla, CA, USA
Background: CMS now provides coverage for 12 weeks of supervised exercise therapy (SET) for peripheral artery disease (PAD). However, little is known about the durability of SET benefits, after therapy completion. The Study to Improve Leg Circulation (SILC) trial studied the durability of SET benefits for people with PAD.
Methods: PAD participants were randomized to one of three groups for six months: SET, supervised resistance training (SRT), or attention control. After 6-month follow-up testing, participants were contacted by telephone at regularly scheduled intervals for an additional 6 months. They were encouraged to maintain the program on their own but were not participating in supervised exercise. The primary outcome was change in 6-minute walk (6MW) at 6-month follow up and results were reported previously. This report focuses on the exploratory outcome of change in 6MW at 12-month follow-up.
Results: A total of 156 PAD participants were randomized (mean age 70.9 ± 10.3 years, mean ABI 0.60 ± 0.16, 44% male, 40% black). Of these, 84% completed 12-month follow-up. At 6-month follow up, 6MW distance was improved in the SET group but not the SRT group, compared to the control. Between 6 and 12-month follow up, 6MW declined significantly in the SET but not the SRT group, compared to control. There was no difference between change in 6MW distance between baseline and 12-month follow up in either SET or SRT groups compared to control (see YIA4 Table).
Conclusions: In the SILC randomized trial, a SET intervention that significantly improved the 6MW distance at 6-month follow-up did not have durable benefits. These results do not support a persistent beneficial effect of SET on walking distance in patients with PAD.
Effect of 6 months of supervised exercise on change in 6-minute walking distance (in meters) at 12-month follow-up in patients with peripheral artery disease.
YIA 5
Efficacy and safety of vorapaxar on cardiovascular and limb outcomes in a broad population of patients with peripheral artery disease: analysis from TRA2P-TIMI 50
Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Background: Patients with peripheral artery disease (PAD) are at an increased risk of atherothrombotic events. Randomized trials of therapies in PAD use differing definitions inclusion criteria. Vorapaxar reduces ischemic risk in patients with symptomatic PAD without qualifying CAD or stroke. The balance of efficacy and safety in a broader PAD population including those with prior MI is relevant to clinical practice.
Methods: The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50 (TRA2P-TIMI) trial randomized 26,449 patients with prior MI, ischemic stroke, or PAD to vorapaxar or placebo and followed for 2.5 yrs (med). Randomization was hierarchical so patients were only classified as qualifying PAD if they had no qualifying CAD or stroke. In this post hoc analysis, we examined the effect of vorapaxar in all of the 6146 pts with PAD regardless of CAD history.
Results: In patients with any PAD, vorapaxar reduced the composite endpoint of CV death, MI or stroke as compared with placebo (10.7% vs. 12.5%; HR 0.85, 95% CI 0.73-0.99; P=0.034). Additionally, vorapaxar also reduced the composite endpoint of hospitalization for acute limb ischemia, urgent peripheral revascularization and major amputation for limb ischemia (3.2% vs. 4.7%; HR 0.70, 95% CI 0.53-0.92; P=0.011). Overall, vorapaxar lowered the composite outcome of major adverse CV events (MACE) or major adverse limb events (MALE) as compared with placebo (13.3 vs. 16.4%; HR, 0.81, 95% CI, 0.71-0.93; P=0.003) (See YIA5 Figure). Treatment with vorapaxar was associated with an increased risk of major bleeding as defined per the ISTH criteria (7.8% vs. 5.8%; HR 1.39, 95% CI, 1.12-1.71; P=0.003) but no excess in fatal bleeding or intracranial hemorrhage.
Conclusions: Among patients with PAD, vorapaxar, on a background of aspirin and/or clopidogrel significantly reduces both major adverse CV events and major adverse limb events.
Best of SVM Science Rapid Fire Session
Rapid Fire 1
Concentrated Growth Factors (CGF) for the treatment of vascular non-healing ulcers: Preliminary data of a randomized multicenter prospective study
1Hermitage Hospital, Naples, Italy; 2Massachusetts General Hospital, Boston, MA, USA; 3Villa del Sole Hospital, Caserta, Italy; 4University of Naples Federico II, Italy
Background: Non-healing ulcers present a therapeutic challenge. Concentrated Growth Factors (CGF) is an autologous preparation obtained from the patient’s own blood. It is rich in platelet-derived growth factors (PDGF, TGF- beta1, TGF-beta2, FGF, VEGF, IGF) and CD34+ stem cells (figure). These factors have a role in stimulation of cell proliferation, remodeling of the extracellular matrix, vascular maintenance, neovascularization and angiogenesis. Topical application of CGF is a new technique to treat non-healing ulcers.
Methods: In this randomized study, we compared CGF dressing (topical application of CGF weekly, for 6 weeks) with standard dressing (application of polyurethane film or foam weekly, for 6 weeks) in patients with non-healing ulcers. Ulcer size was calculated using MOWA graphics software (MObile Wound Analyzer). The primary end-point was the reduction of at least 50% of surface and volume of lesions after 6 weeks of treatment.
Results: A total of 61 patients were randomized (mean age 69.3 years, 50.8% male). The primary end-point occurred in 19 of 31 patients (61.3%) in the CGF group, as compared with 2 of 30 (6.7%) in the standard dressing group (p <0.001). In the CGF group, the primary end-point occurred in 9 of 12 patients (75%) with venous ulcers, 6 of 9 patients (66.6%) with arterial diabetic ulcers, 2 of 3 (66.6%) patients with neuropathic ulcers and 2 of 3 (66.6%) patients with traumatic ulcers. Patients with vasculitic ulcers (n=4) did not benefit from the CGF therapy. No patient presented with side effects during follow-up. See RF1 Figure.
Conclusions: The CGF therapy was more effective than standard dressing for the treatment of non-healing ulcers of multiple etiologies. A larger study is currently underway.
Rapid Fire 2
Real-time modulation of platelet phenotype and vein wall biology in patients with chronic venous insufficiency
University of Rochester Medical Center, Rochester, NY, USA
Background: The role of antiplatelet agents in the modulation of arterial disease is well described, but a paucity of data exists regarding their role in chronic venous insufficiency (CVI). We hypothesize that platelet responses to various antiplatelet agents are altered when comparing platelet function within refluxing and non-refluxing vein segments and may alter vein wall biology.
Methods: Isolated platelets were obtained simultaneously from the patient antecubital vein (AC) and a refluxing greater saphenous vein (GSV) during surgical phlebectomy and compared to platelets from healthy individuals. Non-refluxing GSV was harvested for coronary bypass. Platelet surface receptor activation was assessed through P2Y12 (clopidogrel), PAR1 (vorapaxar), and thromboxane (aspirin) pathways by flow cytometry. Immunoblotting assessed CD41 (platelet) and CD45 (WBC) within the wall of vein samples.
Results: Platelets from refluxing GSV showed a significant increase in reactivity via all signaling pathways when compared to platelets from the AC in the same patient. Conversely, platelets collected from the AC in CVI patients showed a significant decrease in reactivity to all agonists compared to AC in healthy individuals. GSV with CVI had a reduction in CD41 content, but a seven-fold increase in the CD45:41 ratio, compared to GSV from healthy people (see RF2 Figure).
Conclusions: Platelet activation by these clinically relevant pathways is enhanced locally in the refluxing GSV, yet systemic, circulating platelets isolated from CVI patients are three-fold less active than platelets from healthy people. Our data suggest that reflux may locally alter the circulating platelet phenotype and in turn also have a role in remodeling the vein wall.
Rapid Fire 3
The ecto-enzyme CD73 reduces venous thrombogenesis by generating adenosine and inhibiting innate immune activation
University of Michigan, Ann Arbor, MI, USA
Background: Deep vein thrombosis (DVT) is a growing public health concern. DVT is marked by innate immune activation and coagulation. Neutrophils extrude DNA to form extracellular traps (NETs), potentiating thrombosis. CD73 is an ecto-enzyme at the nexus of vascular inflammation and coagulation, phosphohydrolyzing AMP to the anti-thromboinflammatory nucleoside adenosine. We hypothesized that CD73 protects against venous thrombosis.
Methods: DVT was induced in WT and CD73-/- mice by inferior vena cava (IVC) stenosis. Thrombus frequency/size were quantified. We examined IL-1 beta and tissue factor by immunostaining, plasma cell-free DNA (cfDNA) as a marker for NETs using a Pico green assay, and degraded NETs in vivo by DNase injection.
Results: CD73-/- mice developed larger thrombi (2.5-fold), with more clot extension (2.6-fold) than WT mice (P<0.005, n=14-36). Plasma cfDNA was elevated in CD73-/- vs. WT mice 6h after surgery(P<0.05, n=10-11) with exaggerated in vitro NET formation. DNase injection in CD73-/- mice reduced thrombus frequency by 68%, and burden by 65% (P<0.05,n=8). CD73-/- clots had increased cellularity, tissue factor and IL-1 beta. Additional studies implicate adenosine 2A receptor (A2AR) as a critical effector in protection from DVT.
Conclusion: The adenosinergic ecto-enzyme, CD73 protects against venous thrombosis. CD73-/- mice have increased DVT burden and elevated cfDNA early after DVT induction, implicating NETs in CD73-/- thrombogenesis, and DNase injection rescued the exaggerated thrombotic phenotype in CD73-/- mice. CD73 and A2AR signaling are a novel link between venous inflammation and thrombosis. Experiments are underway to delineate the mechanisms underlying adenosine-mediated venous protection.
Rapid Fire 4
Tobacco product flavorings induce endothelial dysfunction
1Boston University School of Medicine, Boston, MA, USA, 2University of Louisville, Louisville, KY, USA
Alternative tobacco products are available in a vast array of flavors, which serves as a driver of use among adults and youth. The cardiovascular health effects of the flavoring additives are largely unknown. In a recent study of e-cigarette users (N=63), the majority prefer menthol (31.7%), fruit (25.4%), and confectionary flavored products (11.1%). We sought to evaluate the effects of flavoring additives within these classes on measures of endothelial cell (EC) function. Freshly isolated EC from human participants and commercially available human aortic EC (HAECs) were incubated with the flavoring additives (0.1-100 mM) for 90 minutes and measures of apoptosis, oxidative stress, inflammation, and nitric oxide (NO) were evaluated. In freshly isolated venous EC, non-menthol and menthol cigarette smokers had lower A23187-stimulated NO production compared to non-smokers. Incubation of freshly isolated EC from non-smokers with menthol or eugenol, impaired A23187-stimulated NO. Cell death and oxidative stress were induced only at high concentrations of unheated flavorings unlikely to be achieved in vivo. Lower concentrations of unheated select flavors (vanillin, eugenol, and menthol) increased IL-6 expression and impaired A23187-stimulated NO production consistent with endothelial dysfunction. To simulate e-cigarette heating, flavoring additives were vaporized at 200°C/700°C and condensed. Both heated and unheated flavoring additives had similar effects on endothelial function, suggesting that heating does not alter the flavor toxicity. Our work suggests that acute exposure of endothelial cells to flavoring additives used in tobacco products induces endothelial dysfunction that may have relevance to cardiovascular injury.
Poster Abstracts
Poster 1
ECG gated flow spoiled-fresh blood imaging non-contrast MRA towards improving its ability to detect run-off flow with clinically significant disease
Lehigh Valley Health Network-Pocono, East Stroudsburg, PA, USA
Background: Our purpose was to evaluate the sensitivity of flow spoiled-fresh blood imaging non-contrast MRA (NC-MRA) in the detection of reconstituted flow, run-off and target vessel in the setting of severe stenosis (>70%) and occlusions of moderate and large sized vessels. A new automatic ECG algorithm was implemented.
Methods: This study was approved by the Western Institutional Review Board. Nineteen (19) patients with symptomatic peripheral artery disease (PAD) who were referred for lower extremity angiography (XRA) underwent NC-MRA using a 1.5 T MRI (Vantage TitanTM, Toshiba) immediately prior to undergoing XRA. A four-station runoff was performed using Delay Tracker. Appropriate flow-spoiling gradient pulses were used to optimize the separation of arteries and veins. Source, subtracted and maximal intensity projection (MIP) data sets were reviewed to assess for reconstituted flow, run off and target vessel identification in the presence of severely stenotic lesions (>70%) and occlusions of moderate and large sized vessels.
Results: The sensitivity and PPV for the detection of severely stenotic lesions and occlusions of moderate and large sized vessels was 100%. The sensitivity in the detection of reconstituted flow for moderate sized vessels was 92.3%. The sensitivity for detection of reconstituted flow, run off and target vessel for small vessels was 44.4%, 35.3 % and 31.3%. See P1 Figure.
Conclusion: NC-MRA is a valuable diagnostic imaging modality that may be used to comprehensively demonstrate the location and severity of disease. The use of NC-MRA as a preoperative planning tool for revascularization requires further optimization in the distant peripheral arteries. Methods for optimizing the protocol are currently under investigation.
Note - figure is in color online.
Poster 2
Three months of fish oil supplementation increases specialized pro-resolving lipid mediators in patients with peripheral artery disease (The OMEGA-PAD II Trial)
1University of California, San Francisco, San Francisco, CA, USA, 2Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
Background: The OMEGA-PAD II trial is a double-blinded randomized placebo-controlled trial designed to assess the effects of 3 months of high-dose n-3 polyunsaturated fatty acid (PUFA) supplementation on inflammation and endothelial function in patients with peripheral artery disease (PAD).
Methods: Twenty-four patients with stable claudication received 4.4 g/day of fish oil or placebo for 3 months. The primary outcome was changes in C-Reactive protein (CRP) levels. Secondary outcomes included changes in plasma levels of specialized pro-resolving mediators (SPM), omega-3 index, and endothelial function as measured by brachial artery flow-mediated vasodilation (FMD).
Results: There was no significant change in CRP in the fish oil group (0.80 ± 5.47 mg/L increase from baseline, p = 0.67). The omega-3 index significantly increased from baseline (fish oil 7.2 ± 1.2%, p < 0.001; placebo -0.4 ± 0.4%, p = 0.31; between group difference p < 0.001). Levels of eicosapentaenoic acid, docosahexaenoic acid (EPA) and markers of SPM synthesis increased from baseline (see P2 Figure). We identified several SPMs (E-series and D-series resolvins, protectins, and maresins) in the plasma and observed significant increases in lipoxin A5 (fish oil 0.57 ± 0.70 pg/mL, p = 0.05; placebo 0.01 ± 0.38 pg/mL, p = 0.93; between group difference p = 0.04) and resolvin E3 (fish oil 154 ± 171 pg/mL, p = 0.04; placebo 32 ± 54 pg/mL, p = 0.08; between group difference p = 0.04). There were no significant changes in FMD.
Conclusion: N-3 PUFA supplementation increased plasma levels of resolvers of inflammation. Changes in these inflammation resolution pathways could explain the mechanism underlying previously reported protective effects of n-3 PUFAs. Larger cohorts are needed to determine whether changes in these pathways can improve clinical outcomes.
Poster 3
Peripheral vascular manifestation in patients receiving central nervous system stimulants: A Case Series
1Massachusetts General Hospital, Boston, MA, USA; 2Lahey Hospital and Medical Center, Burlington, MA, USA; 3Gagnon Heart Hospital, Morristown, NJ, USA; 4Newton-Wellesley Hospital, Harvard Medical School, Newton, MA, USA.
Amphetamine, its related derivatives and analogues (ADRA) are highly addictive central nervous system stimulants that are associated with many side effects. However, reports of peripheral arterial manifestations associated with ADRA usage are scarce. We retrospectively reviewed the records of 16 patients (median age 37 (IQR 31-47), 20% male) referred to our vascular service while prescribed ADRA (see P3 Table). Follow up was available for a median of 3 years (IQR 3-4.5). The most common presenting symptom (62.5%) was mild Raynaud’s syndrome (RS). Six patients developed severe manifestations including tissue loss and need for amputation. Most patients (75%) refused to stop the medication during follow-up. The presence of a rheumatological disease was significantly associated with the development of severe manifestations in this cohort (relative risk = 6, p = 0.001), while the presence of cardiovascular risk factors was not associated with adverse event (coefficient of interaction = 0.15, p = 0.175). In conclusion, RS and digital gangrene can be seen in patients receiving ADRA. The presence of an underlying rheumatological disease significantly increases the risk of developing adverse outcomes such as amputation in patients using ADRA. It is important to search for ADRA usage in the history of patients presenting with peripheral arterial disease and to advise them to withhold ADRA, especially if rheumatological disease co-exists.
Summary of all patients.
ADRA: Amphetamine, its related derivatives and analogues; BB: beta-blocker; CCB: calcium channel blocker; CTA: computerized tomographic angiography; CV: cardiovascular; FU: follow up; Med: vasoactive medication; MRA: magnetic resonance angiography; N/A: not available; OCD: Obsessive Compulsive Disorder; Psy: presence of major psychiatric diagnosis; PVR: pulse volume recording; SLE: Systemic Lupus Erythematosus; SS: Systemic Sclerosis; DM, diabetes mellitus; HT, hypertension; ESRF, end-stage renal failure; RS, Raynaud’s syndrome.
Poster 4
Prevalence of peripheral arterial disease (PAD) among filipino patients living with human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) in a government-run treatment hub of a tertiary hospital
University of the Philippines - Philippine General Hospital, Manila, Philippines
Background: The prevalence of HIV and AIDS is increasing in the Philippines. Epidemiologic studies observed a rising prevalence of atherosclerotic cardiovascular conditions in this population such as coronary artery disease and peripheral artery disease (PAD). Accelerated atherogenesis and endothelial dysfunction have been cited as possible pathophysiologic mechanisms. To date, the prevalence of PAD among people living with HIV and AIDS in the Philippines is unknown.
Objective: The purpose of this study was to determine the prevalence of PAD among people living with HIV and AIDS in a tertiary hospital using the National Nutrition and Health Survey (NNHeS) Claudication Questionnaire and ankle-brachial index (ABI).
Methods: This is a cross-sectional study that included 200 patients with HIV and AIDS in a tertiary hospital. Claudication was determined using NNHeS questionnaire and PAD was determined using ABI. Clinical and laboratory parameters were analyzed.
Results: PAD based on ABI was present in 15% in our young population of people living with HIV and AIDS (mean ± SD age of patients with PAD: 31 ± 7.84 years); 10.5% were asymptomatic and 4.5% were symptomatic. Higher BMI (OR 1.16, CI 1.02-1.32, p 0.03) and longer duration of HIV seropositivity (OR 1.02, CI 1.00-1.03, p 0.03) are independent risk factors for the development of PAD. Elevated LDL-C (OR 0.27, CI 0.10-0.72, p 0.01) has a negative association with development of PAD.
Conclusion: The prevalence of PAD among Filipino people living with HIV and AIDS is higher compared to the general population and can be diagnosed at an earlier age. A combination of HIV-related and traditional cardiovascular risk factors play a role in the development of PAD. Primary preventive measures such as identification and control of risk factors, lifestyle modification, and early PAD screening are likely to benefit this population.
Poster 5
Arterial stiffness and 5-year mortality in patients with peripheral artery disease
1University of Milan, L. Sacco Hospital-Milan, Milan, Italy, 2Medistat sas, Italy
An increase of arterial stiffness (arteriosclerosis) coexists in peripheral artery disease (PAD). We tested whether aortic pulse wave velocity (aPWV) and augmentation index (Aix @75HR) predict cardiovascular and all-cause mortality. In 231 patients with PAD (ankle brachial index [ABI] ≤ 0.90) and 167 patients without PAD (ABI ≥ 0.91 and < 1.3 with a normal treadmill test), the total mortality in relation to ABI, aPWV, and Aix @75HR was analyzed using Cox regression models. During a mean follow-up of 5.4 ± 2 years, a total of 47 (11.8%) deaths occurred: 39 (16.8%) in patients with PAD and 8 (4.8%) in patients without PAD. In the whole population, ABI and aPWV were associated with total mortality (HR = 0.18, 95% CI, 0.04-0.75; p = 0.018 for ABI; HR = 1.17, 95% CI, 1.06-1.28; p = 0.001 for aPWV). In the PAD group, the aPWV remained associated with an increased risk for total mortality (HR = 1.14, 95% CI, 1.03-1.26; p = 0.016) independent of cardiovascular risk factors and CAD history. In comparison to PAD survivors, PAD non-survivors showed no differences in ABI values (p = 0.324) but did have higher aPWV values (p = 0.0001). Kaplan-Meier curves showed that survival in the third tertile of aPWV was statistically lower (Log-rank test p = 0.0005) with respect to the first tertile. The results of this study suggest that in patients with PAD, aPWV may also be considered an independent indicator of total mortality.
Poster 6
Racial differences in granulocyte macrophage colony-stimulating factor (GM-CSF) effects on walking performance in peripheral artery disease: The PROPEL randomized clinical trial
1Northwestern University Feinberg School of Medicine, Chicago, IL, USA, 2University of North Carolina School of Medicine, Chapel Hill, NC, USA, 3University of California San Diego School of Medicine, La Jolla, CA, USA, 4National Institute on Aging, Baltimore, MD, USA, 5Stanford University School of Medicine, Stanford, CA, USA, 5University of Chicago Pritzker School of Medicine, Chicago, IL, USA
Background: In the PROPEL randomized trial, granulocyte macrophage colony stimulating factor (GM-CSF), when administered with and without supervised exercise (EX), did not significantly improve 6-minute walk performance in people with peripheral artery disease (PAD) compared to placebo. However, whether GM-CSF benefits specific subsets of people with PAD is unknown.
Methods: PAD participants were randomized to one of four groups and followed for six months: GM-CSF + EX, GM-CSF + attention control, placebo + EX, and placebo + attention control. Supervised exercise was administered for 6 months. GM-CSF was administered for 2 weeks. The primary outcome was change in 6-minute walk at 12 week follow-up. In exploratory analyses, differences in the effects of GM-CSF on 6-minute walk were studied according to age, sex, and African-American race.
Results: A total of 210 participants with PAD were randomized (mean age 67.0 ± 8.6, mean ABI = 0.70 ± 0.19, 39% women, 67% black). There was a significant interaction for the effects of GM-CSF on change in 6-minute walk, according to African-American race (P for interaction = 0.043 at 12-week follow-up and P for interaction = 0.0159 at 26-week follow-up). There were no significant interactions by sex or age and there were not any significant interactions for exercise. The table (P6 Table) shows changes in 6-minute walk distance, according to receipt of GM-CSF vs. placebo and whether participants were African-American or not.
Conclusions: In the PROPEL randomized trial, GM-CSF had significantly greater benefit in non-African-Americans than in African-Americans with PAD. Furthermore, the benefit in non-African-Americans was consistent with a clinically meaningful change.
Effect of GM-CSF on change in 6-minute walk in non-African-American vs. African American participants with peripheral artery disease.
Poster 7
The prevalence of coronary vasospasm using coronary reactivity testing in patients with spontaneous coronary artery dissection
1Cleveland Clinic, Cleveland, OH, USA, 2Vanderbilt University, Nashville, TN, USA
Introduction: Spontaneous coronary artery dissection (SCAD) is an important cause of myocardial infarction and sudden cardiac death, particularly in young to middle-aged women. Coronary vasospasm is another condition thought to be associated with SCAD; however, this has only been shown in isolated case reports to date.
Objective: We sought to examine the association between SCAD and coronary vasospasm by reporting the experience of vasospasm testing in patients with a history of SCAD in a large, tertiary referral center.
Methods: Single-center retrospective review of patients with history of SCAD confirmed by angiography who received provocative testing using methylergonovine in the Cleveland Clinic cardiac catheterization lab from January 1990 through December 2016. Positive vasospasm was defined as: 1) total or subtotal occlusion of at least one major coronary artery induced by administration of ergonovine and 2) resolution of said occlusion with the administration of nitrates. Patients with history of strong trauma to the chest and iatrogenic dissection (e.g. catheter-induced) were excluded from the study.
Results: We identified 11 patients who satisfied all inclusion criteria (see P7 Table). All participants were women and the mean age was 47 years. Of these, 73% received screening for fibromuscular dysplasia, and 38% of those were found to have the diagnosis. Only one of 11 patients had a positive vasospasm test in the setting of methylergonovine administration in the catheterization lab.
Conclusions: In our series, we found a low prevalence of coronary vasospasm in individuals with confirmed prior SCAD.
Baseline clinical characteristics of 11 SCAD patients with methylergonovine testing.
Includes patients who received some evaluation for FMD that included non-invasive imaging or angiogram of the renal vessels, mesenteric vessels, aorta and its branches, or extracranial arteries.
For those patients with FMD, all three had only extracranial .
SCAD, spontaneous coronary artery dissection; FMD, fibromuscular dysplasia; PCI, percutaneous coronary artery intervention; CABG, coronary artery bypass grafting.
Poster 8
Changes in calf skeletal muscle characteristics and decline in walking performance in peripheral artery disease
1Northwestern University, Feinberg School of Medicine, Chicago, IL, USA, 2National Institute on Aging, MD, USA, 3University of Maryland School of Medicine, Baltimore, MD, USA, 4University of California San Diego School of Medicine, La Jolla, CA, USA, 5University of Chicago Medicine, Chicago, IL, USA, 6University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA, 7Stanford University School of Medicine, Stanford, CA, USA
Background: People with PAD have adverse calf skeletal muscle characteristics compared to people without PAD. However, associations of adverse calf muscle changes with changes in walking performance have not been described in people with PAD.
Methods: Participants with PAD underwent computed tomography (CT) of the calf at baseline and every two years to obtain data on calf muscle area (cm2), density (grams/cm3), and percent fat. Six-minute walk distance, short physical performance battery (SPPB), 4-meter normal and fast-pace walk were measured at baseline and annually. Analyses were adjusted for age, sex, race, body mass index, smoking, ankle brachial index (ABI), comorbidities and other confounders.
Results: A total of 271 PAD participants (125 [46.13%] females, mean age = 74.37 ± 7.48 years, mean ABI = 0.64 ± 0.15) underwent baseline testing and at least one follow-up CT scan. Greater declines in calf muscle area were associated with greater declines in 6-minute walk and 4-meter normal walk pace (trend p value < 0.001 and < 0.01, respectively). The table (P8 Table) shows associations of changes in muscle measures and changes in functional performance.
Conclusion: In summary, greater adverse changes in muscle characteristics at 2-year follow-up are independently associated with a significant decline in measures of functional performance in participants with PAD. Further study is needed to determine whether interventions that prevent decline in muscle characteristics can also prevent functional decline in PAD.
Associations of percent changes in muscle measures with percent changes in functional performance in people with peripheral artery disease.
Adjusted for age, sex, race, and prior functional performance, prior muscle measures, BMI, smoking, comorbidities (including diabetes, pulmonary disease, cancer, number of (Angina, MI, CHF, stroke) and number of (knee/hip arthritis, disc disease, Spinal stenosis), ABI, and study cohort.
sSPPB, Short Physical Performance Battery; ABI, ankle brachial index.
Poster 9
Increased radial artery tonometry is associated with an increased rate of major adverse cardiac events in patients with peripheral artery disease
University of California, San Francisco, San Francisco, CA, USA
Background: Increased vascular stiffness, as measured by an increasing radial artery augmentation index (AIX), is independently associated with PAD but it has not yet been clearly demonstrated whether AIX predicts adverse cardiovascular outcomes in this population.
Methods: Seventy-two patients with PAD, defined as symptoms of claudication and an ankle-brachial index < 0.9 or history of revascularization for claudication, were recruited in 2011–2016. Radial artery applanation tonometry was performed at a baseline visit and the central AIX, normalized to 75 beats/min, and the peripheral AIX were calculated using pulse wave analysis. Incident major adverse cardiac events (MACE) were identified by subsequent chart review and defined as a composite endpoint of myocardial infarction, coronary revascularization, stroke, or death from a cardiac cause.
Results: Study subjects had comorbidities commonly associated with PAD (hypertension 93%, diabetes mellitus 39%, coronary artery disease 39%, hyperlipidemia 85%) and Rutherford categories ranged from I-III. During a median follow-up period of 34 months (IQR: 29-38), 14 patients experienced the primary endpoint. In a univariate Cox proportional hazards model, a 10-unit change in peripheral AIX was significantly associated with MACE (HR: 1.54, 95%CI 1.06-2.22, p = 0.02) but central AIX normalized to 75 beats/min was not (HR: 1.33, 95% CI 0.71-2.47, p = 0.37). In a multivariate model adjusted for CAD and age, peripheral AIX remained associated with MACE (HR: 1.56, 95% CI 1.06-2.29, p = 0.02). See P9 Table.
Conclusion: Increased vascular stiffness, as measured by the peripheral AIX, was independently associated with an increased rate of MACE. Prospective data are needed to establish whether the peripheral AIX could be a tool for risk stratification in patients with PAD.
Cox proportional hazards models for peripheral AIX predicting MACE.
All variables with a p ≤ 0.10 in bivariate analysis were included in the multivariable model.
The primary predictor was run as a univariate analysis prior to inclusion in the multivariable model.
ACE, angiotensin-converting-enzyme; AIX, augmentation index; eGFR, estimated glomerular filtration rate; HDL, high-density lipoprotein; LDL, low-density lipoprotein; HR, hazard ratio, −, not applicable; MACE, major adverse cardiac events.
Poster 10
Cardiac autonomic modulation is associated with arterial stiffness in patients with symptomatic peripheral artery disease: a cross-sectional study
1Hospital Israelita Albert Einstein, São Paulo, Brazil, 2University of São Paulo, São Paulo, Brazil
Background: Cardiac autonomic dysfunction and increased arterial stiffness play an important role in the pathophysiology of several chronic diseases, increasing mortality risk. However, whether similar associations occur in patients with peripheral artery disease (PAD) has not been previously evaluated. Thus, the aim of this study was to identify the association between cardiac autonomic modulation and arterial stiffness in patients with PAD.
Methods: In this cross-sectional study, one hundred and fourteen patients were evaluated by heart rate variability (HRV) with time (standard deviation of all RR intervals – SDNN, root mean square of the successive differences between adjacent normal RR intervals – RMSSD, and the proportion of successive RR intervals that differed by more than 50 ms – pNN50) and frequency domains. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV). Crude and adjusted linear regression analyses were performed to analyze the association between HRV and cfPWV.
Results: Non-significant crude associations were identified between cfPWV and RMSSD (P = 0.181), SDNN (P = 0.105), pNN50 (P = 0.087), low frequency normalized (LF nu, P = 0.376), high frequency normalized (HF nu, P = 0.175), and LF/HF ratio (P = 0.426). After adjustments for age, sex, smoking, body mass index, ankle-brachial index, and use of beta-blockers, significant associations were identified between cfPWV and RMSSD (P = 0.037), SDNN (P = 0.049), and pNN50 (P = 0.049).
Conclusion: Cardiac autonomic modulation was significantly associated with arterial stiffness in patients with PAD after adjustment for confounding factors. This relationship may contribute to enhanced cardiovascular risk in PAD patients and provides a target for strategies to improve patient clinical outcomes.
Poster 11
Incentivizing physical activity through activity monitoring interventions in PAD - a pilot study
1Stanford University, Stanford, CA, USA, 2University of Pennsylvania, Philadelphia, PA, USA, 3University of Chicago, Chicago, IL, USA, 4Rowan University, Glassboro, NJ, USA
*Deceased
Introduction: There is ample evidence that supervised exercise (SE) programming is efficacious to improve claudication symptoms in patients with peripheral artery disease (PAD). There is also evidence that SE is more cost effective and potentially more efficacious than revascularization procedures in this population. A significant barrier for participation in SE programs was lack of insurance coverage for this therapy, but in 2017, the Centers for Medicare and Medicaid Services approved coverage for SE therapy. This will offer opportunities for participation in SE programs to patients with PAD. However, there is evidence that less than 20% of those referred to a supervised cardiac rehabilitation program follow-through on that referral and attend SE with adherence sufficient to garner meaningful clinical benefit. Thus, multiple approaches are needed to reduce the barriers to exercise and increase incentives for patients to increase regular physical activity.
Methods: We conducted a pilot study in 41 patients with PAD. Patients in the intervention arm were fitted with an activity monitoring device (FitBit Flex®) and given behavioral monitoring, motivational updates, and feedback regarding their exercise program. The control group wore the device with no feedback or ability to see their number of steps walked.
Results: Patients in the intervention arm walked more steps at the end of 12-weeks. Additionally, a financial incentive structure tested in the pilot study resulted in a 38–63% increase in average daily steps.
Conclusions: This pilot study revealed that activity monitoring with feedback resulted in improvement in all measured outcomes.
Poster 12
Greater exercise pressor response is associated with impaired claudication outcomes in symptomatic peripheral artery disease
1Penn State Heart and Vascular Institute, Hershey, PA, USA, 2Penn State College of Medicine, Hershey, PA, USA
In patients with peripheral artery disease (PAD), the exercise-induced rise in blood pressure (exercise pressor response; EPR) is exaggerated compared to healthy subjects. We tested the hypothesis that in patients with PAD, a higher EPR to walking is associated with worse claudication outcomes. A total of 304 symptomatic PAD patients were enrolled. Average age and ankle brachial index (ABI) were 67 ± 9, and 0.68 ± 0.22 (mean ± SD). EPR was assessed during a constant-load treadmill test (2 mph, 0% grade). Heart rate (HR) was measured by ECG, and blood pressure (BP) was measured every 2 min using a manual cuff. Subjects walked until maximal pain, or a maximum of 20 min. Additionally, claudication onset time (COT) and peak walking time (PWT) were measured during a standard, progressive, graded treadmill test, and were 186 ± 152 sec and 402 ± 237 sec, respectively. After 2 min of walking during the constant load test, HR increased 26 ± 14 beats/minute (b/min) from baseline, and systolic (SBP), diastolic (DBP), and mean arterial pressure (MAP) increased by 16 ± 2, 5 ± 16, and 8 ± 17 mmHg. Rate pressure product (RPP) increased by 5113 ± 3531 b/min x mmHg. These changes represented ≥ 86% of the peak values from the progressive test. Regression analyses showed that the increase in HR, SBP, MAP and RPP during the initial 2 min of constant-load treadmill test were negatively associated with COT after adjusting for significant covariates (p < 0.05). Similarly, HR and RPP were negatively associated with PWT (p < 0.05). We conclude that the EPR at 2 min of walking at no incline is associated with impaired claudication outcomes in patients with symptomatic PAD. EPR is an easily measured ambulatory index that can be used to assess functional impairment in PAD.
Poster 13
Study outcomes and safety of combination atherectomy in the treatment of common femoral artery disease
1Brown University, Providence, RI, USA, 2Wellspan Good Samariton Hospital, Lebanon, PA, USA
Background: Endarterectomy with or without patch angioplasty is considered gold standard for treatment of symptomatic common femoral artery (CFA) disease. Wound infection, lymph leak and hematoma are risks associated with surgical approach. Endovascular treatment has lower complications with shorter length of stay, but it achieves lower patency rates. Atherectomy with balloon angioplasty is a well-accepted alternative in patients with high risk of mortality with surgical approach. Intermediate patency rate of combination atherectomy has not been studied.
Method: In this retrospective analysis, we analyzed 2-year primary patency of CFA interventions. In the single atherectomy group, patients underwent either orbital or plaque excision atherectomy followed by focused force angioplasty with or without additional drug-coated balloon therapy. In the combination group, patients received orbital atherectomy followed by plaque excision atherectomy with focused force angioplasty with or without drug coated balloon therapy. Primary efficacy endpoint was 2-year freedom from clinically driven target vessel revascularization.
Results: A total of 47 patients underwent endovascular interventions to 61 de novo CFA lesions (40 single group and 21 combination group). Patients in both groups had similar baseline characteristics including proportion of Rutherford class. Primary endpoint was met in 27 (67.5%) patients in the single atherectomy group and 20 (95.2%) patients in the combination group with p-value = 0.01.
Conclusion: Combination atherectomy achieves higher primary patency rate at 2 years when compared with single atherectomy in the treatment of CFA disease.
Poster 14
Geographic variation in peripheral artery disease and major adverse cardiovascular and limb events among Medicare beneficiaries
1University of Minnesota, Minneapolis, MN, USA, 2Brigham and Women’s Hospital, Boston, MA, USA, 3Vanderbilt University, Nashville, TN, USA, 4Jobst Vascular Institute, Toledo, OH, USA
Background: Peripheral artery disease (PAD) is a common manifestation of atherosclerosis affecting 5% of adults and > 20% of people over the age of 70. There are known regional differences in the prevalence of coronary heart disease and stroke but variations in the prevalence of PAD and its associated complications are not well characterized. We sought to describe the geographic variation in PAD, and incident major adverse cardiovascular (MACE) and limb events (MALE) in an older adult population.
Methods: This study evaluated data from a 20% sample of Medicare beneficiaries from 2011-2014. County-level data were used to create age-adjusted, national maps representing quintiles of PAD prevalence and cardiovascular event rates in the Medicare population with and without PAD. MACE was defined as a composite of myocardial infarction, ischemic stroke or all cause death. MALE was defined as a composite of acute limb ischemia, ischemic amputation or limb revascularization.
Results: County-level PAD prevalence ranged from 0-28% with a national prevalence of 11.2%. Higher prevalence was seen in the Rust Belt, mid-Atlantic states, Texas and Florida (see P14 Figure). Patients with PAD had higher MACE (17.9 vs 6.2 events per 100 person years [PY]) and MALE (3.0 vs 0.4 events per 100 PY) than the total Medicare population. PAD patients suffered increased rates of MACE and MALE similarly across all regions.
Conclusion: PAD prevalence and associated cardiovascular outcomes vary significantly across the United States. Further research is warranted to better understand this heterogeneity and potential underlying causes including risk factors, health disparities and systems of care
Poster 15
Prevalence of brachial artery fibromuscular dysplasia - a single center study
1University of Virginia, Charlottesville, VA, USA, 2University of North Carolina, Chapel Hill, NC, USA
Introduction: The predominant arterial beds involved in fibromuscular dysplasia (FMD) are the renal and carotid arteries. The exact prevalence of brachial artery FMD is unknown. Patients with brachial FMD can present with cyanosis, paresthesia’s, digital ischemia secondary to thromboembolism or may be asymptomatic.
Methods: Data from the United States FMD registry and electronic medical records were reviewed to determine the prevalence of brachial FMD at a single tertiary referral center. Demographic data, clinical findings, and involvement of other arterial beds in patients with brachial FMD were compared with those of patients without brachial FMD. The diagnosis was made or excluded based on duplex ultrasound (US), angiographic (computed tomography angiography [CTA], magnetic resonance angiography, catheter-based angiography, intravascular ultrasound) or a combination of modalities.
Results: Sixty-six of the 214 patients in the FMD registry from a single center were evaluated for brachial FMD. Brachial FMD was diagnosed by duplex US (8/17, 47%), CTA (3/17, 18%), or a combination of US and angiographic modalities (6/17, 35%). The prevalence of brachial artery FMD was 26% (17/66), and 53% patients had bilateral brachial FMD. Patients with brachial artery FMD were more likely to be women (94% vs. 6%, p < 0.001), slightly older at the time of their initial diagnosis of FMD (mean = 55.8 vs. 50.6, p = 0.153), had FMD involvement of the external iliac artery (47% vs. 2.0%, p < 0.001), mesenteric (24% vs 2%, p = 0.004), and vertebral (47% vs 14%, p = 0.005). Fifty-three percent were symptomatic at diagnosis. There was no difference in the burden on aneurysms, dissections, or headaches.
Conclusions: Patients with brachial arterial FMD are predominantly women. They are also more likely to have external iliac artery, vertebral, and mesenteric FMD. Brachial FMD can be bilateral and asymptomatic at diagnosis in about 50% of patients.
Poster 16
Prevalence and characterization of bovine arch anomalies in patients with fibromuscular dysplasia
1Icahn School of Medicine at Mount Sinai, New York, NY, USA, 2New York Presbyterian/Weill Cornell Medical College, New York, NY, USA
Background: Fibromuscular dysplasia (FMD) is a non-atherosclerotic arteriopathy that causes stenoses, aneurysms, dissections and tortuosity. Aortic arch anomalies (AoA) – bovine arch (BA), anomalous left vertebral artery origin (ALV), aberrant right subclavian artery (ARS) – occur more frequently with thoracic aortic aneurysm and dissection than the general population and may be a marker of underlying arteriopathy. Arterial aneurysms and dissections are common in FMD patients, but the prevalence of AoA has not been described in this population.
Methods: Magnetic resonance/computed tomography angiographic (MRA/CTA) exams of the aortic arch were reviewed in patients with confirmed FMD. FMD patients with AoA were compared to two age (± 2 years) and sex-matched controls with recent (± 6 months) MRA/CTA. Those with heritable connective tissue diseases, bicuspid aortic valve, prior thoracic aortic surgery, or imaging performed for TAVR were excluded.
Results: We included 265 FMD patients and 168 controls. The majority (94%) of patients were women with mean age 53.8 ± 12 years and multifocal FMD. Overall, 84 (32%) had AoA compared to 32 (19%) in controls (p = 0.0038). The most common AoA identified in cases versus controls was BA (80% vs 62.5%, p = 0.0007), ALV origin (19% vs 28.1%, p = 0.7673) and ARS (8% vs 9.4%, p = 0.5634). Six FMD subjects had ≥ 1 AoA as compared to zero controls. The rate of aneurysms and dissections in FMD patients with AoA was 32% and 38% versus 31% (p = 0.8422) and 31% (p = 0.2498) in those without.
Conclusion: The prevalence of AoA in this FMD cohort is significantly higher than the general population. AoA may be an aortic manifestation of FMD not previously identified. Future study is needed to determine if AoA is associated with specific vascular events in patients with FMD.
Poster 17
Pregnancy outcomes in patients with fibromuscular dysplasia (FMD): Single center experience
Cleveland Clinic, Cleveland, OH, USA
Introduction: Risk of pregnancy in patients with FMD is unknown. We report clinical features and pregnancy outcomes among patients with FMD from a single center.
Methods: We conducted a retrospective chart review of patients who became pregnant following FMD diagnosis. Demographics, clinical features, and pregnancy outcomes are reported.
Results: Of 666 patients with FMD, we identified 12 with pregnancy after FMD was diagnosed. Mean age at FMD diagnosis was 29.6 years; all patients were white. FMD type was: multifocal 5/12 (41.7%), focal and multifocal 3/12 (25%), focal 2/12 (16.7%), undetermined 2/12 (16.7%). Eight pts (66.7%) had multi-vessel FMD, and 7 (58.3%) had arterial events (e.g., stroke, myocardial infarction, dissection). Eleven patients completed at least one pregnancy; One patient terminated sole pregnancy due to perceived high risk. Ten of 12 (83.3%) patients had hypertension (HTN); all had renal FMD. Among those with HTN, 5 patients were diagnosed prior to the first pregnancy, one during first pregnancy, two during subsequent pregnancies, one after pregnancy, and one was undetermined. Four of 10 (40%) patients with HTN had complicated pregnancy (preeclampsia, preterm delivery, renal angioplasty). There were no dissections, ruptured aneurysms, or other arterial events with pregnancy. There were two preterm deliveries, one resulting in neonatal respiratory insufficiency.
Conclusion: In this small series of patients with FMD who became pregnant, HTN-related complications were common. While no dissection or aneurysm ruptures occurred, it is possible that risk is underestimated as those at highest risk may have deferred or terminated pregnancy. Further studies are needed to estimate maternal and fetal risks in FMD.
Poster 18
Discrepancies in carotid duplex ultrasound study measurements among heart failure patients with left ventricular assist device (LVAD)
1Saint Vincent Hospital, Worcester, MA, USA; 2Ochsner Heart and Vascular Institute, New Orleans, LA, USA
Background: A left ventricular assist device (LVAD) has been used for many years to manage patients with heart failure (HF) either as a bridge or as destination therapy. LVAD could bluntly and significantly change the peripheral blood flow pattern that leads to alter the carotid duplex ultrasound waveforms in HF patients. The aim of this study was to evaluate the carotid blood flow pattern post-LVAD implantation.
Methods: A retrospective review of the patients with a history of LVAD implantation between 2012–2016 at Ochsner Foundation. We identified 315 patients who had pre-procedural carotid duplex ultrasound study (CDUS) as a part of their pre-procedural evaluation. Out of these 315, only 16 patients had post-LVAD CDUS; these post-LVAD studies were performed during evaluation of the probable neurological deficits. A univariate logistic regression analysis was performed.
Results: Out of 16 patients who had CDUS both pre and post LVAD implantation, five were female, and 11 were male. Mean age of the patients was 57 ± 10.3 years. One Heartmate III, 12 Heartmate II, and three Heartware HVADs were implanted in our patients. Pre-LVAD stenosis was reported < 40% in 12 patients and < 20 % in 3 patients at both the right and left ICA. One pre-LVAD patient had < 50% stenotic lesion at right ICA and < 40% at the left ICA. Post-LVAD stenosis was noted to decrease from < 40% to < 20% in eight patients but it was not statistically significant, p = 0.19. There were no changes noted in pre-and post-LVAD percent stenosis among the remaining eight patients. We observed a decrease in the mean PSV both at CCA and ICA, p < 0.001. An increase in the mean EDV was seen both at CCA and ICA, p = 0.0013 The Doppler velocity waveforms in post LVAD patients were found to be blunted as compared to the pre-LVAD waveforms. See P18 Table.
Conclusion: Our study demonstrates a trend towards change in peak systolic and ends diastolic velocity and waveform morphology among LVAD patients LVAD. Nevertheless, it didn’t change the carotid stenosis percentage significantly. Large studies are warranted to determine accuracy and validity of CDUS using velocity and waveform based criteria among heart failure patients with LVAD.
Comparing pre- and post-LVAD PSV and EDV.
LVAD, left ventricular assist device; CCA, common carotid artery; ICA, internal carotid artery.
Poster 19
Six-minute walk performance as a predictor of lower extremity events in people with peripheral artery disease
1University of Illinois at Chicago College of Medicine, Chicago, IL, USA, 2University of California San Diego, La Jolla, CA, USA, 3National Institutes of Health, Bethesda, MD, USA, 4University of Maryland School of Medicine, Baltimore, MD, USA, 5University of North Carolina School of Medicine, Chapel Hill, NC, USA, 6University of Chicago, Chicago, IL, USA, 7Stanford University, Stanford, CA, USA, 8Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Background: Among people with lower extremity peripheral artery disease (PAD), this longitudinal study assessed whether poorer 6-minute walk performance at baseline was associated with a higher rate of lower extremity adverse events during follow-up.
Methods: Consecutive patients with PAD from Chicago-area medical centers were enrolled. Participants underwent baseline 6-minute walk testing and returned for annual study visits for up to four years. The ankle brachial index (ABI) was measured at baseline and at each annual follow-up visit. Participants were interviewed to identify lower extremity revascularizations, amputations, and hospitalizations for critical limb ischemia during follow-up. Medical record review was performed to confirm reported outcomes. A lower extremity event was defined as one or more of the following: ABI decline > 0.15, lower extremity revascularization, amputation, or hospitalization for critical limb ischemia.
Results: Of 369 PAD participants enrolled (mean age 69.4 ± 10.0 years, mean ABI 0.67 ± 0.17, 31% women, 30% black), 108 (29%) developed a lower extremity event during the study duration. The mean (SD) duration to the final follow-up visit was 33.3 (16.5) months. Mean age was 68 (10.8) years among those with lower extremity events and 69.9 (9.6) years among those without events during follow-up. Mean ABI values were 0.66 (0.18) and 0.70 (0.15), respectively, at baseline. The table shows associations of 6-minute walk tertiles with subsequent lower extremity events, adjusting for age, sex, race, ABI, comorbidities, smoking, and BMI. See P19 Table.
Conclusions: Among people with PAD, poorer 6-minute walk performance at baseline is associated with higher subsequent rates of adverse lower extremity events.
Associations of 6-minute walk with subsequent lower extremity event rates in people with PAD.
HR, hazard ratio; CI, confidence interval; ABI, ankle-brachial index; CLI, critical limb ischemia; PAD, peripheral artery disease.
Poster 20
Associations of weight change with calf muscle characteristics and functional decline in adults with peripheral artery disease
1University of Chicago, Chicago, IL, USA, 2Stanford University, California, USA, 3University of California San Diego, La Jolla, CA, USA, 4National Institute on Aging, Baltimore, MD, USA, 5University of Maryland, Baltimore, MD, USA, 6University of North Carolina, Chapel Hill, NC, USA, 7Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Background: In peripheral artery disease (PAD), obesity is associated with adverse calf muscle characteristics and functional decline. Associations of weight loss or gain with changes in calf muscle characteristics or functional decline are unknown.
Methods: Participants were 311 men and women with an ABI < 0.90 who underwent baseline testing between 2002 and 2004. Mean follow-up was 3.4 years. Weight change categories were weight loss (≥ 5 lbs/yr at ≥ 1 visit), stable (weight change < 5 lbs at all visits), and gain (≥ 5 lbs/yr at ≥ 1 visit). Weight loss was classified as ‘intentional’ or ‘unintentional’. Six-minute walk distance (6MWD) was measured at baseline and annually. Calf muscle area and percent fat were measured with CT at baseline and every 2 years. Associations of weight change categories with changes in calf muscle characteristics and 6MWD were analyzed using mixed-effects models, accounting for correlations among successive annual differences in outcomes. We also adjusted for age, race, sex, ABI, smoking, comorbidities, physical activity, lower extremity revascularization, or hip/knee replacement during follow-up.
Results: Mean age was 74.8 ± 7.8 years and mean ABI was 0.63 ± 0.16. Adults who lost weight had the greatest annualized decrease in muscle mass, smallest increase in percent muscle fat, and the smallest decline in 6MWD (p trend < 0.001) (see P20 Table). Functional decline was significantly less in adults with intentional vs unintentional weight loss.
Conclusions: Despite losing muscle mass, adults with PAD who lost ≥ 5 lbs had less functional decline than adults whose weight was stable or increased. Functional decline was significantly less in adults with intentional vs unintentional weight loss.
Associations of changes in weight with changes in calf muscle characteristics and functional decline among adults with peripheral artery disease, 2002-2009.
p value for trend < 0.001 **p value for trend = 0.02, ***p value for trend=0.2, †pairwise p-value = 0.02, ‡pairwise p value of intentional vs unintentional weight loss = 0.01.
BMI, body mass index; CI, confidence interval, 6MWD, 6-minute walk distance, NA, not applicable.
Clinical Science / Epidemiology: Imaging
Poster 21
Is routine duplex ultrasonography following carotid endarterectomy worthwhile?
1St James’s Hospital, Dublin, Ireland, 2RCSI Bahrain, Al Muharraq, Bahrain
Introduction: Neither European nor American Vascular Societies provide recommendations based on a high level of evidence for duplex ultrasound (DUS) surveillance after carotid endarterectomy (CEA). With this in mind, the aims of our study were to determine the rates of restenosis and significant contralateral disease progression after CEA, to determine the number of patients who underwent further intervention based on post-operative surveillance and to estimate the cost of duplex ultrasound (DUS) surveillance after CEA.
Methods: All patients who underwent a CEA from 2005 to 2010 were included. Imaging records were evaluated for numbers of post-operative duplex scans, development of ipsilateral restenosis and interval progression of contralateral disease. Operative records were investigated for further carotid interventions. The costs of the DUS surveillance programme over this period were estimated.
Results: A total of 209 patients were analyzed, 132 of whom had a CEA for symptomatic disease. Overall, 1271 post-operative carotid duplexes were performed, an average of six per patient. The rates of restenosis and significant contralateral disease progression were 16% and 5%, respectively. Ten further revascularisation procedures were performed on asymptomatic patients who developed significant stenoses on post-operative surveillance, six for recurrent ipsilateral disease and four for contralateral progression. Based on an estimated cost of 100 Euros per DUS, this amounts to a cost of 127,100 Euros ($155,204 US) for a surveillance programme that resulted in ten subsequent interventions.
Conclusion: The cost of routine surveillance is high and is difficult to justify in the setting of limited resources.
Poster 22
Ultrasound-derived flow volume is a predictor of functional status of newly created hemodialysis arteriovenous fistulas
1Mayo Clinic Rochester, Rochester, MN, USA, 2Kingman Regional Medical Center, Kingman, AZ, USA
Introduction: The aim was to study the role of flow-volume measurement as a predictor of functional status in newly created arteriovenous fistulas (AVFs) and to assess its correlation with stenosis.
Methods: In this retrospective, IRB-approved study we searched our radiology database from January 2012 to July 2013 for patients who underwent ultrasound (US) evaluation at 4-6 weeks after AVF creation as part of routine follow-up. US was performed to assess presence, location, and severity of stenosis, and flow-volume measurements (averaged over three locations in the outflow) were obtained. Medical charts were reviewed for data on clinical AVF maturity and timing of hemodialysis initiation using the AVF. AVFs were grouped into “mature” and “non-mature” categories, based on clinical assessment and ability to successfully initiate hemodialysis at the anticipated time.
Results: 75 patients (44 men, mean age 64.9 years, 65 upper arm AVFs, 10 forearm AVFs) were included and were matched for coronary artery disease, diabetes, hypertension, and obesity. 50 patients had mature AVFs. Mean flow was significantly higher in mature fistulas compared to non-mature fistulas (1374 vs 636 mL/min, p < 0.0001), while stenosis rate (40% vs 52%, p = 0.32), peak systolic velocity at stenosis site (475 vs 466 cm/s, p = 1.0) and systolic velocity ratio (2.7 vs 2.6, p = 0.95) were not significantly different. A threshold of flow > 775 mL/min had a sensitivity of 83.3% and specificity of 85.7% to predict fistula maturation.
Conclusions: Newly placed maturing AVFs have higher flow than non-maturing fistulas, and flow is a better predictor for fistula maturation than presence and severity of stenosis.
Poster 23
Reproducibility of a novel invasive method of measuring conduit and microvascular arterial vascular function
VA Boston Healthcare System, Boston, MA, USA
Background: Muscle fatigue is a commonly reported symptom of Gulf War Illness and may be related to vascular changes resulting from environmental exposures encountered by Veterans during the Gulf War.
Hypothesis: We assessed within-observer reproducibility of a novel method of measuring endothelium-dependent conduit and microvascular vasomotor function using arterial catheterization and intravascular ultrasound and Doppler flow wire in the profunda femoral artery.
Methods: In 20 enrolled Veterans, we measured blood flow response to intraarterial infusions of 10-6 M acetylcholine (ACh), adenosine, and nitroglycerin (NTG). Two researchers blinded to infusion stages measured luminal cross-sectional area (CSA) and area under the curve of flow velocity waveforms several weeks apart using ImageJ (NIH). Change in volume flow from baseline to ACh (endothelium-dependent) and adenosine (endothelium-independent) estimated microvascular function. Change in CSA from baseline to ACh and NTG estimated conduit function. We assessed within-observer variability by interclass correlation coefficients (ICC) and Bland-Altman analyses using Stata 14.2 (StataCorp).
Results: The majority were male (91%) with mean age of 55 years, had history of hypertension (52%), diabetes (10%), hyperlipidemia (chol> 250 mg/dL; 40%), and were past or current smokers (76%). All Veterans tolerated study procedures with no adverse events. The P23 Table summarizes mean absolute values at baseline and changes compared to baseline expressed as mean bias, limits of agreement, and ICC for first and second measures.
Conclusions: Excellent reproducibility was seen in CSA, flow velocity and volume, conduit endothelial-dependent function, and microvascular endothelium function. Conduit endothelium-independent function had moderate reproducibility.
LOA, limits of agreement; ICC, interclass correlation coefficient; CSA, cross-sectional area; ACh, acetylcholine.
Clinical Science / Epidemiology: Other
Poster 24
Intersocietal Accreditation Commission (IAC) Quality Improvement Self-Assessment Tool utilization improves accreditation outcomes
1Intersocietal Accreditation Commission, Ellicott City, MD, USA
Introduction: The aim was to evaluate the effect of the Intersocietal Accreditation Commission (IAC) Quality Improvement (QI) Self-Assessment Tool utilization on subsequent accreditation decision by facilities applying for IAC vascular testing accreditation.
Methods: Variables measured included: application date, testing area (extracranial, venous, arterial, visceral, and overall), accreditation decision, date the first assessment, and self-assessment completed before application submission.
Results: 635 facilities applied for accreditation from 2016-2017. Of those, 192 (30.2%) completed at least one assessment and 128 (20.2%) completed an assessment prior to submitting an accreditation application.
Quality issues were identified at 575 (90.6%) facilities. Although not significant, facilities that used the assessment before applying for accreditation had fewer quality issues than those that did not utilize the tool (87.5% vs. 91.3%, p = 0.126).
Evaluating the data by testing area, there was a significant decrease in the number of facilities with quality issues for facilities that utilized the tool for venous testing (67.0% vs. 80.2%, p.004) and visceral testing (66.7% vs. 81.4%, p = 0.048). Although not significant, there was a similar trend for extracranial testing (48.7% vs. 53.2%, p = 0.221) and arterial testing (73.9% vs. 78.4%, p = 0.141).
Facilities applying for venous accreditation that utilize the tool are 3.8 times more likely to be granted accreditation (p = 0.004) than those facilities that did not use the tool. See P24 Figure.
Conclusion: An early evaluation of vascular testing facilities demonstrates that utilization of the IAC QI Self-Assessment Tool has a positive effect on the identification and correction of quality issues before submission leading to positive accreditation outcomes.
Poster 25
How accurate is physical examination for the diagnosis of lymphedema of the lower extremities? A lymphoscintigraphic study
Hospital Privado Universitario de Córdoba, Córdoba, Argentina
Background: Early identification of lymphedema is paramount for optimal treatment outcomes and requires a high index of suspicion. The aim of this study was to assess the accuracy of clinical signs for the diagnosis of lower extremities lymphedema in a cohort of patients evaluated with lymphoscintigraphy.
Methods: Patients evaluated for suspected lymphedema by the Vascular Medicine Service who underwent lymphoscintigraphy from 2008 to 2017 were retrospectively analyzed. Patients with BMI > 50 kg/m2, amlodipine treatment, and advanced-stage lymphedema were excluded. Reported signs were categorized into presence/absence of Stemmer sign (SS), thickening of skin [dorsum of foot] (ToS), squaring (toes) and Godet sign. Lymphoscintigraphies were assessed by three experts, unaware of the clinical findings, according to the presence of asymmetric node uptake and/or dermal backflow, delayed transit time of the radiolabeled colloid to the regional lymph nodes and/or formation of collateral lymphatic channels. A positive lymphoscintigraphy plus a consistent history of lymphedema were considered a confirmed diagnosis. See P25 Table.
Results: 99 patients were included: 73 women, BMI 29.09 ± 6.5 (mean ± SD), ages 16–88 (54 ± 17). Twenty-one patients had secondary lymphedema.
Conclusion: SS and squaring of the toes were the most specific clinical signs of lymphedema. ToS was the most sensitive sign. Godet sign showed a high likelihood ratio (LR-). These findings would contribute to improve the assessment of patients with peripheral edema.
SS, Stemmer sign; ToS, thickening of skin; PPV, positive predictive value; NPV, negative predictive value; LR, liklihood ratio.
Poster 26
MUSICWALKER: A music-guided, home-based claudication rehabilitation program
University of Illinois at Chicago, Chicago, IL, USA
Introduction: We previously demonstrated that using rhythmic auditory stimulation (RAS) to accentuate the beat and increase the tempo of music immediately increased walking distance and distracted from pain in patients with claudication. We hypothesized that an RAS-enhanced, music-guided, home-based walking exercise program would result in greater 6-minute walking distance (6MWD), compared to a no-music home-based walking program at 12-weeks.
Methods: Participants (n = 16) with claudication (men = 13, age = 65.8 (7.2) years, ABI = 0.62 (0.16)) randomized to RAS-enhanced music guided home-based walking program (n = 12) or a no-music home-based walking program (n = 4), 3 times/wk for 60 minutes. The exercise prescription was individualized and used the same parameters for both groups. The only difference was the use of the RAS-enhanced music to guide walking in one group and not the other. Mixed effects regression was used to model group differences in change from baseline.
Results: The RAS group showed greater change in 6MWD (mean difference 76 m, 95% CI 37–115 m, p ≤ 0.001) and in onset to claudication distance (mean difference 109 m, 95% CI 7–210, p = 0.04) compared to the no-music group. Adherence to training was 89% (RAS) and 61% (no-music). Measures of physical function, pain interference, and mental health were improved in the RAS-group. See P26 Table.
Conclusion: A RAS-enhanced music exercise training program improved objective and subjective walking ability compared to a traditional home-based exercise group. It is feasible to purposefully design a home-based exercise program for claudication by using the rhythmic and distractive properties of music to guide, facilitate, and progress exercise while maintaining a high level of adherence.
Results.
6MW, 6-minute walking distance; OCD, onset to claudication distance; WIQ, walking impairment questionnaire; PADQOL, peripheral artery disease quality of life questionnaire; B-6, baseline to 6-six-week follow-up; B-12, baseline to 12-week follow up; P, mixed effect regression interaction test for mean group difference in change from baseline.
Poster 27
Correlation of clinical staging of lymphedema, bioimpedance spectroscopy analysis and interlimb measurement difference among breast cancer-related lymphedema
St. Luke’s Medical Center - Global City, Taguig City, Philippines
Breast cancer-related lymphedema (BCRL) is one of the most frequent causes of lymphedema. Bioimpedance spectroscopy analysis (BSA) quantifies the extracellular fluid in the patient’s arm. BSA was determined using lymphedema index (L-Dex) ratio, −10 to +10 defines the normal range for patients without lymphedema. This is a cross-sectional study design correlating the clinical staging of lymphedema with BSA value and interlimb measurements among BCRL. A total of 151 patients were included in the study. There were 150 females (99.3%) and one male (0.7%) with BCRL. The majority of patients were in clinical stage 1 (45%). The mean L-Dex ratio was 46.82 with a mean interlimb difference of 3.21 cm. Deep venous thrombosis was noted in 2.8% of the study population. The clinical stage of lymphedema is significantly correlated with the BSA value (p ≤ 0.001). With an increasing clinical stage of lymphedema, there is corresponding increase in the proportion of BSA value. As the interlimb cirumference difference increases, L-Dex ratio value also increases (p ≤ 0.001). BSA produces a reliable Results in the assessment of lymphedema. The routine use of venous compression ultrasound of the affected limb can be beneficial as part of screening.
Clinical Science / Epidemiology: Thrombosis and Hemostasis
Poster 28
Evaluation of pharmacist-led transition of care for warfarin management
ProMedica Toledo Hospital, Toledo, OH, USA
Background: The most vulnerable time for patients started on warfarin occurs during their transition from the hospital to outpatient management. Dosing errors, insufficient monitoring, and medication non-adherence occur during this time. Implementing pharmacist-led counseling (PLC) prior to discharge can prevent inappropriate treatment. This study evaluated effectiveness of transition of care before and after implementing PLC.
Method: In an anticoagulation clinic at a tertiary medical center, patients were evaluated before and after the implementation of PLC. Patients admitted to the hospital, new to warfarin, and referred by vascular physicians were included. The primary outcomes were the average time between the referral and the first contact with the patient, and the rate of inappropriate dosing and delayed treatment. The secondary outcome is the rate of hospital readmission due to clotting or bleeding within 30 days after discharge.
Results: A total of 68 patients were included in this study. The mean ± SD time between the referral and first contact with patients was 58.7 ± 57.8 hours before PLC was implemented and 25.1 ± 31.7 hours (p value < 0.01) after PLC implementaiton. The rate of anticoagulation therapy discrepancies in the pre-intervention group and post-intervention group was 38.8% and 13.3%, respectively (p = 0.059). The rate of readmission within 30 days in the pre-intervention group and post-intervention group was 0% and 6.7%, respectively (p = 0.234).
Conclusion: PLC prior to discharge decreases time to appropriate treatment during patient’s transition from the hospital to ambulatory care.
Poster 29
Pulmonary embolism severity index predicts six minute walk distance after pulmonary embolism
Loyola University Medical Center, Maywood, IL, USA
Background: Pulmonary embolism (PE) is associated with significant morbidity, mortality and long term functional limitation. Determinants of functional limitation after PE are unknown.
Methods: From a single center tertiary care PE database, we retrospectively analyzed patients who underwent evaluation by the pulmonary embolism response team (PERT) from 2015-2017. PE patients who underwent 6-minute-walk test (6MWT) prior to discharge were included. Pulmonary Embolism Severity Index (PESI) score was calculated using baseline clinical and demographic characteristics.
Results: Among a total of 129 patients evaluated by PERT, 39 (30%) underwent 6MWT. Of those, 15.4%, 82.1%, and 2.6% of patents were classified as low risk PE, submassive PE, and massive PE, respectively. Thirty-three precent underwent catheter-directed thrombolysis. Mean age was 57.9 ± 12.9 years, 56.4% were white, 43.6% were female, mean BMI was 35.2 ± 9.4kg/m2, and mean PESI score was 92.6 ± 32.5. Rising PESI score was significantly associated with decrease in 6MWT distance. For each 10-point rise in PESI score, 6MWT distance decreased by 41.7 ft (p = 0.056), r = 0.31. See P29 Figure.
Conclusion: After acute PE, an increase in PESI score is associated with substantial decrease in functional capacity as measured by 6MWT distance. Future studies evaluating efficacy of therapies for PE should incorporate baseline PESI scores when assessing functional outcomes.
