Faculty Bibliography

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:Quality metrics were developed to improve outcomes after carotid artery revascularization; however, few studies have evaluated regional differences in perioperative outcomes. This study aimed to evaluate regional variation in mortality and perioperative outcomes after carotid endarterectomy (CEA) and carotid artery stenting (CAS). METHODS:analysis, Fisher exact test, and t-test, where appropriate. RESULTS:A total of 78,467 carotid interventions were identified; 85% were CEAs, with 69% of those asymptomatic. Within CAS, 39% were asymptomatic. Perioperative stroke/death varied across regions within both CAS groups (asymptomatic, 0%-5.8% [P = .03]; symptomatic, 2.4%-8.1% [P = .1]), and several regions did not meet the American Heart Association (AHA) guidelines of 3% for asymptomatic patients and 6% for symptomatic patients, which persisted after risk adjustment. For CEA, the stroke/death rates fell within the standards set by the AHA guidelines in all regions for both the unadjusted and risk-adjusted models; however, there was significant regional variation in the cohorts (asymptomatic, 0.9%-3.1% [P < .01]; symptomatic, 1.3%-4.9% [P < .01]). Variation in 30-day mortality was significant in symptomatic patients (asymptomatic: CEA, 0%-1.3% [P = .2], CAS, 0%-2.4% [P = .2]; symptomatic: CEA, 0%-1.8% [P < .01], CAS, 0%-4.6% [P = .01]). Rates of in-hospital stroke, postoperative myocardial infarction, prolonged length of stay (>2 days), and use of intravenous blood pressure medications all varied significantly across the regions. After CEA, there was significant variation in the rates of cranial nerve injuries (asymptomatic, 0.9%-4.9% [P < .01]; symptomatic, 1.5%-7.7% [P < .01]), return to the operating room (asymptomatic, 0.9%-3.4% [P < .01]; symptomatic, 0.6%-3.4% [P = .02]), and discharge on antiplatelet and statin (asymptomatic, 75%-87% [P < .01]; symptomatic, 78%-91% [P < .01]). After CAS, significant variation was found in the rates of access site complications (asymptomatic, 2.3%-18.2% [P < .01]; symptomatic, 1.4%-16.9% [P < .01]) and discharge on dual antiplatelet therapy (asymptomatic, 79%-94% [P < .01]; symptomatic, 83%-93% [P < .01]). CONCLUSIONS:Unwarranted regional variation exists in outcomes after carotid artery revascularization across the regions of the VQI. Significant variation was seen in a number of outcomes for which quality metrics currently exist, such as length of stay and discharge medications. In addition, after CAS, several regions failed to meet the AHA guidelines for stroke and death. Given these results, quality improvement projects should be targeted to improve adherence to current guidelines to promote best practices.

BACKGROUND:Peripheral artery disease (PAD), a diffuse manifestation of atherothrombosis, is a major cardiovascular threat. Although platelets are primary mediators of atherothrombosis, their role in the pathogenesis of PAD remains unclear. OBJECTIVES/OBJECTIVE:The authors sought to investigate the role of platelets in a cohort of symptomatic PAD. METHODS:The authors profiled platelet activity, mRNA, and effector roles in patients with symptomatic PAD and in healthy controls. Patients with PAD and carotid artery stenosis were recruited into ongoing studies (NCT02106429 and NCT01897103) investigating platelet activity, platelet RNA, and cardiovascular disease. RESULTS:Platelet RNA sequence profiling mapped a robust up-regulation of myeloid-related protein (MRP)-14 mRNA, a potent calcium binding protein heterodimer, in PAD. Circulating activated platelets were enriched with MRP-14 protein, which augmented the expression of the adhesion mediator, P-selectin, thereby promoting monocyte-platelet aggregates. Electron microscopy confirmed the firm interaction of platelets with monocytes in vitro and colocalization of macrophages with MRP-14 confirmed their cross talk in atherosclerotic manifestations of PAD in vivo. Platelet-derived MRP-14 was channeled to monocytes, thereby fueling their expression of key PAD lesional hallmarks and increasing their directed locomotion, which were both suppressed in the presence of antibody-mediated blockade. Circulating MRP-14 was heightened in the setting of PAD, significantly correlated with PAD severity, and was associated with incident limb events. CONCLUSIONS:The authors identified a heightened platelet activity profile and unraveled a novel immunomodulatory effector role of platelet-derived MRP-14 in reprograming monocyte activation in symptomatic PAD. (Platelet Activity in Vascular Surgery and Cardiovascular Events [PACE]; NCT02106429; and Platelet Activity in Vascular Surgery for Thrombosis and Bleeding [PIVOTAL]; NCT01897103).

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.

Background: Patients with peripheral artery disease (PAD) are at increased risk of atherothrombotic events and benefit from platelet inhibiting therapies. The EUCLID trial demonstrated no significant benefit from ticagrelor versus clopidogrel for the reduction of cardiovascular or limb events in patients with PAD. Aims: The EUCLID platelet substudy aimed to compare the antiplatelet effects of ticagrelor and clopidogrel in patients with PAD. Methods: Patients were randomized to receive either clopidogrel (75 mg daily) or ticagrelor (90 mg twice daily). The effect of study drug was studied in 75 patients during maintenance therapy (>=6-weeks post randomization). In 42 patients, platelet inhibition was measured at baseline and after 2-and 6-weeks of study drug (=12 hrs after last dose). In all patients, pharmacodynamic assessments were made using light transmission aggregometry (in response to ADP 5 and 20uM, collagen 1ug/ml and arachidonic acid [AA] 150uM), VerifyNow P2Y12, and VASP phosphorylation. Results: During maintenance therapy, ticagrelor achieved lower platelet activity of ADP-induced platelet aggregation than clopidogrel (maximum platelet aggregation to ADP 5uM, 39% vs. 60. 5%, P< 0. 001; ADP 20uM 51% vs. 67. 5%, P=0. 004; VerifyNow, 74 vs. 165 PRU, P< 0. 001; VASP 16. 9 vs. 45. 8 PRI, P< 0. 001). High on-treatment platelet reactivity was observed more frequently in the clopidogrel treated group (P< 0. 05 for each ADP-mediated assay). The effect at 14-days and 6-weeks was consistent with a greater platelet inhibition with ticagrelor compared with clopidogrel. The inhibition of collagenor AA-induced platelet aggregation was not different between groups. Conclusions: In patients with PAD, ticagrelor achieved greater inhibition of ADP mediated platelet activity versus clopidogrel. The inhibition of non-ADP mediated platelet activity was not different between groups. Despite greater platelet inhibition, ticagrelor was not superior to clopidogrel for the reduction of cardiovascular events in patients with PAD