Faculty Bibliography

Venous thromboembolism (VTE), comprised of deep vein thrombosis and pulmonary embolism, is a common health problem both in the United States and worldwide, with significant associated morbidity and mortality. Despite multiple known genetic and situational risk factors, an estimated 30% of all events remain classified as idiopathic, demonstrating a significant knowledge gap in the pathophysiology VTE. While platelets are well established as an essential contributor to thrombus formation and there has been recent interest in the role of neutrophil extracellular traps, specific cell types and pathways involved in the pathogenesis of VTE remain uncertain. In this study, our primary aims were to define a unique transcriptional signature for VTE and to identify the types of cells and specific pathways involved in development of VTE. Whole blood was collected in PAX gene tubes and RNA sequencing for coding mRNA was performed in an unbiased manner in 201 patients with prevalent VTE as well as 43 healthy controls. We used a bioinformatics approach to develop a unique signature for VTE by identifying differentially expressed genes, developing cell-type modules, and ascertaining pathways driving differentially expressed transcripts. We performed additional analyses on subgroups of patients with idiopathic VTE, patients with incident VTE, and VTE patients matched to healthy controls by age and sex. We went on to use machine learning methods to learn models that best differentiate VTE patients from healthy controls and validated it on a left out test set within our VTE population. Genes specific to neutrophils, erythrocytes, and platelets, in that order, were most significantly upregulated in patients with VTE compared to healthy controls. Genes related to T-cells were downregulated. Pathway analysis revealed upregulated neutrophil activation and degranulation, erythrocyte differentiation and homeostasis, and platelet degranulation. A gene signature of 217 transcripts was outstanding at differentiating patients with VTE versus healthy controls (AUC 0.94). Following adjustment for age, sex, and race/ethnicity our genetic signature remained significantly robust at differentiating patients with VTE versus controls (AUC 0.83). Our expression signature remained stable across patients with idiopathic VTE (AUC 0.93), and in patients who went on to develop future VTE events (AUC 0.95). In summary, we have demonstrated a whole blood transcriptional signature for prevalent and incident VTE. Genes related to neutrophils, erythrocytes, and platelets are upregulated in patients with VTE and genes related to T-cells were downregulated. These findings suggest an active role of cell types once thought to be passively entrapped within thrombus and provide new areas of study to establish the pathophysiology of VTE

Synovial Chondromatosis (SC) is a rare, benign synovial growth most frequently involving the knee or hip joint. Common presenting symptoms include pain throughout the affected joint, reduced range of motion and a palpable mass. We present an unusual case of SC presenting with symptoms of chronic venous stasis ulcer. A 49-year-old patient presented with swelling, hyperpigmentation and ulcerations of his right lower extremity. Work-up including duplex and CT scan revealed a calcified mass in the hip joint, highly suspicious for Synovial Chondromatosis. A joint surgical approach from a Vascular and Orthopaedic surgeon successfully removed the growths and decompressed the surrounding vessels. The mass effect of the SC on overlying veins resulted in obstruction of venous return due and subsequent venous stasis ulcerations and symptoms of venous hypertension. We present this case due to the unique vascular sequelae related to the Synovial Chondromatosis in order to explore this as a new diagnosis to consider in patients who present with venous stasis ulceration and radiographic findings consistent with SC.

BACKGROUND AND AIMS/OBJECTIVE:Diabetes mellitus is a coronary heart disease (CHD) risk-equivalent for the outcome of peripheral vascular disease. The impact of diabetes with comorbid risk factors on the outcome of peripheral vascular disease remains unexplored. METHODS:We performed a cross-sectional analysis of participants in Lifeline Vascular Screening Inc. age 40-90 who were screened for peripheral vascular disease, defined as lower extremity peripheral artery disease (PAD, ABI <0.9) and/or carotid artery stenosis (CAS, internal CAS ≥50%). CHD was defined as prior myocardial infarction or revascularization. Risk factors included hypertension, hyperlipidemia, smoking, obesity, sedentary lifestyle and family history of cardiovascular disease. RESULTS:Among 3,517,804 participants, PAD and CAS was identified in 4.4% and 3.7%, respectively. Diabetes was identified in 376,528 participants, 324,680 (86%) of whom did not have CHD. Among diabetic participants without CHD, prevalence of PAD increased with 1-2 (4.3%), 3-4 (7.3%), and ≥5 (12.0%) comorbid risk factors (p trend < 0.0001). The pattern was similar for CAS (3.7%, 6.2%, 8.8%, p trend < 0.0001). Compared to participants without diabetes, those with diabetes and 1-2, 3-4 and ≥5 risk factors had increasing odds of PAD and CAS after adjustment for age, sex and race/ethnicity (1.0, 95% CI 0.98-1.06; 1.8, 95% CI 1.8-1.89; 3.5, 95% CI 3.43-3.64, respectively, p trend < 0.0001). By comparison, in nondiabetic participants, CHD increased odds of PAD and CAS by 2-fold (2.06, 95% CI 2.02-2.1; 2.19, 95% CI 2.15-2.23 respectively). CONCLUSIONS:Diabetes, particularly with comorbid risk factors, confers increased odds of PAD and CAS, even in the absence of CHD. Counseling regarding screening and prevention for peripheral vascular disease among individuals with diabetes and multiple risk factors may be useful.

CONTEXT/BACKGROUND:Over the past decade, a number of endovascular approaches have evolved to treat aortic aneurysms with anatomy that is not amenable to traditional endovascular repair, although the optimal practice and referral patterns remain in question. The Zenith fenestrated (Z-Fen) endograft (Cook Medical) represents the first commercially available fenestrated graft product in the United States. OBJECTIVE:We aim to quantify practice patterns in Z-Fen use during the first 5 years of commercial availability, and we identify predictors of high and low uptake. DESIGN, SETTING, AND PATIENTS/METHODS:This is a retrospective review of complete order records for Z-Fen endografts since June 2012. We performed univariate and multivariate regressions of predictors that surgeons and centers would be in the top and bottom quartiles of annual Z-Fen use. RESULTS:Since June 15, 2012, 744 surgeons have been trained to use Z-Fen, and 4133 cases have been performed at 409 trained centers. The average annual number of cases per trained surgeon was 4.46 [95% confidence interval (CI), 3.58-5.70]; however, many surgeons performed few or no cases following training, and there was a skew toward users with low average annual volumes (25th percentile 1.23, 50th percentile 2.35, 75th percentile 4.93, and 99th percentile 33.29). Predictors of high annual use in the years following training included academic center (aOR 5.87, P = .001) and training within the first 2 years of availability (aOR 46.23, P < .001). CONCLUSION/CONCLUSIONS:While there is literature supporting the safety and efficacy of Z-Fen, adoption has been relatively slow in an era when the vast majority of vascular surgeons have advanced endovascular skills. Given the training and resources required to use fenestrated or branched aortic endovascular devices, referral patterns should be determined and training should be focused on centers with high expected volumes.

OBJECTIVE:The Gore Iliac Branch Endoprosthesis (IBE; W. L. Gore & Associates, Flagstaff, Ariz) has recently been approved by the Food and Drug Administration for treatment of common iliac artery (CIA) aneurysms. Despite early excellent results in clinical trial, none of 63 patients were treated for bilateral iliac aneurysms. The goal of this study was to examine real-world experience using the Gore IBE for bilateral CIA aneurysms. METHODS:A retrospective review of an international multicenter (16 U.S., 8 European) experience using the Gore IBE to treat bilateral CIA aneurysms was performed. Cases were limited to those occurring after Food and Drug Administration approval (February 2016) in the United States and after CE mark approval (November 2013) in Europe. Demographics of the patients, presentation, anatomic characteristics, and procedural details were captured. RESULTS:There were 47 patients (45 men; mean age, 68 years; range, 41-84 years) treated with bilateral Gore IBEs (27 U.S., 20 European). Six patients (12.7%) were symptomatic and 12 (25.5%) patients were treated primarily for CIA aneurysm (aorta <5.0 cm). Mean CIA diameter was 40.3 mm. Four patients had aneurysmal internal iliac arteries (IIAs). Two of these were sealed proximally at the IIA aneurysm neck and two required coil embolization of IIA branches to achieve seal in the largest first-order branches. Technical success was achieved in 46 patients (97.9%). No type I or type III endoleaks were noted. There was no significant perioperative morbidity or mortality. IIA branch adjunctive stenting was required in four patients (one IIA distal dissection, three kinks). On follow-up imaging available for 40 patients (85.1%; mean, 6.5 months; range, 1-36 months), 12 type II endoleaks (30%) and no type I or type III endoleaks were detected. Two of 80 (2.5%) IIA branches imaged were occluded; one was intentionally sacrificed perioperatively. CONCLUSIONS:Preservation of bilateral IIAs in repair of bilateral CIA aneurysms can be performed safely with excellent technical success and short-term patency rates using the Gore IBE device. Limb and branch occlusions are rare, usually are due to kinking, and can almost always be treated successfully with stenting.

BACKGROUND: Reversal of flow in the vertebral artery (RFVA) is an uncommon finding on cerebrovascular duplex ultrasound examination. The clinical significance of RFVA and the natural history of patients presenting with it are poorly understood. Our objective was to better characterize the symptoms and outcomes of patients presenting with RFVA. METHODS: A retrospective review was performed of all cerebrovascular duplex ultrasound studies performed at our institution between January 2010 and January 2016 (N = 2927 patients). Individuals with RFVA in one or both vertebral arteries were included in the analysis. RESULTS: Seventy-four patients (74/2927 patients [2.5%]) with RFVA were identified. Half of the patients were male. Mean age at the time of the first ultrasound study demonstrating RFVA was 71 years (range, 27-92 years); 78% of patients had hypertension, 28% were diabetic, and 66% were current or former smokers. Indications for the ultrasound examination were as follows: 44% screening/asymptomatic, 7% anterior circulation symptoms, 20% posterior circulation symptoms, 28% follow-up studies after cerebrovascular intervention, and 5% upper extremity symptoms. At the time of the initial ultrasound examination, 21 patients (28%) had evidence of a prior carotid intervention (carotid endarterectomy or carotid stenting), 21 patients had evidence of moderate (50%-79%) carotid artery stenosis (CAS) in at least one carotid artery, and 12 patients (16%) had evidence of severe (>80%) CAS. Of the 15 patients presenting with posterior circulation symptoms, 11 (73%) had evidence of concomitant CAS. In contrast, 22 of the 59 patients (37%) without posterior circulation symptoms had duplex ultrasound findings of CAS (P = .01). The mean duration of follow-up was 28 +/- 22 months. Follow-up data were available for 63 patients (85%), including the 15 patients who presented with posterior circulation symptoms. Of these 15 patients, 5 underwent subclavian artery revascularization, including balloon angioplasty and stenting in 4 patients and open/hybrid revascularization in 1 patient. Five individuals were awaiting intervention. Three patients underwent carotid endarterectomy for CAS, with resultant improvement in posterior circulation symptoms. Finally, one patient was deemed too high risk for intervention, and one patient was found to have an alternative cause for symptoms. The remaining 59 patients continued to be asymptomatic during follow-up. One patient progressed to vertebral artery occlusion, and six patients had progression of CAS. CONCLUSIONS: Symptomatic RFVA responds well to intervention, including subclavian artery stenting and carotid intervention in patients with CAS. The majority of patients with this finding are asymptomatic at the time of presentation. Although progression of vertebral artery disease is rare, these patients may benefit from monitoring for progression of CAS with surveillance ultrasound.

Aortocaval fistula (ACF) is a lethal complication of aortic aneurysmal disease. Traditional treatment of ACF involves open surgical approaches to fistula ligation and repair of the great vessels, with a high mortality secondary to bleeding and cardiac compromise. We present the case of a 28-year-old man with a chronic ACF with concomitant aortic pseudoaneurysms secondary to penetrating trauma treated with a fenestrated endograft.

Background/UNASSIGNED:Venous thromboembolism (VTE) is a common vascular complication of non-cardiac surgery. Methods/UNASSIGNED:We evaluated national trends in perioperative in-hospital VTE incidence, management, and outcomes using a large database of hospital admissions from the United States. Patients aged ≥ 45 years undergoing major non-cardiac surgery from 2005 to 2013 were identified from the National Inpatient Sample. In-hospital perioperative VTE was defined as lower extremity deep vein thrombosis (DVT) or pulmonary embolism (PE), and the incidence was evaluated over time. Multivariable regression models with demographics and comorbidities as covariates were generated to estimate adjusted odds ratios (aOR). Results/UNASSIGNED:Major non-cardiac surgery was performed in 9,431,442 hospitalizations that met inclusion criteria, and perioperative VTE occurred in 99,776 patients (1,057 per 100,000), corresponding to an annual incidence of ≈53,000 after applying sample weights. Over time, perioperative VTE per 100,000 surgeries increased by 135 (95% CI 107 - 163), from 925 in 2005 to 1,060 in 2013 (p for trend <0.001; aOR [for 2013 versus 2005] 1.22, 95% CI 1.19 - 1.26), due to increases in non-fatal VTE rates (from 840 [per 100,000 surgeries] in 2005 to 987 in 2013; p for trend <0.001). Perioperative VTE occurred most frequently in patients undergoing thoracic (2.0%) and vascular surgery (1.8%). Mortality was higher in patients with VTE than those without VTE (aOR 3.12, 95% CI 3.05 - 3.20). Conclusions/UNASSIGNED:Perioperative VTE occurs in approximately 1% of patients ≥45 years undergoing major non-cardiac surgery, with increasing incidence of non-fatal VTE over time.