Abstract
Authors will present posters based on the following abstracts at the 26th SVM Scientific Sessions. Sessions will be held June 11–13, 2015 at the Baltimore Marriott Waterfront Hotel in Baltimore, Maryland. Poster presentations will occur on Thursday, June 11 at 4:00 p.m.
In honor of 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 Presentation Luncheon that will be held on Thursday, June 11 at 12:15 p.m.
The winners of the Jay D. Coffman Young Investigator Award will be announced prior to the close of the annual meeting.
For more information about the meeting visit: www.vascularmed.org
Basic Science – Angiogenesis/Vasculogenesis YIA 1
Cyclin-Dependent Kinase Inhibitor 2B Regulates Transforming Growth Factor Beta 1 Mediated Smooth Muscle Cell Recruitment to Ischemic Blood Vessels
Vivek Nanda1, Kelly Downing1, Yoko Kojima1, Daniel DiRenzo1, Jessie Dalman1, Andrew J Connolly1, Lars Maegdefessel2, Ljubica Perisic2, Sonny Dandona3, Liang Guo4, Harry R Davis4, Renu Virmani4, Joshua Spin1, Nicholas Leeper1
1Stanford University School of Medicine, Stanford, CA, USA; 2Karolinska Institute, Stockholm, Sweden; 3McGill University, Montreal, QC, Canada; 4CVPath Institute, Gaithersburg, MD, USA
Peripheral artery disease (PAD) is a highly morbid condition affecting about 8.5 million Americans. Genetic variation at the chromosome 9p21 cardiovascular (CV) risk locus has been associated with PAD. However, it is unknown whether this association is secondary to atherosclerosis or is the result of a separate angiogenesis related mechanism. Quantitative ultrastructural analysis of human plaque samples revealed that carriers of the 9p21 risk allele (RA) display a significantly increasing burden of immature intraplaque microvessels than carriers of the ancestral allele. To determine whether this phenotype is independent of atherosclerosis, we performed femoral artery ligation surgery in mice lacking Cdkn2b; a candidate gene associated with reduced expression in carriers of the 9p21 RA. These mice developed advanced hind-limb ischemia and digital auto-amputation, relative to wild type controls. Subsequent in situ and in vitro hypoxic assays found this to be a consequence of pro-angiogenic behavior displayed by endothelial cells (EC) and impaired smooth muscle cell (SMC) recruitment to the developing neovessel. Microarray revealed that such a defect is a result of enhanced TGFβ1 signaling. Molecular signaling studies identified this increase to be a consequence of impaired expression of SMAD7, a known inhibitor of TGFβ1 signaling. Further, increasing TGFβ1 signaling was ultimately found to manifest the upregulation of a poorly studied effector molecule, TGFβ1-induced-1, previously known to have antagonistic effects on the EC and SMC. Taken together these findings suggest that loss of CDKN2B may not only promote CV disease, but may also impair TGFβ1 mediated hypoxic neovessel maturation, ultimately resulting in PAD.
Basic Science – Endothelial Function and Surrogate Markers YIA 2
Renal Impairment Negatively Affects Venous Endothelial Dysfunction
Daniel E Kendrick1, Adam R Wheeler1, Alfred Hausladen2, Andre F Gosling1, Ann H Kim1, Henry R Baele1, John C Wang1, Vikram S Kashyap1
1University Hospitals Case Medical Center, Cleveland, OH, USA; 2Institute for Transformative Molecular Medicine, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, USA
Introduction: Chronic kidney disease (CKD) has been shown to significantly increase cardiovascular risk. We sought to compare NO mediated venous endothelial dysfunction (ED) in vein segments harvested from control (CON) patients with renal function >60 GFR compared to those with CKD with a mean GFR of 30.8.
Methods: Saphenous vein was harvested from patients undergoing amputation or lower extremity bypass. 4 mm vein rings were mounted on force transducers. Segments were mounted in 37° oxygenated Krebs solution and maximally contracted using KCl. NE was used to achieve submaximal contraction. EDR was determined using increasing concentrations of bradykinin (BDK). Endothelial independent relaxation was confirmed using sodium nitroprusside. Two-way ANOVA was used to analyze differences between harvest technique across BDK concentration. Paired t-test was used to examine nitrate/nitrite (NOx) levels.
Results: We compared 45 rings in 18 patients: 22 rings from 8 controls vs 23 rings from 10 CKD patients. Normal function patients achieved increased relaxation to maximal BDK concentration [10–6 M]; (50.9% CON vs 36.8% CKD, p = 0.029). Analysis by two way ANOVA for mean % relaxation for BDK concentration [10–11 – 10–6 M] showed improved EDR in CON samples compared to CKD (p = 0.0002). Mean nitrite tissue bath concentration measurements post-BDK increased in both cohorts (CON) 102.4 ± 128.7 nM (p = 0.044) vs (CKD) 58.1 ± 67.3 nM (p = 0.032). Histology and IHC confirmed intact endothelium by morphometric analysis and CD31 staining.
Conclusion: Venous endothelial function is compromised in the setting of renal impairment. Inferior bypass outcomes observed in patients with renal failure may be partially explained by these findings.
EDR in CON vs. CKD vein segments.
Clinical Science/Epidemiology – Arterial and Aortic Disease YIA 3
Significantly Increased Collagen Quantification on Histological Confirmation of High-Risk Carotid Plaque and Correlation with Microembolic Signals During Endarterectomy
Jennifer Li1, Daniel Alicea2, Chiara Giannarelli2, Christian Pina3, Venkatesh Mani4, Prakash Krishnan2, Ageliki Vouyouka1, Rami Tadros1, Errol Gordon3, Juan Badimon2, Zahi Fayad4, Peter Faries1, Jose Wiley2
1Department of Vascular Surgery at Mount Sinai, New York, NY, USA; 2Cardiovascular Research Institute at Mount Sinai, New York, NY, USA; 3Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4Translational and Molecular Imaging Institute at Mount Sinai, New York, NY, USA
Background: The management of carotid stenosis must balance the benefits of surgical and endovascular intervention against the risks of peri/post-operative cerebrovascular events. The pre-operative identification of high-risk plaque characteristics with MRI may assess embolic potential, and these findings correlated with transcranial Doppler detection of intra-operative microembolization rates and confirmed with plaque histology.
Methods: 75 patients (symptomatic, stenosis >50%; asymptomatic, stenosis >70%) undergoing CEA will be enrolled. A pre-operative Mini-mental Status Exam, carotid MRI, and cerebral diffusion-weighted MRI are obtained one week prior to intervention. All MRI are performed with 3T MR system, carotid plaque are classified according to AHA criteria. Intraoperatively, transcranial Doppler is performed to monitor for microembolic signals (MES), detected as high-intensity unidirectional transient signals. Plaque specimen is analyzed histologically for collagen and necrotic core quantification and CD68, CD34, and actin markers. A post-operative DW-MRI and MMSE are performed within 72 hours to examine for microinfarcts and changes in neurocognitive function.
Results: Preliminary results with 16 carotid endarterectomy patients demonstrate highest generation of MES during the post-operative phase for both AHA Class VI (high-risk, 19% of total MES) and Class I-V (low-risk, 30% of total MES) plaque as identified pre-operatively with Carotid MRI. No significant difference in total MES generated has been found (p = 0.65); however, Class VI plaque has significantly higher average collagen quantification on histological analysis compared to low-risk plaque (28.2%:14.6%, p = 0.022). No significant difference on MMSE has been found (p = 0.52).
Conclusions: Preliminary results suggest that high-risk AHA Class VI carotid plaque are reliably identified by MRI and demonstrate significantly increased collagen quantification on histological analysis after endarterectomy.
Clinical Science/Epidemiology – Arterial and Aortic Disease YIA 4
Fibromuscular Dysplasia: Single Tertiary Care Center Experience
Aditya M Sharma, Bryan Kline, Sushma Madala, Lawrence McDermott, Ray Norby, Shetal Patel, Andrew Southerland, Mary Lee Jensen, Nina Solenski, John Angle, Alan Matsumoto
University of Virginia, Charlottesville, VA, USA
Introduction: Fibromuscular dysplasia (FMD) is a rare disease and there is still limited understanding of patient characteristics, clinical manifestations, imaging findings and outcomes.
Methods: Retrospective chart review was performed on 255 patients with FMD seen in a single institution from January 2009 to June 2013. Demographics, clinical features, family history, past medical history, presenting symptoms, vascular imaging and outcomes were reviewed.
Results: Most patients were women (86.3%). Mean age at first symptom and diagnosis of FMD were 54.9 and 57.9 years, respectively, with lag time between first symptoms and diagnosis being 3 years. Men were slightly older (62.4 years vs 57.9 years in women) at the time of diagnosis. Family history was significant for hypertension (HTN) (28.8%), stroke (25.1%), and aneurysms (12.2%). 70.9% of patients had HTN and mean age of HTN onset was 43.8 years. 36.9% had headache, with 52.1% being migraine-type headaches. 41.2% had a smoking history. Most common presenting symptoms were HTN (38.4%), headache (38.0%), and aneurysm (33.3%). Among women, headache (44.1%) was most the common presenting symptom and HTN (68.6%) in males. FMD was seen commonly in extracranial carotid (52.5%), renal (46.7%), and vertebral arteries (25.9%). However, men had more renal artery involvement (51.4%). 34.9% of the patients received head to pelvis imaging, and 52% and 28.1% had FMD in at least 2 and 3 vascular beds, respectively. Aneurysms and dissections were reported in 29.8% and 9.8%, respectively. Mortality was 6.3% (11.4% in males vs 5.2% in women), and subarachnoid hemorrhage was the most common cause of death.
Conclusion: This study suggests there is greater cerebrovascular involvement, and a higher mortality and aneurysm rate than reported previously; however, this could be related to referral bias to our tertiary care center.
Clinical Science/Epidemiology – Arterial and Aortic Disease YIA 5
Change in Carotid Duplex Ultrasound Velocities after Aortic Valve Replacement for Aortic Stenosis
Omair Javed, Ellen Brinza, Deborah Hornacek, Juliana Conic, Heather L Gornik, Esther SH Kim
Cleveland Clinic Foundation, Cleveland, OH, USA
Introduction: Carotid duplex ultrasonography (CDU) is frequently performed as part of the pre-operative assessment for patients with severe aortic stenosis (AS) prior to aortic valve replacement (AVR). Severe AS can result in a parvus et tardus pattern on CDU Doppler waveforms; however, the degree to which severe AS affects CDU velocities is not well characterized. We aimed to determine the changes in CDU velocities in the internal carotid arteries (ICA) of patients with severe AS before and after AVR.
Methods: We queried the Non-Invasive Vascular Laboratory database at our institution for all patients with severe AS who had both a CDU and echo pre- and post-AVR from 1/1/2005 to 5/30/2011. Patients were included if the pre- and post-AVR CDUs were within 12 months of each other and excluded if CEA was performed at the time of AVR. Stata software was used to perform all statistics.
Results: Of the 4173 patients who had both a CDU and echo within one year during the years queried, 92 patients met all other inclusion criteria. Mean age was 72.2 years, 71.7% were men. Mean aortic valve area by continuity was 0.79 ± 0.24 cm2, mean time from pre- to post-AVR CDU was 182.2 ± 98.4 days. 10.9% of patients have AVR alone, 50.0% had AVR + CABG, 12.0% had multivalvular surgery, and 27.1% of patients had AVR + other procedure (aorta repair, ablation, ASD repair). Post-AVR, there was a significant change in aortic valve peak and mean gradients but no significant change in ICA PSV or EDV bilaterally (Table).
Conclusion: There is no significant change in ICA velocities post-AVR in patients with severe AS. CDU continues to be a valid tool for assessment of ICA stenosis even in patients with hemodynamically significant AS.
Changes in Carotid Duplex and Echo Parameters After AVR.
Clinical Science/Epidemiology – Arterial and Aortic Disease YIA 6
Long-Term Comparative Clinical Outcomes of Patients with Peripheral Artery Disease with and without Concomitant Coronary Artery Disease
Debbie C Chen1, Gagan D Singh1, Ehrin J Armstrong2, Ezra A Amsterdam1, John R Laird1
1University of California, Davis, Sacramento, CA, USA; 2University of Colorado and VA Eastern Colorado Healthcare System, Denver, CO, USA
Background: There are limited contemporary data on guideline-directed medical therapy (GDMT) utilization and long-term clinical outcomes in patients with concomitant peripheral artery disease (PAD) and coronary artery disease (CAD: myocardial infarction / history of CAD) vs PAD alone.
Methods: From 2006 to 2013, 1166 patients underwent diagnostic angiography or therapeutic endovascular intervention for PAD at a multidisciplinary vascular center. We analyzed baseline demographics, clinical data, and long-term outcomes of these patients. GDMT use was assessed at the time of angiography and all-cause mortality was determined during 5 years of follow-up.
Results: 612 (52%) patients had PAD + CAD and 554 (48%) had PAD only. Patients with symptomatic PAD comprised a majority of the total cohort: claudication 34% of patients and critical limb ischemia 41%. Despite higher adherence to GDMT (all p ⩽ 0.0001) for the use of aspirin (81% vs 57%), angiotensin converting enzyme inhibitor (64% vs 52%), statin (86% vs 67%), and beta blocker (71% vs 38%), patients with PAD + CAD had a higher 5-year unadjusted rate of all-cause mortality (HR 1.9, 95% CI 1.5–2.4, p = 0.0001; Figure). Patients with PAD + CAD had more baseline comorbidities including heart failure (33% vs 11%, p = 0.0001), end-stage renal disease (17% vs 8%, p = 0.0001), diabetes (51% vs 41%, p = 0.001), and hypertension (89% vs 79%, p = 0.0001). After multivariate analysis to adjust for comorbidities, PAD + CAD remained a significant risk for mortality (HR 1.4, 95% CI 1.09–1.8, p = 0.009).
Conclusions: In this contemporary patient cohort, PAD + CAD was associated with higher long-term all-cause mortality compared to PAD alone, despite increased rates of GDMT utilization.
Basic Science – Angiogenesis/Vasculogenesis Poster 1
Elevated Circulating Levels and Endothelial Expression of Angiopoietin-2 in Humans with Continuous Flow Left Ventricular Assist Devices is Associated with Increased Angiogenesis
Corey E Tabit, Gene H Kim, Savitri E Fedson, Gabriel Sayer, Valluvan Jeevanandam, Nir Uriel, James K Liao
The University of Chicago Medical Center, Chicago, IL, USA
Arteriovenous malformations (AVMs) are common in patients with CF-LVADs and are associated with significant morbidity. The etiology of these AVMs is not clear and may reflect LVAD-induced deregulation of angiogenesis. Angiopoietin-2 (Ang-2) is a potent stimulator of angiogenesis produced by endothelial cells. This study aims to evaluate the differences in Ang-2 expression in both the serum and endothelium of patients with LVADs compared to patients with stable heart failure (HF) or heart transplantation (OHT). Blood samples were obtained from 72 patients (n= 20 HF, 38 LVAD, 14 OHT) undergoing routine heart catheterization. Human umbilical vein endothelial cells (HUVECs) were incubated on Matrigel with serum from these patients and tube formation was measured by microscopy. Serum Ang-2 levels were measured by ELISA. Vena caval endothelial cells were isolated from patients using a modified Colombo Method and Ang-2 expression was measured by quantitative immunofluorescence. Serum from patients with LVADs induced an increase in tube formation as compared to HF and OHT (84.3±15.5, 59.2±10.8, 59.8±8.2 tubes per LPF, respectively, p<0.01). Serum levels of Ang-2 were significantly increased in patients with LVADs as compared to HF and OHT (12.3±9.6, 4.5±2.1, 4.9±2.0 ng/mL, respectively, p<0.05). Ang-2 expression was higher in freshly isolated endothelial cells from patients with LVADs as compared to HF or OHT (56.3±14.1, 31.3±4.2, 35.0±11.2 AU, respectively, p<0.05; Figure). Our data suggest that factors in the blood of patients with LVADs can promote angiogenesis. Ang-2 is elevated in both the blood and endothelium of these patients and may be responsible for these findings.
Basic Science – Endothelial Function and Surrogate Markers Poster 2
Balancing Innate Immunity Activation and Death Signals for Vascular Regeneration
Frank Ospino1, Palas Chanda1, John Cooke1, Donna Wu1, William Kaiser2, Edward S Mocarski2, Nazish Sayed1
1Houston Methodist Research Institute, Houston, TX, USA; 2Emory University, Atlanta, GA, USA
Our recent discoveries have shown that innate signaling supports effective nuclear reprogramming (Lee & Sayed et al., Cell) and transdifferentiation to ECs (Sayed et al., Circulation). By activating innate immunity (via TLR3), viral vectors used for reprogramming cause global epigenetic changes that favor an environment conducive for reprogramming. Indeed, activation of innate transcription factors (TFs) enhances EC regeneration; however, activation of the same pathway could induce: (1) apoptosis via activation of Casp8; and (2) programmed necrosis by receptor-interacting protein kinase 3 (RIP3), when Casp8 is absent. We speculate that death pathways that are activated by these TFs compromise reprogramming. We previously showed that disruption of Casp8 led to mid-gestational death of mice due to unleashing of RIP3-dependent death pathways, preventing the formation of vascular endothelium and hematopoietic cells. By contrast, when Casp8–/– mice were crossed with Rip3–/–, the DKO mice developed normally with no stem cell defect. We hypothesize that these pathways exist as biological constraints on epigenetic plasticity and that pharmacological or genetic ablation could enhance EC reprogramming. To test our hypothesis, we transdifferentiated WT and Casp8–/–Rip3–/– DKO MEFs using our protocol, employing an innate immunity modifier and EC growth factors. Our preliminary data showed that DKO MEFs transdifferentiated to induced-EC (iECs) with >10-fold higher yield when compared to WT (yields ~30%). Genetic and functional assays showed that iECs generated from DKO MEFs were comparable to WT, indicating that removal of apoptotic pathways did not lead to aberrant reprogramming. Moreover, pharmacological inhibitors of death receptors when combined with our small molecule cocktail showed a similar increase in iEC generation in human fibroblasts. This study is a first step toward development of a regenerative strategy for PAD on the use of ECs derived from small molecules and growth factors without use of viral vectors encoding TFs.
Basic Science – Other Poster 3
The Effect of Ultra High Levels of C-Reactive Protein (CRP) on the Coagulation System
Ramin Artang1, Daniel Anderson1, Jorn Dalsgaard Nielsen2
1University of Nebraska Medical Center, Omaha, NE, USA; 2Copenhagen University Hospital, Bispebjerg, Denmark
Background: There has been conflicting evidence about the role of CRP in atherothrombosis as active mediator or innocent bystander in subjects with ischemic heart disease, stroke and peripheral arterial disease. Activation of inflammation and coagulations markers was previously demonstrated at intermediate levels of in vivo concentrations of Recombinant Human (rh) CRP. The purpose of this study was to evaluate the effect of ultra high physiologic levels of purified human (ph) CRP on coagulation system.
Methods: PhCRP concentrate (300 micro liter) synthesized from human pleural fluid was added to citrated whole blood collected from 5 healthy volunteers at escalating concentrations of 0, 10, 120, 250 ng/L and was incubated for 30 minutes on a test tube rocker. Coagulation parameters including PT, PTT, D-dimer and maximum amplitude by thrombelastography were measured and compared to baseline values using ANOVA test.
Results: There was no significant change noted on any of the parameters with escalating dose CRP (Figure).
Conclusion: CRP has no direct effect on the coagulation system in an isolated whole blood ex vivo coagulation model without contribution from the endothelial cells. The prothrombotic effect of CRP observed in previous studies may be attributed to the contribution of the endothelial cells and furthermore likely by acute phase response due to contaminant bacterial products present in the production of bacterial based rhCRP used in contrast to the phCRP used in present study.
Clinical Science/Epidemiology – Arterial and Aortic Disease Poster 4
Risk Factors for Progression of Asymptomatic Carotid Artery Stenosis
Hartaj Girn, Han Tun, Leonardo Clavijo, David Shavelle, Michael Gaglia, Parveen Garg
Keck Medical Center of USC, Los Angeles, CA, USA
Background: A direct relationship exists between carotid artery disease progression and stroke incidence. It is unclear though which individuals are at greater risk for disease progression. We examined clinical characteristics associated with disease progression to a higher level of internal carotid artery (ICA) disease in patients undergoing carotid duplex ultrasound (CDU) surveillance.
Methods: We retrospectively studied 267 patients without severe ICA stenosis at baseline (⩾79%) who underwent CDU from 2008 to 2011 and had at least one subsequent CDU ⩾11 months later. Symptomatic patients (stroke or TIA within 6 months) and carotid arteries with prior intervention were excluded. Baseline demographic and clinical data were recorded. The primary outcome was progression of disease to a higher category of stenosis that was at least ⩾50% (moderate [50–79%], severe [80–99%], or occluded [100%]). Multivariate logistic regression analysis was performed to evaluate for predictors of progression.
Results: Of the 267 patients, 51 demonstrated ICA progression in either or both arteries (19%). Patients with disease progression were older (74 vs 70, p<0.01), more likely to smoke (55% vs 38%, p=0.03), and more likely to have moderate (50–79%) ICA stenosis (55% vs 25%, p<0.01) at baseline compared to those without disease progression (Table). There were no other significant differences in baseline characteristics. In a multivariate logistic regression analysis, only moderate baseline ICA stenosis predicted carotid disease progression (OR: 2.9; 95% CI 1.4–6.3).
Conclusion: Carotid disease progression was common in our study population. Other than moderate ICA stenosis, we did not identify any additional baseline characteristics associated with carotid disease progression. Our results support current recommendations for routine duplex surveillance in asymptomatic individuals with baseline ICA stenosis >50%.
Baseline characteristics.
Clinical Science/Epidemiology – Arterial and Aortic Disease Poster 5
Vascular Endothelin-1 Activity is Not Associated with Age in Patients with Type 2 Diabetes Mellitus
Andrew E Berdy1, Vijaywant Brar2, Julio A Panza3, Umberto Campia4
1MedStar Georgetown University Hospital, Washington, DC, USA; 2MedStar Washington Hospital Center, Washington, DC, USA; 3Westchester Medical Center, Valhalla, NY, USA; 4MedStar Heart and Vascular Institute, Washington, DC, USA
Background: Vascular endothelin-1 (ET-1) activity is elevated in patients with Type II Diabetes Mellitus (DM-II) and increases with age in healthy men. However, the effect of increasing age on ET-1 activity in diabetic patients is unknown. This study investigated the hypothesis that age is directly associated with ET-1 activity in patients with DM-II.
Methods: Retrospective analysis of ET-1 activity data collected in diabetic patients. Endothelin-1 activity was expressed as forearm blood flow (FBF) responses by strain-gauge plethysmography during the intra-arterial infusion of the selective endothelin type-A receptor antagonist BQ-123 (100 nmol/min) for 60 minutes. Changes in FBF from baseline in response to BQ-123 were assessed by one-way ANOVA for repeated measures. Association analyses were performed with use of the Pearson correlation coefficient.
Results: Data from 34 patients were included in the current analyses. The baseline characteristics of the study population are reported in the Table. Infusion of BQ-123 induced a significant increase in FBF from baseline (p<0.001). The percent increase in FBF from baseline at 60 minutes of BQ-123 infusion was not significantly associated with age (r=0.143; p=0.436), nor with blood pressure or with markers of endothelial activation (p=NS for all).
Conclusions: In patients with DM-II, vascular ET-1 activity is not significantly associated with age. Our findings suggest that, in diabetic patients, the mechanisms underlying increased vascular ET-1 activity are independent of the effects of increased age on the vasculature.
Characteristics of the patient population.
Clinical Science/Epidemiology – Arterial and Aortic Disease Poster 6
Effects of Race on Adhesion Molecules and Adipokines Levels in Patients with Cardiovascular Risk Factors
Vijaywant Brar1, Andrew E Berdy2, Julio A Panza3, Umberto Campia1
1MedStar Washington Hospital Center, Washington, DC, USA; 2MedStar Georgetown University Hospital, Washington, DC, USA; 3Westchester Medical Center, Valhalla, NY, USA
Background: Circulating cell adhesion molecules are markers of endothelial activation that participate in vascular inflammation. Adipokines are adipocyte-derived hormones with multiple vascular actions, which may modulate the development of atherosclerosis. Whether race-specific differences exist in adhesion molecules and adipokines levels has not been investigated. We tested the hypothesis that the expression of adhesion molecules and adipokines differs between African American (AA) and Caucasian Americans (CA) patients with cardiovascular risk factors (CRFs).
Methods: Retrospective analysis of data collected in a study that investigated vascular function in patients with CRFs. Plasma levels of adhesion molecules and adipocytokines were measured with commercially available ELISA and radioimmunoassay kits.
Results: Data from 75 patients were included in the present analyses. Their baseline characteristics are reported in the Table. The levels of ICAM and VCAM were significantly higher in CA than AA (p = 0.03 and 0.01, respectively). No significant differences were observed in adipokine levels between the two groups. On multivariable analysis, ICAM levels could not be predicted by age, total cholesterol, LDL, HDL and triglycerides; however, age was a significant predictor of VCAM levels.
Conclusions: Levels of the adhesion molecules ICAM and VCAM are higher in CA than in AA; however, the difference in VCAM may be related to older age in CA. No differences in adipokines levels appear to be present between AA and CA. Further study is necessary to confirm our findings in larger populations and to investigate the clinical relevance of these findings.
Baseline characteristics of study participants.
Clinical Science/Epidemiology – Arterial and Aortic Disease Poster 7
Evidence of Systemic Atherosclerosis in Young Adults with Acute Myocardial Infarction
Tasneem Z Naqvi1, Kimberly Atianzar2, Ruzaik Ibrahim2, Thiri Oo2
1Mayo Clinic, Scottsdale, AZ, USA; 2University of Southern California, Los Angeles, CA, USA
Background: B-mode ultrasound (US) of carotid intima media thickness (CIMT) is recommended by ASE to detect subclinical atherosclerosis in patients with intermediate Framingham Risk Score (FRS) and not recommended by recent ACC/AHA prevention guidelines. Majority of patients with acute myocardial infarction (AMI) have low or intermediate FRS. We evaluated the ability of CIMT and plaque in identifying systemic atherosclerosis in low FRS patients presenting with AMI.
Methods: Two trained scanners performed bilateral CIMT assessment in 25 in-patients <55 yrs old without diabetes or smoking history who presented with first AMI and 25 matched in-patients admitted for non-cardiac reasons. Plaque was defined as >1.5 mm focal protrusion and was assessed in short axis sweep and 3 long axis views. Far wall common carotid artery mean and max IMT were measured bilaterally at 3 angles using ASE protocol and a Philips IE 33 ultrasound system equipped with a 7–13 MHz linear transducer. Off line measurement of IMT was performed using AMS software (Sweden).
Results: Baseline characteristics of the two groups are shown in the Table. Both groups had similar low FRS (5.3±2.3 vs 4.3±2.9, p=0.2). There were 56% Hispanics, 12% African American, 16% Asian and 16% Caucasian. 24% were women and 32% had history of hypertension. AMI patients were more likely to have plaque vs controls (OR 3.78; 95% CI, 1.17–12.19). Patients had significant increase in IMT compared to controls (Figure). Correlation coefficient b/w blinded measurements by 2 scanners for mean CIMT and mean max CIMT in 118 images was 0.99.
Conclusion: Our study suggests that increased CIMT and plaque is present in subjects at low FRS who present with AMI, indicating a role of CIMT and plaque assessment in assessing atherosclerosis in subjects with low FRS.
Clinical Science/Epidemiology – Arterial and Aortic Disease Poster 8
Lower Ankle–Brachial Index within the Normal Range is Associated with Delayed Post-Exercise Phosphocreatine Recovery of the Thigh Muscles
Majd AlGhatrif1, Seongjin Choi2, Kenneth Fishbein2, Eleanor Simonsick2, Matt Oberdier2, Elizabeth Ratchford3, Maya Salameh3, Rajiv Thakkar3, Stephanie Studenski2, Richard Spencer2, David Reiter2, Luigi Ferrucci2
1Johns Hopkins School of Medicine/National Institute on Aging, Baltimore, MD, USA; 2National Institute on Aging, Baltimore, MD, USA; 3Johns Hopkins School of Medicine, Baltimore, MD, USA
Reduced lower extremity perfusion in peripheral artery disease (PAD), manifested by Ankle–Brachial Index (ABI) of less than 0.9, is associated with impaired muscle mitochondrial energy production. This is attributed to inadequate oxygen delivery and/or intrinsic mitochondria dysfunction due to repeated episodes of ischemia-reperfusion injury. Whether lower ABI within the normal range reflects a subclinical reduction in lower extremity perfusion that impairs mitochondria energy production is not clear. We examined the association between ABI and thigh muscle post-exercise phosphocreatine recovery time constant (τPCr), a measurement of mitochondrial energy production, in 48 men and 66 women free of clinical PAD participating in the Baltimore Longitudinal Study of Aging. Left thigh post-exercise τPCr was measured by phosphorus magnetic resonance spectroscopy (31P-MRS) of the left vastus lateralis muscle performed on a Philips 3T Achieva platform after a series of ballistic knee extensions. Left ABI was measured by the Colin system. The sample mean age was 71±12 years; ABI values ranged between 0.92 and 1.4 (1.16±0.09). None of the participants had diabetes; 4% were current and 40% were former smokers. τPCr values ranged between 21.6 and 70.8 sec (43.5±10.8). There was significant associations of τPCr with ABI (β = −0.27, p=0.0171) (Figure) and age (β=0.26, p=0.0017). The association between ABI and τPCr remained significant after adjusting for age and smoking status (β = −0.21, p=0.0282). In conclusion, lower ABI within the normal range was associated with impaired muscle energetics assessed by τPCr. Thus, lower ABI even within the normal range could represent a subclinical reduction in lower extremity perfusion, which negatively affects muscle energy production. Future prospective studies are needed to examine this association and investigate the long terms effects of such hypoperfusion.
Univariate linear regression analysis showing delayed post-exercise thigh muscle phosphocreatine recovery time constant (τPCr) with reduced ankle-brachial index.
Clinical Science/Epidemiology – Arterial and Aortic Disease Poster 9
Presence of Congestive Heart Failure Does Not Predict Significant Carotid Atherosclerosis in Absence of Traditional Risk Factors
Olusegun Osinbowale, Sayf Al-tabaqchali, Alexandre Benjo
Ochsner Clinic, New Orleans, LA, USA
Background: Atherosclerosis is a diffuse systemic process that can affect multiple vascular beds including the coronary, carotid and lower extremity arteries. The risk factors for this disease seem to be common to all vascular territories with some variation of the degree of importance. As with atherosclerosis, the prevalence of congestive heart failure (CHF) has risen though the degree of association is not widely reported. We undertook a retrospective evaluation of carotid artery stenosis (CAS) in subjects with CHF compared to traditional atherosclerosis risk factors.
Methods: From January to November 2014 we performed 2118 carotid duplex scans in patients without prior local interventions. We aimed to define predictors of severe carotid stenosis defined as >70%. All studies were reported by a single interpreter using internally validated criteria. We evaluated the presence of traditional cardiovascular risk factors such as smoking, hypertension, diabetes, known coronary or peripheral arterial disease (CAD or PAD), chronic kidney disease (CKD) and age as well as that of systolic or diastolic heart failure in univariate analysis. We used correlating diagnosis codes in the electronic record to identify the clinical variables.
Results: Data analysis revealed that prior CAD or PAD, CKD, advanced age and Caucasian race were significantly associated with presence of severe asymptomatic CAS. PAD represented the strongest risk factor with p<0.0001; followed by CAD (p<0.0048). CHF and presence of diabetes mellitus did not exhibit statistical significance.
Conclusions: Congestive heart failure without other traditional risk factors may fail to predict the presence of severe CAS. Due to the sample size and retrospective study nature it remains to be determined whether carotid screening may benefit subgroups of CHF patients such as those with ischemic vs nonischemic cardiomyopathy.
Clinical Science/Epidemiology – Arterial and Aortic Disease Poster 10
Impact of Cognitive Function on Exercise Performance and Quality of Life in Patients with Symptomatic Peripheral Artery Disease
Polly Montgomery1, Daniel Zhao1, Shari Waldstein2, Andrew Gardner1
1Univiversity of Oklahoma HSC, Oklahoma City, OK, USA; 2Univiversity of Maryland Baltimore County, Baltimore, MD, USA
Purpose: To determine whether cognitive function was associated with the primary outcome measure of peak walking time (PWT), and with secondary outcome measures related to mobility, community-based ambulation, health-related quality of life (QoL), and vascular function in patients with claudication and PAD.
Methods: Cognitive function of 246 patients was assessed with the mini-mental state examination (MMSE) questionnaire. Patients were grouped according to whether they had a perfect MMSE score of 30 points (n=123) or whether they missed one or more points (n=123). Patients were characterized on numerous functional and vascular outcomes, among which included PWT during a graded maximal treadmill test and QoL.
Results: Compared to the Higher MMSE group, there was a trend for lower PWT in the Lower MMSE group (p=0.055) after adjusting for age, sex, race, and education level (model 1), which became significant (375±245 s vs 456±271 s, p=0.045) after adjusting for variables in model 1 plus coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), and arthritis (model 2). Multiple domains of QoL were lower (p<0.05) in the Lower MMSE group after adjusting for model 1, but only mental health remained lower (75±20% vs 80±5%, p=0.019) after further adjustment with model 2.
Conclusion: In symptomatic patients with PAD, lower cognitive function was associated with greater ambulatory impairment than in patients with higher cognitive function. Furthermore, lower cognitive function was associated with impairment in multiple domains of health-related QoL, all of which except mental health were explained by the comorbid conditions of CAD, COPD, and arthritis.
Clinical Science/Epidemiology – Arterial and Aortic Disease Poster 11
Lower Ankle–Brachial Index within the Normal Range is Associated with Accelerated Decline in Thigh Muscle Strength and Quality: Results from the Baltimore Longitudinal Study of Aging
Majd AlGhatrif1, Ellisa Fabbri2, Ann Zenobia Moore2, Matt Oberdier2, Rajiv Thakkar3, Elizabeth Ratchford3, Maya Salameh3, Eleanor Simonsick2, Stephanie Studneski2, Luigi Ferrucci2
1Johns Hopkins School of Medicine, National Institute on Aging, Baltimore, MD, USA; 2National Institute on Aging, Baltimore, MD, USA; 3Johns Hopkins School of Medicine, Baltimore, MD, USA
Peripheral arterial disease (PAD) and the associated hypoperfusion, manifested by low ankle–brachial index (ABI), result in reduced leg muscle performance. Whether lower ABI within the normal range is associated with alterations in leg muscle properties is unknown. We examined whether lower ABI within the normal range is associated with a future decline in thigh muscle mass, strength and biomechanical quality (strength/mass) in a longitudinal sample of community-dwelling men and women free of clinical PAD. Study sample included 214 men and 197 women from the Baltimore Longitudinal Study of Aging with a mean follow-up of 4 years (1–8 years) and 2–7 follow-up visits. Thigh muscle area was assessed by CT and knee-extensor strength at 30 degrees was assessed by isokinetic dynamometry; biomechanical muscle quality was calculated as strength/area. ABI was measured using a Colin system. Multivariate linear mixed-effects models adjusting for sex, smoking status, diabetes, and mean blood pressure were used for the longitudinal analyses. Study sample had a mean baseline age of 68.9 ± 10.8 years and ABI of 1.18 ± 0.08. About 4% of the sample had diabetes; current and former smoking rates were 5% and 40%, respectively. There was no association between ABI and thigh muscle area; however, reduced ABI was independently associated with an accelerated future decline in muscle strength and biomechanical quality (Figure). These results suggest that reduced ABI even within the normal range represent a subclinical impairment of lower extremity perfusion, which impacts muscle health and ability to generate force.
Results of linear mixed-effects regression model with and the predicted longitudinal trajectories in muscle quality ratio; there is a steeper decline in muscle quality in those with a baseline ABI of 1.1 vs. 1.3.
Clinical Science/Epidemiology – Arterial and Aortic Disease Poster 12
Prediction of Major Vascular Events in Adult Filipinos with Endocarditis Using the Embolic Risk French Calculator
Jaime M Aherrera, Teresa Abola, Jerelyn Adviento, Maria Margarita Balabagno, Lauro Abrahan, Antonio Faltado, Paul Reganit, Felix Eduardo Punzalan
Philippine General Hospital, Muntinlupa Metro Manila, Philippines
Background: Vascular events, well-established complications of infective endocarditis (IE), have been underreported in local retrospective studies. The embolic risk calculator utilizes several variables to estimate the embolic risk in IE after the initiation of therapy. We aim to determine the efficacy of this embolic risk French calculator in predicting major embolic events. We will also describe the vascular events associated with the disease.
Methods: This is a prospective study done at the Philippine General Hospital. All patients with definite IE were included. The risk of the patients was computed on admission using the embolic risk French calculator. Variables required included age, diabetes, atrial fibrillation, prior embolism prior to antibiotic therapy, vegetation length, and Staphylococcus aureus on blood culture. These patients were followed up for 1 month to determine the incidence of symptomatic embolic events.
Results: 62 patients with a mean age of 41 years were included. 59% presented with vascular phenomenon including: subconjunctival hemorrhage (44%), Janeway lesions (27%), splinter hemorrhages (10%), Roth spots (15%), and embolism prior to antibiotic therapy (15%). Major embolic events developed in 17 patients (27%), the majority of which occurred during the first week of antibiotic therapy. Multivariate analysis identified two variables to be significant predictors of embolic events: a high computed risk using the calculator and an occurrence of an embolism prior to antibiotic therapy. The odds of having an embolic event in those with a high computed risk is 5.47 times higher than those with a low score (OR 5.47, p<0.02).
Conclusion: Major and minor vascular manifestations in endocarditis were more prevalent compared to past studies. This calculator is a useful tool to estimate the risk for embolic events in IE. The risk of developing embolic events should be weighed against the risks of early cardiac surgery during the active phase of IE, as to institute timely and appropriate management.
Clinical Science/Epidemiology – Arterial and Aortic Disease Poster 13
Characterizing Cervical Artery Dissection among Patients with Fibromuscular Dysplasia and the Risk of Symptomatic Dissection Recurrence
Sarah O’Connor, Heather Gornik, Corey Brier, Ellen Brinza, Toni Morris, Esther SH Kim
Cleveland Clinic, Cleveland, OH, USA
Background: Fibromuscular Dysplasia (FMD) is an uncommon non-atherosclerotic disease of medium sized arteries associated with increased risk of cervical artery dissections and stroke in the young. The risk of recurrent dissection is unknown.
Methods: Prevalence and symptoms of cervical artery dissection at the time of initial event and in follow up are reported for patients with FMD at a single center. Rate of recurrent dissection is reported.
Results: Among 382 patients enrolled in the US Registry for FMD at a single center, 80 patients (20.9%) were reported to have had at least one cervical artery dissection. Mean age at dissection was 45.6±8.6 years (range 25–67), and 92.5% were female. 93 discrete dissection events were observed; 17 (18.3%) dissection events involved >1 cervical artery. 19 dissection events (20.4%) were found incidentally. The most common symptoms at the time of dissection were headache (62/69; 89.9%), neck pain (41/64; 64.1%), pulsatile tinnitus (26/64; 40.6%), and Horner’s syndrome (24/60; 40.0%). 37/71 patients (52.1%) presented with a neurologic deficit, 17/70 (24.3%) suffered a stroke. During a median follow up of 36 months (IQR 14.25–66.75, range 2–228 months), 13 patients had a second cervical artery dissection (16.3%), 3 dissections occurred within 6 weeks of the first dissection, 4 recurrent dissections were incidental findings.
Conclusions: FMD is associated with a high prevalence of cervical artery dissection. The recurrence rate was 16.3% at 36 months, with 3.8% occurring within the first 6 weeks of the first dissection.
Clinical Science/Epidemiology – Arterial and Aortic Disease Poster 14
Prevalence of Fibromuscular Dysplasia in Survivors of Spontaneous Coronary Artery Dissection
Alex M Parker, Robert Battle, Amy Tucker, Kanwar Singh, Michael Ragosta, Angela Taylor, Lewis Lipson, John Angle, Alan Matsumoto, Aditya M Sharma
University of Virginia, Charlottesville, VA, USA
Background: Spontaneous coronary artery dissection (SCAD) is an uncommon cause for acute coronary syndromes (ACS). Until recently etiology of SCAD has been unclear however data now suggests correlation between fibromuscular dysplasia (FMD) and SCAD. We sought to identify if a similar correlation existed in our patient population.
Methods: Retrospective chart review on SCAD survivors in the past 5 years at our institution was performed including collecting clinical data, coronary angiogram details, computed tomography angiography (CTA) or magnetic resonance angiography (MRA) of the head, neck, abdomen and pelvis.
Results: Of the 28 patients (pts) with SCAD, all of them were women and mean age was 47.4 years at the time of diagnosis of SCAD. 4 had multi-vessel involvement with left anterior descending artery (59%) being most commonly involved. 29.2% presented with ST elevation ACS. Of the 28 pts, 14 underwent screening for FMD (7 had complete screening from neck to pelvis). 6 of 14 (42.8%) were found to have FMD, and 4 of 7 (57.1%) of those who have completed screening had FMD. FMD was found at 4, 4, 2 and 1 renal, carotid, vertebral and external iliac vascular beds respectively. 4 of 6 (66%) have FMD in more than one vascular bed. 17.8% of all SCAD cases occurred in peripartum period and 1 has concomitant FMD.
Conclusions: Our population had a high prevalence of FMD in SCAD survivors that had screening for FMD. Given the high prevalence of FMD in this patient population, all pts with SCAD should undergo screening for FMD from head to pelvis with either MRA or CTA.
Clinical Science/Epidemiology – Arterial and Aortic Disease Poster 15
Vorapaxar in Patients with Peripheral Artery Disease
Marc P Bonaca, Mark A Creager, Benjamin S Scirica, Sabina A Murphy, Eugene Braunwald, David A Morrow
Brigham and Women’s Hospital, Boston, MA, USA
Background: Vorapaxar inhibits protease-activated receptor 1 expressed on platelets and vascular endothelium and reduces ischemic events in patients with atherosclerotic vascular disease. We investigated the effect of vorapaxar on cardiovascular and limb vascular events in patients with peripheral artery disease (PAD).
Methods: TRA 2°P-TIMI 50 was a multinational, randomized, double-blind, placebo controlled trial of vorapaxar in stable patients with atherosclerotic vascular disease. We evaluated the efficacy and safety of vorapaxar in trial participants with PAD, either established or previously unknown but detected by an abnormal ankle–brachial index (ABI ⩽ 0.90) at baseline. We excluded PAD patients with a history of stroke or TIA.
Results: 6136 patients were randomized and approximately half (3273, 53%) had no history of recent myocardial infarction (within 12 months). Over three years, vorapaxar reduced the rate of CV death (CVD), MI, or stroke (10.7% vs 12.5%, HR 0.85, 95% CI 0.73–0.99, p=0.034) with consistent trends in all components of the primary endpoint (Figure). Vorapaxar also reduced limb vascular events including acute limb ischemia (1.5% vs 2.6%, HR 0.57, 95% CI 0.39–0.84, p=0.005) as well as elective peripheral revascularization (10.8% vs 13.8%, HR 0.80, 95% CI 0.69–0.93). Vorapaxar increased GUSTO moderate or severe bleeding (HR 1.47, 95% CI 1.14–1.89, p=0.003) with similar rates of GUSTO severe bleeding in both groups (1.9% vorapaxar vs 1.7% placebo, HR 1.10, 95% CI 0.72–1.69, p=0.65).
Conclusions: Vorapaxar reduces vascular ischemic events including both major adverse cardiovascular events as well as limb vascular events in a broad population of patients with PAD.
Clinical Science/Epidemiology – Arterial and Aortic Disease Poster 16
Vorapaxar in Patients with Peripheral Artery Disease with or without Previous Limb Revascularization
Marc P Bonaca, Mark A Creager, Benjamin S Scirica, Sabina A Murphy, Eugene Braunwald, David A Morrow
Brigham and Women’s Hospital, Boston, MA, USA
Background: Vorapaxar inhibits PAR 1 on platelets and vascular endothelium and reduces limb vascular events (LVE) in patients with peripheral artery disease (PAD). We examined whether the effect of vorapaxar on LVE was different in patients with and without a history of peripheral revascularization or amputation (prior limb procedure).
Methods: TRA 2°P-TIMI 50 was a multinational, randomized, double-blind, placebo controlled trial of vorapaxar in stable patients with atherosclerotic vascular disease. We evaluated the effect of vorapaxar on LVE in patients with symptomatic PAD and no history of stroke/TIA and stratified by history of prior limb procedure.
Results: There were 3273 patients who qualified for the study because of symptomatic PAD, and 2089 (64%) of these had history of prior limb procedure. Overall vorapaxar reduced acute limb ischemia (HR 0.56, 95% CI 0.37–0.84, p=0.005) and peripheral revascularization (HR 0.83, 95% CI 0.71–0.97, p=0.023). Patients with prior limb procedure had higher rates of acute limb ischemia (placebo group; ALI, 5.5% vs 1.8% placebo group) and peripheral revascularization (25.6% vs 14.9% placebo group) compared to patients with no history of limb procedure (Figure). The effect of vorapaxar on LVE was consistent in both groups (p-interaction NS or both endpoints; Figure). Vorapaxar increased GUSTO moderate or severe bleeding (overall HR 1.58, 95% CI 1.15–2.19) consistently in both group (p-interaction 0.81).
Conclusions: Patients with symptomatic PAD and history of limb procedures have higher rates of LVE compared to patients with no history of limb procedures with a 3-fold risk for ALI. Vorapaxar reduced limb vascular events in patients with and without prior limb procedures.
Clinical Science/Epidemiology – Arterial and Aortic Disease Poster 17
A Correlation Study of the Diameter of Common Femoral, Radial and Abdominal Arteries with Age, Gender and Anthropometrics Among Filipino Adults in a Private Training Hospital
Beinjerinck Ivan Cudal, Jasmin Melissa Bernardo, Blaise Liao
Makati Medical Center, Makati, Philippines
Clinical Research in Vascular Medicine Data has been published on the baseline artery size of the abdominal aorta, common femoral and radial arteries among Caucasians and Asians to determine the suitability of performing cardiac diagnostic and therapeutic interventions, however minimal studies have been conducted in Philippine setting. This study aims to compile and generate a baseline data on the diameter of the radial, common femoral and abdominal arteries and determine the correlation with weight, height, body surface area and body mass index between Filipinos. This study is a prospective, correlation study on the said arteries using two-dimensional ultrasound and Doppler examination in 35 Filipino participants between September to October 2014 who consulted at the Makati Medical Center Executive Health Unit and that of healthy Filipino volunteers. Individuals having known uncontrolled hypertension with blood pressure, obesity with BMI > 40, smoking history more than ten pack-years, those with aneurysm, and those with end stage renal disease on hemodialysis were excluded. The mean diameter of radial artery diameter in our study was 0.22cm ± 0.04cm and common femoral artery is 0.74cm ± 0.10cm which are close to observational values of other studies done previously. Abdominal aorta was 1.34–0.18cm at the level of superior mesenteric artery and 1.18–0.14cm at the level of prior to bifurcation as common iliac arteries are noted to be slightly smaller compared to earlier analyses. The measured diameters of radial, common femoral and abdominal arteries were directly correlated to weight, height, body surface area, and body mass index. Women were noted to have smaller arterial diameter compared to men. Age was the only factor that directly correlated with of the abdominal aorta diameter.
Clinical Science/Epidemiology – Arterial and Aortic Disease Poster 39
An Extremely Rare Case of Primary Aorto-Duodenal Fistula in a Filipino Patient
John Daniel Ramos, Patrick Maglaya, Maria Teresa Abola
UP-Philippine General Hospital, Manila, Philippines
Primary aorto-duodenal fistula (PADF) is a communication between the duodenum and the aorta without history of abdominal aortic aneurysm repair. This is a very rare lesion. A 62 year old Filipino male, with no history of previous surgery, consulted at the ED for hematemesis, melena, dizziness, and generalized weakness. He was pale and weak-looking, blood pressure was 80/50 mmHg, and cardiac rate was 94 bpm. Abdominal exam was unremarkable. Rest of PE was normal. A repeat EGD with endoscopic ultrasound revealed a 6 × 6 hypoechoic lesion on color flow Doppler, extrinsically compressing the area between the second and third parts of the duodenum. This lesion had a central umbilication, with note of actively oozing blood. Contrast abdominal CT scan revealed an infrarenal abdominal aortic aneurysm, measuring 7.6cm × 5.9cm × 7.0cm. The aneurysm was related to the third segment of the duodenum with an outpouching that bored into the duodenal wall. No frank contrast extravasation to the duodenum was seen. Patient underwent exploratory laparotomy which revealed the primary aortoduodenal fistula at the anterolateral aspect of the fourth segment of the duodenum. He had a stormy hospital course when he contracted peritonitis from a duodenal dehiscence. He succumbed to pneumonia on his 19th postoperative day. To our knowledge, this is the first case reported in our institution. The high mortality of PADF is attributed to challenges in diagnosis. A high index of suspicion is needed. The dictum is that gastrointestinal bleeding, combined with a negative endoscopy in the presence of an aneurysmal aorta, suggests PADF and requires urgent CT evaluation. Surgery is the only chance for survival among patients.
Clinical Science/Epidemiology – Arterial and Aortic Disease Poster 41
Bilateral Renal Artery Stenosis in a Young Filipino Male with Takayasu’s Arteritis
Abrahan LL IV, Abola MTB
University of the Philippines-Philippine General Hospital, Manila, Philippines
Background: In the West, 90% of renal artery stenosis (RAS) is atherosclerotic and 10% secondary to fibromuscular dysplasia (FMD). However, an important differential in the young Asian population is Takayasu’s arteritis (TA). We present a unique case of a Filipino male diagnosed with bilateral RAS secondary to TA despite the lack of systemic/inflammatory signs and symptoms.
Case summary: A 29-year-old Filipino presented with a 2-year history of hypertension, with BP ranging from 140–160/80–90. He reported nape pains and occipital headaches, but no constitutional symptoms, joint pains or arm/leg claudication. Physical examination was normal except for periumbilical bruits and a weak right dorsalis pedis pulse. CBC, creatinine, electrolytes, thyroid function, urinalysis, and ESR and CRP were all normal. Left ventricular hypertrophy was noted on ECG and 2D echocardiography. A magnetic resonance angiogram revealed high-grade stenosis at the ostia of bilateral renal arteries. There were two areas of aneurysmal dilatation involving the suprarenal abdominal aorta. Adrenals were normal. The initial consideration was FMD, but the lesions’ ostial location and aortic dilatation raised our index of suspicion for Takayasu’s arteritis. A subsequent CT aortogram clinched the diagnosis, demonstrating significant stenosis in the celiac trunk, superior mesenteric artery and bilateral renal arteries, as well as diffuse dilatation of the inferior mesenteric artery. His blood pressure is currently controlled on amlodipine and carvedilol. Steroids are reserved for flares of activity.
Conclusion: In a young patient with RAS, ostial lesions always warrant further investigation for Takayasu’s arteritis even with a paucity of clinical symptoms.
Clinical Science/Epidemiology – Clinical Trials Poster 18
Recruitment of African Americans into a Walking Intervention Trial for Peripheral Artery Disease
Brittany Love, Daniel Nwachokor, Tracie C Collins
University of Kansas School of Medicine, Wichita, KS, USA
Background: Recruitment for clinical trials of patients with peripheral artery disease (PAD) can be challenging. We explored effective recruitment strategies for an NIH funded clinical trial which focuses on African Americans with PAD.
Methods: We present recruitment strategies over an 18-month time-frame for a 12-month randomized clinical trial, conducted in Wichita, KS, to determine the efficacy of motivational interviewing to promote walking in African Americans with PAD. Study participants had to meet the following criteria: (1) African American, (2) resting ankle–brachial index (ABI) ⩽ 0.95, (3) English speaking, and (4) telephone access. Ten different recruitment methods were used and interested participants contacted us to undergo telephone screening. Using descriptive statistics, we captured the number of African Americans telephone screened and the number randomized.
Results: Direct mailings provided the greatest yield for recruitment. Among 822 Africans Americans who were telephone screened, nearly 10% (n=82) were randomized into our trial (Table).
Conclusion: The most successful recruitment strategies for a randomized clinical trial involving African Americans with PAD were mailings, word of mouth, and fliers. Recruitment within future trials of racially diverse populations with PAD should consider these approaches to achieve successful enrollment.
Recruitment Strategies and Number of Participants Randomized.
Clinical Science/Epidemiology – Clinical Trials Poster 19
Influence of Diabetes on Ambulation and Inflammation in Men and Women with Symptomatic Peripheral Artery Disease
Andrew W Gardner1, Donald E Parker1, Polly S Montgomery1, Danuta Sosnowska1, Ana I Casanegra1, Zoltan Ungvari1, Anna Csiszar1, Sarah X Zhang2, Josh J Wang2, William E Sonntag1
1University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; 2University of Buffalo, Buffalo, NY, USA
Purpose: To determine whether diabetes and sex were factors associated with gait speed, ambulatory function, endothelial cell inflammation, oxidative stress, and apoptosis, and with circulating biomarkers of inflammation and antioxidant capacity in patients with peripheral artery disease (PAD) and claudication.
Methods: Ambulatory function of 180 symptomatic men and women with PAD was assessed during a graded maximal treadmill test, a 6-minute walk test, and a 4-meter walk test. Patients were further characterized on the endothelial effects of circulating factors present in the sera using a cell culture-based bioassay on primary human arterial endothelial cells, and on circulating inflammatory and vascular biomarkers.
Results: Men with diabetes had a lower 6-minute walk distance by a mean of 62 meters compared to men without diabetes (p<0.01), and the diabetic men had a slower gait speed over four meters (p<0.05). In contrast, no significant differences (p>0.05) in 6-minute walk distance and gait speed were found in women with and without diabetes. Although both men and women with diabetes had higher pigment epithelium derived factor (p<0.05) and leptin values (p<0.05) than those without diabetes, only the women with diabetes had elevated high sensitivity C-reactive protein (HsCRP) (p<0.01), E-selectin (p<0.05), and interleukin-6 (p<0.05) than women without diabetes. These differences were not observed between diabetic and non-diabetic men.
Conclusions: In patients with PAD, the negative health consequences associated with diabetes are sex dependent. Compared to patients free of diabetes, men with diabetes have impaired ambulation, whereas women with diabetes have impaired inflammation. The clinical implication is that medical management of diabetes may improve men and women with PAD differently, as men may improve their ambulation while women may lower their inflammation and vascular risk.
Clinical Science/Epidemiology – Clinical Trials Poster 20
Design of the OMEGA-PAD II Trial: The Effects of Omega-3 Fatty Acids on Peripheral Arterial Disease II
Marlene Grenon, Michael Conte, Hugh Alley, Christine Patton, Warren Gasper, Christopher Owens
UCSF, San Francisco, CA, USA
Introduction: Despite current available medical and surgical therapies, patients with peripheral artery disease (PAD) continue to be at an unacceptably high risk for morbidity including limb loss and death. The OMEGA-PAD I trial (NCT01310270), a randomized, double-blinded, placebo-controlled trial, demonstrated that short duration, high-dose n-3 polyunsaturated fatty acids (n-3 PUFA) oral supplementation increases the production of downstream n-3 PUFA derived products and mediators in patients with PAD. The OMEGA-PAD II study will examine the hypothesis that high-dose n-3 PUFA oral supplementation improves systemic inflammation, vascular function, and symptomatic status of patients with PAD.
Methods: The OMEGA-PAD II study (NCT01979874) is a double-blinded, randomized, placebo-controlled trial that will enroll 70 patients aged ⩾ 50 with mild-severe claudication receiving 4.4 g/day of n-3 PUFA orally for 3 months vs placebo. The primary endpoint will be improvement in systemic inflammation, and the secondary endpoints will include endothelial function using brachial artery flow-mediated vasodilation (FMD), walking performance with a 6-min walking test, n-3 PUFA metabolome changes, lipid profile and walking impairment questionnaires.
Results: Ten patients (all males) have either completed the study or are currently enrolled in the trial. Mean age is 71 ± 8 yo, 60% are Caucasian, 100% are smokers, 80% have hypertension, 80% have hyperlipidemia, 10% are diabetic, 50% have a history of coronary artery disease. Mean C-reactive protein is 2.7 ± 2.7 mg/l and mean FMD is 7.9 ± 3.7%. The trial is currently ongoing.
Conclusions: The OMEGA-PAD II trial will help us further understand the impact of n-3 PUFA supplementation in patients with stable claudication, with the aim to translate these findings in the clinical care of patients with PAD.
Clinical Science/Epidemiology – Endovascular Therapies Poster 21
Endovascular Treatment of May-Thurner Syndrome: Ten Years’ Experience of a Cardiovascular Center in Colombia
Nathalie Hernandez, Juan Gomez, Olga Loterp, Diana Ramirez, Juan Muñoz
Clínica Cardio VID, Medellin, Colombia
Objective: To describe the clinical characteristics, presentation, treatment and follow-up of a group of patients at the Clínica Cardio VID with a diagnosis of May–Thurner syndrome.
Methods: Medical records were reviewed of patients diagnosed with May–Thurner between 2004 and 2014. Variables assessed: age, sex, clinical presentation, previous history of deep vein thrombosis, diagnosis, treatment, outcome and follow-up.
Results: We describe 48 cases, 100% female, aged between 20 and 60 years. Initial presentation: acute venous thrombosis, 90% of patients with ilio femoral segment involvement and 10% of patients with symptoms of venous hypertension (edema, pain and varicose veins). Of the latter group, 1 patient had history of deep vein thrombosis and 2 of infrapopliteal superficial venous thrombosis, and history of varicectomy. Diagnosis was obtained in patients without thrombosis using duplex ultrasound, which evidenced a decrease in vessel diameter greater than 70%, and in all patients with measurement of gradients between the inferior vena cava and left common iliac. 100% of patients with acute thrombosis underwent thrombolysis and stent implantation. Technical success was 100%. Follow-up was by anticoagulation according to protocols. Monitoring was done with color duplex and clinical symptoms were present in 80% of patients for 1 month to 72 months (mean 24 months). Follow-up showed no recurrence of thrombosis or symptoms, and was ranked with a Villalta score = 0. Average length of hospital stay was 5 days.
Clinical Science/Epidemiology – Endovascular Therapies Poster 22
Contemporary Endovascular Management of Aortoiliac Occlusive Disease
Marin Nishimura1, Gagan D Singh2, Ehrin J Armstrong1, Justin Hildebrand1, Bejan Alvandi1, Walid Sharif1, Marcello Chang1, Misty Humphries1, Nasim Hedayati1, John R Laird1
1University of California Davis School of Medicine, Sacramento, CA, USA; 2University of California Davis Medical Center, Sacramento, CA, USA
There are limited data reporting outcomes after contemporary endovascular intervention for aortoiliac occlusion. From 2006 to 2013, 401 patients underwent endovascular procedures to treat aortoiliac disease at our institution. Baseline demographics, lesion/procedural characteristics, and outcomes for treatment of aortoiliac stenosis vs occlusion were reviewed retrospectively and analyzed. Binary restenosis was determined by peak systolic velocity ratio >2.0 by duplex ultrasound on follow-up at 1mo, 3mo, 6mo, and at 1 year. 401 patients underwent 695 endovascular interventions (n=37 distal aorta, n=390 common iliac, n=264 external iliac, n=11 internal iliac). The indication for intervention was claudication in 63% and critical limb ischemia in 37%. Additional baseline demographics and lesion characteristics of the two groups are shown in Table 1. Lesion lengths were 41 ± 23 mm for stenosis and 62 ± 24 mm for occlusion (p=0.00001). There were less TASC C/D patients in the stenosis cohort (29% vs 69%, p=0.0001). There was no significant difference in procedural characteristics (use of balloon angioplasty, cutting balloon angioplasty, stent placement) between the two groups. Lesion success was 99% in the stenosis group vs 93% in the occlusion group (p=0.0001). At 1 yr, primary patency (75% vs 70%), amputation rates (4% vs 0%), overall survival (90% vs 87%), and target lesion revascularization (13% vs 14%) were not statistically different. Contemporary endovascular management of aortoiliac occlusion is associated with high procedural success (93%) and mid-term outcomes that are similar to treatment of stenotic lesions.
Patient demographics.
Clinical Science/Epidemiology – Endovascular Therapies Poster 23
Incidence and Outcomes of Depression in Veteran Patients with Peripheral Artery Disease: Insights from the XLPAD Registry
Atif Mohammad1, Karan Sarode2, Ryan Master2, Bushra Akram3, Shirling Tsai2, Emmanouil S Brilakis2, Subhash Banerjee2
1UT Southwestern Medical Center, Dallas, TX, USA; 2UT Southwestern Medical Center/Dallas VAMC, Dallas, TX, USA; 3VA North Texas HealthCare System, Dallas, TX, USA
Background: Currently, there is limited evidence on the impact of depressive symptoms on disease severity and clinical outcomes of patients with peripheral artery disease (PAD).
Methods: We analyzed consecutive Veteran patients enrolled in the Excellence in Peripheral Artery Disease (XLPAD; NCT01904851) registry undergoing endovascular revascularization of infrainguinal peripheral arteries between July 2005 and September 2014. Depression was recorded based on established clinical diagnosis entered in the electronic medical records.
Results: A total of 340 patients were analyzed; 91 (26.8%) had depression. Those with depression were younger (62.5±7.2 vs 64.9±8.2; p=0.012) and white (74.7% vs 60.6%; p=0.047), without significant gender differences. Smoking, diabetes mellitus and prior coronary artery disease were equally distributed between depressed and non-depressed patients. Patients with depression presented predominantly with claudication over critical limb ischemia (17.8% vs 28.5%; both p=0.041), and predominantly underwent superficial femoral artery revascularization (93.4% vs 79.5%; p=0.023). Lesion length was longer in patients with depression (135.9±84.2 mm vs 121.5±71.2 mm; p=0.164). Overall major adverse cardiovascular events and major adverse limb events at 12 months were similar in depressed and non-depressed patients, except for higher target limb planned or unplanned amputation rates in the later (11.2% vs 4.4%; p=0.040; Figure).
Conclusions: Associated depression is present in nearly 27% of patient with PAD, undergoing endovascular intervention. These patients are younger, predominantly white, and often present with claudication. Overall 12-month clinical outcomes are similar to the non-depressed, except for higher rates of planned or unplanned amputation of target limb in the non-depressed.
Clinical Science/Epidemiology – Endovascular Therapies Poster 40
IVC Filter Complication: A Case Report
Ma. Belen A Balagapo
Philippine Heart Center, Quezon City, Philippines
An inferior vena cava (IVC) filter is a device implanted into the IVC to prevent life-threatening pulmonary embolism (PE) in high-risk patients who cannot be sufficiently anticoagulated. Long-term complications with prolonged filters include migration, embolization, detachment of device components or fracture and perforation. For when the risk of PE is short term, retrievable filters were introduced. Filter removal is recommended if patients are deemed low risk for embolism and have sufficient anticoagulation, except those with recurrent DVT who require a permanent filter for long-term PE protection. Such is the case of E.G., a 50-year-old male, who had IVC filter insertion in 2002 due to a DVT that developed when he suffered intracerebral hemorrhage and was confined for a month. He was well until after he fell from the stairs, sustaining right flank pain and leg edema, and was thus admitted. An abdominal CT showed a 13.9 × 6.4 × 5.1 cm right retroperitoneal mass and displaced right kidney. An exploratory laparotomy was done but was terminated when a huge hematoma was seen. He was transferred to another hospital where an abdominal CT scan showed retroperitoneal density anterolateral to the right psoas, at L3 up to the right pelvis, 18.0 × 8.4 × 4 cm in diameter with 24 to 45 HU attenuation. An IVC filter was at L2–L3 with bilateral iliofemoral and iliocaval DVT. A repeat explor lap with evacuation of the hematoma was done. A Bard Simon Nitinol filter was noted adherent to the IVC wall, its struts protruding out and lying adjacent to the aorta. This was removed and replaced with a J&J Trapease filter endovascularly. After surgery the patient was on warfarin. He improved and became asymptomatic.
Oblique CT image of IVC filter with hematoma.
Clinical Science/Epidemiology – Other Poster 24
Preoperative Risk Assessment May Not Reduce Cardiovascular Events in Vascular Surgery Patients
Jennifer B Cowart1, Aitua Salami2, Jeffrey T Bates1, Panagiotis Kougias1, Addison A Taylor1
1Michael E DeBakey VA Medical Center, Houston, TX, USA; 2Baylor College of Medicine, Houston, TX, USA
Background: It is currently unclear whether a preoperative vascular medicine (VM) clinic, performing risk stratification (RS) in accordance with the 2007 ACC/AHA guidelines, will affect the outcomes of patients undergoing vascular surgery.
Methods: A retrospective cohort study of 2157 patients who underwent major vascular surgical procedures between February 2006 and January 2013 at a single institution was done. Multivariable logistic regression models were fit to identify the association between preoperative risk stratification and a composite outcome of MI or death, at 30 days and 1 year postoperatively, adjusted for significant pre-, intra- and postoperative variables. These included the Revised Cardiac Risk Index (RCRI) score. A p<0.05 was deemed significant.
Results: At 30 days, there were 66 composite events (3%). Any RS, compared to no RS, was not associated with outcomes (OR 1.24, p=0.42). Compared to no RS, RS by cardiology was associated with increased events (OR 3.69, p=0.00), while RS by VM, anesthesiology, or outside the institution was not associated with a difference in outcome. When controlled for patient-specific variables, this association became non-significant. At 1 year, there were 252 events (11.7%). Any RS, compared to no RS, was not associated with outcomes (OR 1.06, p=0.67). Compared to no RS, RS by cardiology was associated with increased events (OR=2.01, p=0.01) and RS outside the institution was associated with a reduction in events (OR=0.28, p=0.01). RS by VM or anesthesiology was not associated with a difference in outcome. When controlled for patient-specific variables, these associations became non-significant.
Conclusion: When controlling for patient-specific variables including RCRI score, pre-operative RS was not predictive of postoperative MI or death at either 30 days or 1 year.
Clinical Science/Epidemiology – Other Poster 25
Automated Carotid Artery Lumen Measurement Utilizing Ultrasound
Aditya M Sharma1, Tadashi Araki2, Asheed Kumar3, Nobutaka Ikeda4, Francesco Lavra5, Jeny Rajan3, Luca Saba5, Andrew Nicolaides6, John Laird7, Shoaib Shafique8, Jasjit S Suri9
1University of Virginia, Charlottesville, VA, USA; 2Toho University Ohashi Medical Center, Tokyo, Japan; 3National Institute of Technology, Karnataka, India; 4National Center for Global Health and Medicine, Tokyo, Japan; 5University of Cagliari, Cagliari, Italy; 6Vascular Screening and Diagnostic Centre, London, United Kingdom; 7UC Davis Vascular Center, Davis, CA, USA; 8CorVasc Vascular Laboratory, Indianapolis, IN, USA; 9AtheroPoint, Roseville, CA, USA
Introduction: Carotid lumen diameter (cLD) is defined utilizing CT, MR angiogram and conventional angiogram; however, these techniques can be invasive, cause radiation and contrast exposure. Ultrasound, although safe and non-invasive, currently provides only a range of degree of stenosis. The manual cLD measurement is subjective and tedious. Further, due to non-uniformity in plaque growth along the carotid artery makes manual tracing more cumbersome. Thus there is a clear need for an automated cLD measurement system which can measure lumen diameter in real time.
Methods: Automated cLD is a two stage process. Stage 1 estimate the automated region of interest where lumen is present using comprehensive spectral analysis. Stage 2 uses pixel classification paradigm combined with tissue morphology to automatically delineate the lumen-intima interfaces (boundaries) for carotid near and far walls. Finally, diameter is measured using distance method and mean estimated.
Results: 202 patients (males: 155 and females: 75) for left and right CCA (404 images) B-mode ultrasound images (Toshiba® Scanner) were retrospectively obtained at Toho University, Japan. Mean age 69 ± 15.9 yrs; mean M/F age: 67/75 yrs, respectively. Mean HbA1c, LDL, HDL and cholesterol of patients were 6.28±1.1 mg/dl, 101.27±31.6 mg/dl, 50.26±14.8 mg/dl and 175.04±38 mg/dl, respectively. Two Neurologists manually traced the cLD. The coefficient of correlation between automated cLD and manual cLD was: 0.91 and 0.91. The mean cLD errors were: 0.30±0.31 mm and 0.29±0.30 mm. Precision of merit for cLD was: 96.83% and 97.66%, respectively. The system takes only a few seconds.
Conclusions: The lumen diameter measurement is accurate, reliable, quick and fully automated.
Clinical Science/Epidemiology – Other Poster 26
Underutilization of High-Intensity Statins Among Patients with Peripheral Artery Disease (PAD)
Thejasvi Thiruvoipati1, Gagan D Singh2, Ezra A Amsterdam2, Marcello Chang2, John R Laird2, Ehrin J Armstrong3
1University of Colorado Medical Center, Denver, CO, USA; 2University of California, Davis Medical Center, Sacramento, CA, USA; 3VA Eastern Colorado Healthcare System, Denver, CO, USA
High-intensity statins are recommended as first-line therapy in patients with PAD. Studies have shown that high-intensity statin therapy is underused in patients after a coronary heart disease (CHD) event. However, the use of high-intensity statin therapy in patients with PAD has not been investigated. All patients with PAD undergoing angiography at University of California (UC), Davis Medical Center from 2006 to 2014 were identified and evaluated for their prescribed statin therapy. High-intensity statins were defined as atorvastatin 40 to 80 mg, rosuvastatin 20 to 40 mg, and simvastatin 80 mg. All other statins were considered low/moderate-intensity statins. Among 1165 patients with PAD, 777 (66%) were prescribed a statin. Of these patients, 215 (28%) were prescribed a high-intensity statin: 16.6% filled atorvastatin 40 or 80 mg, 5.1% filled simvastatin 80 mg, and 3.5% filled rosuvastatin 20 or 40 mg. Relative to patients prescribed low/moderate-intensity statins, a greater proportion of patients prescribed high-intensity statins had a history of coronary artery disease (73% vs 56%), myocardial infarction (27% vs 20%), and carotid stenosis (25% vs 16%). A greater proportion of patients prescribed high-intensity statins were also prescribed beta-blockers (69% vs 60%) and clopidogrel (69% vs 61%). A greater proportion of patients prescribed high-intensity statins tended to undergo angiography for claudication (46% vs 36%), and patients prescribed low/moderate-intensity statins tended to undergo angiography for critical limb ischemia (33% vs 42%) (Table 1). There was no difference in high-intensity statin use based on the year (p value for trend = 0.9). Therefore, only two thirds of patients with PAD undergoing angiography are prescribed any statin, and the majority is not prescribed high-intensity statins. Future quality measures should incorporate statin dosing among patients with PAD.
Characteristics of patients taking high-intensity vs. low/moderate intensity statins.
Clinical Science/Epidemiology – Other Poster 27
What Matters Most, Statin Intensity or Achieved LDL? – Evaluating Concordance of AHA/ACC Guidelines for Statin Use with Practice Outcomes at Stanford Hospital & Clinics
Elsie Gyang1, Nigam Shah2, Nicholas Leeper1
1Stanford University Hospital & Clinics, Stanford, CA, USA; 2Stanford University School of Medicine, Stanford, CA, USA
Introduction: Recommendations from the 2013 American College of Cardiology/American Heart Association Guidelines on the Assessment of Cardiovascular Risk have had a mixed reception. We set out to evaluate practice-based evidence from Stanford Hospital using structured and unstructured bioinformatics data to determine whether achieved LDL or statin intensity was more predictive of major adverse cardiac events (MACE).
Methods: We performed a retrospective cohort analysis of all adult patients ⩾ 21 years of age prescribed statin therapy between 1996 and 2015. Demographic and clinical variables were extracted from coded data and unstructured clinical text using a validated data extraction pipeline. To account for possible treatment selection bias we performed 1:1 propensity score matching to produce a patient cohort with similar demographic and clinical characteristics. McNemar’s chi-squared and conditional logistic regression analyses were performed to identify variables predictive of MACE.
Results: We identified 7378 adults on statin therapy with complete data. Patients were followed a mean of 3.3 years, 56% were male, 55% were Caucasian, and mean age was 64 years. Patients had a high burden of comorbidities (85% with HTN, 64% with Type II Diabetes, 58% with CAD, and 32% with PAD). Patients on high-intensity statins were matched with those on low-/moderate-intensity statins, producing a well-balanced cohort of 2056 patients. Statin intensity did not predict MACE (p=0.29) while achieved LDL was a significant predictor of outcomes (p=0.006). OR for MACE was 0.73 (95% CI 0.65–0.82) in patients with LDL of ⩽70 versus those with LDL >100. OR for MACE for LDL⩽70 versus LDL ⩾130 was 0.32 (95% CI 0.28–0.38).
Conclusions: Achieved LDL was a significant predictor of MACE outcome, while statin intensity was not. This finding implies that despite recent guidelines, statin therapy should continue to be aimed at achieving specific LDL targets rather than arbitrarily selecting statins based on intensity alone.
Clinical Science/Epidemiology – Thrombosis and Hemostasis Poster 28
The Changing Characteristics of Atrial Fibrillation Patients Treated with Warfarin
Andrew Putnam1, Xiaokui Gu1, Brian Haymart1, Eva Kline-Rogers1, Steve Almany2, Jay Kozlowski3, Gregory Krol4, Scott Kaatz5, James B Froehlich1, Geoffrey D Barnes1
1University of Michigan, Ann Arbor, MI, USA; 2William Beaumont Hospital, Royal Oak, MI, USA; 3Huron Valley-Sinai, Commerce, MI, USA; 4Henry Ford Hospital, Detroit, MI, USA; 5Hurley Medical Center, Flint, MI, USA
Background: It has been suggested that target specific oral anticoagulants are being preferentially used in low risk atrial fibrillation (AF) patients. Understanding the changing risk profile of new AF patients treated with warfarin is important for interpreting the quality of warfarin delivery through an anticoagulation clinic.
Methods: Six anticoagulation clinics participating in a quality improvement collaborative in Michigan enrolled 1293 AF patients between 2010 and 2014 as an inception cohort. Abstracted data included demographics, comorbidities, medication use and all INR values. Risk scores including CHADS2, CHA2DS2-VASc, HAS-BLED, SAMe-T2TR2, and Charlson Comorbidity Index were calculated for each patient at the time of warfarin initiation. The quality of anticoagulation was assessed using the Rosendaal time in the therapeutic range (TTR) during the first six months of treatment. Linear regression models were calculated for mean risk scores over time and Fisher’s exact tests were used to compare means.
Results: Between 2010 and 2014, patients initiating warfarin therapy for AF had an increasing mean CHADS2 and Charlson Comorbidity Index (p=0.02 for both), and a trend towards increasing mean CHA2DS2-VASc, HAS-BLED, and SAMe-T2TR2 scores (Table). The actual TTR remained unchanged over the study period (p=0.98).
Conclusions: Between 2010 and 2014, AF patients newly starting warfarin had mild increases in stroke and mortality risk with sustained quality of warfarin therapy. Assessing for similar trends in other anticoagulation clinics will help to determine if the sustained TTR is related to the quality improvement efforts of this multi-center collaborative.
Clinical Science/Epidemiology – Thrombosis and Hemostasis Poster 29
Impact of Body Mass Index on Periprocedural Risk of Bleeding and Thrombosis
Siva S Ketha1, Waldemar Wysokinski2, Robert McBane2
1Mayo Clinic, Jacksonville, FL, USA; 2Mayo Clinic, Rochester, MN, USA
Objectives: To determine the impact of BMI on the 3-month cumulative incidence of peri-procedural bleeding and thrombosis in chronically anticoagulated patients requiring temporary warfarin interruption for an invasive procedure and to determine the predictors of major bleeding in this clinical setting.
Methods: In a protocol driven, cohort study design, all patients referred to the Mayo Clinic Thrombophilia Center for peri-procedural anticoagulation management (1997–2004; n=2057), were followed forward in time to determine the 3-month cumulative incidence of peri-procedural bleeding (Kaplan-Meier product limit) and thrombosis. Patients were divided into 5 subgroups based on BMI. Decisions to ‘bridge’ with LMWH were based on estimated thromboembolism and bleeding risk.
Results: Indications for chronic anticoagulation included venous thromboembolism (36%), atrial fibrillation (23%), and mechanical heart valves (21%). Of the 2057 patients evaluated during this time period, 1415 (69%) patients received bridging therapy. The BMI for the entire patient subset ranged from 14.35 to 74.86.The 3-month cumulative incidence rates of major bleeding, thrombosis and death were 2.1%, 0.8% and 2.1%, respectively. Major bleeding rates, arterial and venous thromboembolism rates were not significantly different among patients in the various BMI subgroups. Univariate analysis for the predictors of peri-procedural bleeding showed prior bleeding, active cancer and bridging therapy with heparin to be significant (p<0.05) and these associations remained statistically significant (p<0.05) after controlling for potential confounders with adjusted Hazard ratios of 2.3, 3.2 and 2.3, respectively.
Conclusion: BMI is not an independent predictor of peri-procedural bleeding or thrombosis in chronically anticoagulated patients who are bridged with heparin peri-procedurally. Prior bleeding history, active cancer and bridging therapy with heparin are significant predictors of peri-procedural bleeding risk.
Clinical Science/Epidemiology – Thrombosis and Hemostasis Poster 31
Novel Inhibition of Tissue Factor Pathway for Prevention of Venous Stent Thrombosis
Siva S Ketha1, Waldemar Wysokinski2, Robert McBane2
1Mayo Clinic, Jacksonville, FL, USA; 2Mayo Clinic, Rochester, MN, USA
Objective: The use of venous stents for the treatment of acute or chronic venous obstruction is increasing dramatically. Optimal thromboprophylaxis following venous stent deployment has not been defined. Study objective was to determine the efficacy of tissue factor pathway inhibition for the prevention of venous stent thrombosis.
Methods: Pigs received either active site blocked recombinant human factor VIIa (0.5 mg/kg bolus plus 0.2 mg/kg/hr infusion; n=5) or saline (n=12). Thirty minutes later, iliac venous stents were deployed and the thrombus was allowed to propagate for 2 hours before harvesting. Thrombus size was measured by scintillation detection of autologous 111In-platelets and by venous thrombus weights.
Results: At a 2-fold prolongation of the prothrombin time, venous platelet deposition was reduced by 80% relative to vehicle controls (139 ± 50 vs 470 ± 376 × 106/cm2; p<0.001; Panel A). Venous thrombus weights were reduced by 95% (20 ± 28 mg vs 369 ±279 mg; p<0.0001; Panel B).
Conclusions: Platelet recruitment to venous stent thrombi occurs through initiation of the tissue factor pathway whereby thrombus formation is abolished by Factor VIIa inhibition. Specific targeting of the early stages of the tissue factor pathway may provide effective thromboprophylaxis following venous stenting.
Clinical Science/Epidemiology – Thrombosis and Hemostasis Poster 32
The Validity of ICD Codes Coupled with Imaging Procedure Codes for Identifying Venous Thromboembolic Events Using Administrative Data
Michael Sean McMurtry, Ghazi Alotaibi, Cynthia Wu
University of Alberta, Edmonton, AB, Canada
Purpose: To evaluate the accuracy of using a combination of ICD diagnostic codes and imaging procedure codes for identifying deep vein thrombosis (DVT) and pulmonary embolism (PE) within administrative databases.
Methods: Information from the Alberta Health (AH) inpatients and ambulatory care administrative databases in Alberta, Canada was obtained for subjects with a documented imaging study result performed at a large teaching hospital in Alberta to exclude venous thromboembolism (VTE) between 2000 and 2010. In 1361 randomly selected patients, the proportion of patients correctly classified by AH administrative data, using both ICD diagnostic codes and procedure codes, was determined for DVT and PE using diagnoses documented in patient charts as the gold standard.
Results: Of the 1361 patients, 712 had suspected PE and 649 had suspected DVT. The sensitivities for identifying patients with a PE or DVT using administrative data were 74.83% (95% CI: 67.01–81.62) and 75.24% (95% CI: 65.86–83.14), respectively. The specificities for PE or DVT were 91.86% (95% CI: 89.29–93.98) and 95.77% (95% CI: 93.72–97.30), respectively.
Conclusion: When coupled with relevant imaging codes, VTE diagnostic codes obtained from administrative data provide a relatively sensitive and very specific method to ascertain acute VTE.
Clinical Science/Epidemiology – Venous Disease Poster 33
Percutaneous Ablation of Incompetent Perforator Veins Comparing 980nm and 1470nm Lasers – 10 Year Experience
Mehul N Shah
Vascular Medicine Center, King of Prussia, PA, USA
Purpose: Historically incompetent perforator veins (IPV) have been treated by SEPS (Subfascial Endoscopic Perforator Surgery). Since 2004 it was realized that IPV is an important etiology of recurrent venous insufficiency and venous ulcers.
Methods: 660 patients with chronic superficial venous insufficiency and pathologic IPVs were evaluated and treated with Endovenous Laser Ablation with either laser. Criteria used reflux > 0.5 sec and IPV > 3.5 mm size. The IPV was visualized with ultrasound and the laser fiber was placed through a micropuncture 18G needle, Rowerson bulb and tumescent anesthetic infusion. Laser energy delivered. Results assessed by follow up ultrasound.
Conclusion: Excellent results were noted after treating 660 pathologic incompetent perforator veins using 980 nm and 1470 nm lasers over 10 years. 980 nm laser had higher incidence of pain and bruising as compared to the 1470 nm laser. Most recanalizations occurred in less than 9 months. Percutaneous Ablation of Perforators is an effective, safe, office based, minimally invasive and cost effective procedure. The efficacy and success rate/recanalization rate was not statistically significant between the two wavelength lasers.
Clinical Science/Epidemiology – Venous Disease Poster 34
Enhanced Platelet-Monocyte Aggregate Formation is Associated with Post-Surgical Deep Vein Thrombosis in Older Patients Undergoing Elective Orthopedic Surgery
Lauren Shih, David Kaplan, Larry W Kraiss, T Charlie Casper, Robert C Pendleton, Christopher L Peters, Guy A Zimmerman, Andrew S Weyrich, Shaohua Men, Matthew T Rondina
University of Utah, SLC, UT, USA
Background: Increased in vivo platelet activation may result in enhanced thrombin generation and contribute to the development of venous thromboembolism (VTE). Nevertheless, whether platelet activation is a risk factor for DVT in patients undergoing elective orthopedic surgery remains unexamined.
Methods: We prospectively enrolled 31 patients undergoing elective total knee or total hip arthroplasty. All patients were free of cardiovascular disease, active cancer, or other significant medical illnesses. Whole blood was drawn immediately pre-operatively and again 24 hours post-operatively. Platelet surface P-selectin expression, integrin activation, and heterotypic platelet-monocyte aggregation, indices of in vivo platelet activation, were assessed by flow cytometry. All patients received guideline-recommended VTE prophylaxis and underwent comprehensive duplex compression ultrasonography prior to discharge to assess for DVT and were also followed for PE.
Results: The mean age was 65.9±6.9 years and 58% were female. Overall, 41.9% of patients developed VTE and most events were considered clinically significant, resulting in systemic anticoagulation. Compared to patients without VTE, those that developed VTE had increased in vivo platelet activation, as determined by significantly enhanced platelet-monocyte aggregate formation post-operatively. Platelet surface p-selectin and integrin αIIbβ3 expression did not differ between patients with and without VTE, suggesting specific signaling events rather than global upregulation.
Conclusions: To our knowledge, this is the first prospective study to demonstrate identifying that in orthopedic surgery, enhanced platelet-monocyte aggregate formation, an index of in vivo platelet activation, predicts the development of post-surgical DVT. As activated platelets and platelet–monocyte interactions drive thrombo-inflammatory events, such as DVT, our findings identify new cellular contributions to post-surgical vascular thrombosis.
Clinical Science/Epidemiology – Venous Disease Poster 36
Role of Apixaban in Dialysis Patients after Percutaneous Endovenous Intervention for Deep Venous Thrombosis of the Lower Extremities
Mohsen Sharifi1, Wilbur Freeman2, Jose Jimenez1, Jeremy Berger2, Mirali Sharifi1, Frederic Schwartz2
1Arizona Cardiovascular Consultants and Vein Clinic, Mesa, AZ, USA; 2AT Still University, Mesa, AZ, USA
Background: Apixaban has received FDA approval for use in patients with severe renal impairment including those on dialysis. Patients with renal failure are particularly prone to venous obstruction due to higher propensity for deep venous thrombosis (DVT) as well as development of venous stenosis secondary to frequent catheter placement in the central venous circulation. Percutaneous endovenous intervention (PEVI) has been very effective in the treatment of acute DVT. There are a paucity of data on the use of apixaban after PEVI in patients with DVT.
Methods: We performed PEVI in the lower extremities of 42 patients who were on dialysis. Of these, 10 were on peritoneal dialysis and 32 on hemodialysis. The mean duration of dialysis was 5.3 ± 1.2 years. Patients had presented with leg edema, pain, induration, inability to walk and DVT. ‘Chronic DVT’ was the ultrasound diagnosis in 18 patients and ‘acute DVT’ in the remainder. All underwent PEVI with a combination of modalities including catheter directed thrombolysis and stenting. Subsequent to PEVI, the patients were placed on apixaban. Aspirin at 81 mg daily was given to 38 patients. Apixaban was given at 2.5 mg orally twice daily to patients ⩾75 years or <60 kg, and the remainder received 5 mg twice daily. Indefinite anticoagulation was recommended to 35 patients.
Results: At the mean follow-up of 10.1 ± 0.7 months, no major or minor bleeding occurred. There was no recurrent venous thromboembolic disease (VTE). No patient discontinued apixaban. The revised venous clinical severity score (VCSS) dropped from 9.3 ± 1.2 at index hospitalization to 5.6 ± 0.8 at follow up.
Conclusions: In dialysis patients, administration of apixaban following PEVI is highly safe and effective in prevention of recurrent VTE and improvement in VCSS score without the risk of bleeding.
Clinical Science/Epidemiology – Venous Disease Poster 37
A Systematic Approach to Evaluate for IVC Filter Retrieval: Single Center Report
Rory Detar1, Adam Porath2, Susan C Cox2, John Hansen2, Michael Bloch2
1University of Nevada School of Medicine, Reno, NV, USA; 2Renown Institute for Heart and Vascular Health, Reno, NV, USA
Introduction: Retrievable inferior vena cava (IVC) filters are commonly employed during acute hospitalization. Previous studies have documented low rates of IVC filter removal after discharge even in settings where the indication for the IVC filter has resolved. Retained IVC filters may be associated with significant long-term consequences including systemic thromboembolism, filter thrombosis, and filter migration. We developed a multi-disciplinary program to systematically identify all patients with an IVC filter placed at our institution and ensure that a disposition on that filter (i.e. remove or leave in place) was made in a timely fashion.
Methods: Clinical staff received a weekly list of all IVC filters placed, based on CPT code. While the ultimate decision for disposition of the IVC filter remained with the treating providers, staff made every attempt to facilitate that decision-making, including an evaluation with a vascular specialist if needed. The goal was to have a disposition made within six months after filter placement. Initial results of that process are presented here.
Results: Over 11 months (July 2013 – June 2014), 109 patients had an IVC filter placed at our institution. Of the 99 who remained alive at follow-up, 80 patients (81%) had a definitive disposition made within six months. Twenty-three patients (or 23%) of those alive had their IVC filter success-fully removed. Three (or 3%) had a failed attempt at removal.
Conclusion: Using a systematic, multi-disciplinary approach, we were able to make a definitive, timely disposition on the majority of IVC filters placed. This is an improvement from a prior study where 59.6% of patients had no follow-up.1 We also demonstrated a high rate of IVC filter retrieval. Future investigation will be needed to determine if this strategy leads to a decrease in associated complications or comorbidities.
Clinical Science/Epidemiology – Venous Disease Poster 38
National Incidence and Ten Year Trends in Deep Vein Thrombosis Following Total Knee and Total Hip Replacement
Anahita Dua1, Sapan S Desai2, Jennifer A Heller3
1Medical College of Wisconsin, Brookfield, WI, USA; 2Southern Illinois University, Springfield, IL, USA; 3Johns Hopkins University, Baltimore, MD, USA
Introduction: Total knee replacement (TKR) and total hip replacement (THR) are associated with an increased risk of deep vein thrombosis (DVT). Advances in DVT prophylaxis over the past decade have led to a decrease in DVT-related morbidity, but gender, racial, and other demographic factors that contribute to a higher risk of DVT are incompletely characterized. This study aimed to determine the incidence of DVT over the past decade and identify factors that were associated with an increased risk of DVT.
Methods: Patients who underwent TKR or THR between 2001 and 2011 were identified using the National Inpatient Sample (NIS). Demographics, comorbidities, length of stay (LOS) and mortality were determined. Differences between patients who developed a DVT and those who did not were determined using multivariate regression analysis. A Mann–Kendall analysis was done to evaluate all trends.
Results: Between 2001 and 2011, 1.1 million patients underwent TKR, and 550,000 underwent THR. The overall incidence of DVT decreased for TKR from 0.86% in 2001 to 0.45% in 2011, and decreased for THR from 0.55% to 0.24%. Patients at increased DVT risk were older (67.7 vs 66.8, p<0.001), male (37.9% vs 36.4%, p<0.001), African American (p<0.001), and had significant comorbidities including congestive heart failure, peripheral artery disease, and end stage renal disease. Mortality was significantly greater for patients who developed a DVT (0.4% following TKR and 1.7% for THR) and DVT almost doubled LOS.
Conclusion: Mortality is almost 8 times higher in patients who develop DVT. Increased age, male sex, African American race, and increased comorbidities are associated with DVT risk.