Synergistic influence of rivaroxaban on inflammation and coagulation biomarkers in patients with coronary artery disease and peripheral artery disease on aspirin therapy.

COMPASS study demonstrated efficacy of dual pathway inhibition with 2.5 mg twice daily rivaroxaban and aspirin in patients with polyvascular disease (coronary artery disease, peripheral arterial disease or both), the underlying mechanism of which is not clearly understood. In this Phase IV, prospective, open-label and randomized study, we hypothesize that treatment with rivaroxaban is associated with a reduction in platelet activation and aggregation, inflammation and coagulation markers. 30 patients will be randomly treated with aspirin (81 mg q.d.) or aspirin plus rivaroxaban (2.5 mg b.i.d.) for 12 weeks. Platelet aggregation, platelet activation and inflammation markers, thrombin generation kinetics and tissue factor-induced platelet-fibrin clot strength will be measured at baseline, and 4 and 12 weeks after randomization. Trial registration number: NCT04059679.

Contemporary predictors of extended postoperative hospital length of stay after carotid endarterectomy.

INTRODUCTION: Hospital length of stay (LOS) contributes to costs. Carotid endarterectomy (CEA) is performed frequently by vascular surgeons, making contemporary CEA LOS rates and predictors vital knowledge for quality evaluation and cost containment initiatives. METHODS: Using a prospective single-institution database, we retrospectively identified consecutive patients undergoing CEA from 2001 to 2011. Demographic and perioperative factors were prospectively collected. The primary end point was extended postoperative LOS (ELOS), defined as postoperative LOS ≥2 days. Factors associated with ELOS were analyzed in a multivariable logistic regression model. Rates of 1-year readmission and death were compared with the Kaplan-Meier method (log-rank test). RESULTS: Eight hundred forty patients underwent 897 CEAs with 39% of procedures among females and 35% for symptomatic disease. One hundred two (11.4%) patients were inpatients prior to the day of CEA ("preadmitted"); their preoperative days by definition are not included in ELOS. Median postoperative LOS was 1 day (interquartile range, 1-2). Four hundred fourteen patients (46.2%) had ELOS. Preadmission was associated with ELOS (72% vs 41%; P < .01) and ELOS patients were less likely to be discharged home (11.9% vs 1.5%; P < .01). There was no association between ELOS and unplanned 30-day postdischarge readmission (6.0% vs 7.0%; P = .59). On multivariable analysis, preoperative factors significantly associated with ELOS included preadmission (adjusted odds ratio [OR], 3.3; 95% confidence interval [CI], 1.9-5.7; P < .001), history of congestive heart failure (OR, 2.1; 95% CI, 1.1-4.2; P = .03), female gender (OR, 1.9; 95% CI, 1.4-2.6; P < .001), and history of chronic obstructive pulmonary disease (OR, 1.7; 95% CI, 1.0-2.9; P = .04). Operative factors included electroencephalography change (OR, 1.9; 95% CI, 1.2-3.2; P = .01), operating room start time after 12:00 pm (OR, 1.7; 95% CI, 1.2-2.4; P < .01), and total operating room time (OR, 1.5 per hour; 95% CI, 1.2-2.9; P < .01). Postoperative factors included transfer to intensive care unit (OR, 5.4; 95% CI, 3.1-9.4; P < .01), number of in-hospital postoperative complications (OR, 3.7; 95% CI, 2.2-6.5; P < .01), and Foley catheter placement (OR, 2.1; 95% CI, 1.3-3.4; P < .01). Over 1 year, ELOS was associated with increased hospital readmission (93.6% vs 84.7%; log-rank test, P < .01) and decreased survival (95.1% vs 98.3%; log-rank test, P < .01). CONCLUSIONS: Nearly half of CEA patients were discharged on or after postoperative day 2. Interventions on modifiable risk factors, such as early Foley catheter placement to prevent urinary retention and morning CEA scheduling, may decrease LOS. ELOS may identify a subset of patients at increased risk for long-term readmission and mortality.

Mineralocorticoid receptor expression in human venous smooth muscle cells: a potential role for aldosterone signaling in vein graft arterialization.

Experimental studies have suggested a role for the local renin-angiotensin-aldosterone system in the response to vascular injury. Clinical data support that aldosterone, via activation of the mineralocorticoid receptor (MR), is an important mediator of vascular damage in humans with cardiovascular disease. In mineralocorticoid-sensitive target tissue, aldosterone specificity for MR is conferred enzymatically by the cortisol-inactivating enzyme 11ß-hydroxysteroid-dehydrogenase-2 (11ßHSD2). However, the role of MR/aldosterone signaling in the venous system has not been explored. We hypothesized that MR expression and signaling in venous smooth muscle cells contributes to the arterialization of venous conduits and the injury response in vein bypass grafts. MR immunostaining was observed in all samples of excised human peripheral vein graft lesions and in explanted experimental rabbit carotid interposition vein grafts, with minimal staining in control greater saphenous vein. We also found upregulated transcriptional expression of both MR and 11ßHSD2 in human vein graft and rabbit vein graft, whereas control greater saphenous vein expressed minimal MR and no detectable 11ßHSD2. The expression of MR and 11ßHSD2 was confirmed in cultured human saphenous venous smooth muscle cells (hSVSMCs). Using an adenovirus containing a MR response element-driven reporter gene, we demonstrate that MR in hSVSMCs is capable of mediating aldosterone-induced gene activation. The functional significance for MR signaling in hSVSMCs is supported by the aldosterone-induced increase of angiotensin II type-1 receptor gene expression that was inhibited by the MR antagonist spironolactone. The upregulation of MR and 11ßHSD2 suggests that aldosterone-mediated tissue injury plays a role in vein graft arterialization.

Infrainguinal bypass is associated with lower perioperative mortality than major amputation in high-risk surgical candidates.

BACKGROUND: Major amputation is often selected over infrainguinal bypass in patients with severe systemic comorbidities because it is assumed to have lower perioperative risks, yet this assumption is unproven and largely unexamined. METHODS: The 2005 to 2008 National Surgical Quality Improvement Project (NSQIP) database was used to identify all patients undergoing either infrainguinal bypass or major amputation using procedural codes. Patients with systemic or local infections were excluded. A subset of high-risk patients were then defined as American Society of Anesthesiologists (ASA) class 4 or 5, or ASA class 3 with renal failure, dyspnea at rest, ventilator dependence, recent congestive heart failure, or recent myocardial infarct. Propensity score matching was used to obtain two high-risk patient groups matched for preoperative characteristics. RESULTS: No significant differences in demographic, preoperative, or anesthetic variables were found between the matched, high-risk amputation or bypass groups (792 and 780 patients, respectively). Bypass was associated with a lower 30-day postoperative mortality than amputation (6.54% vs 9.97%; P = .0147). Amputation was associated with higher rates of pulmonary embolism (0.9% vs 0% for amputation vs bypass groups, respectively; P = .009) and urinary tract infection (5.2% vs 2.7%; P = .01), while bypass was associated with higher rates of return to the operating room (14.1% vs 27.6%; P < .001) and a trend toward higher postoperative transfusion requirements (0.9% vs 2.1%; P = .054). The postoperative time to discharge did not differ between the two groups. CONCLUSION: The decision to perform an infrainguinal bypass or amputation should depend on well-established predictors of graft patency and functional success rather than presumptions about different perioperative risks between the two procedures.

Results of second-time angioplasty and stenting for femoropopliteal occlusive disease and factors affecting outcomes.

OBJECTIVE: Repeat percutaneous endoluminal interventions for femoropopliteal occlusive disease are common, but the outcomes are poorly understood. We sought to determine the results of second-time femoropopliteal percutaneous transluminal angioplasty/stenting (SPTAS) and identify factors associated with success or failure of a continued endoluminal revascularization strategy. METHODS: A retrospective review of patients undergoing multiple percutaneous endoluminal lower extremity interventions at a single institution from 2002 and 2009 identified 70 SPTAS in 70 limbs. Patient comorbidities, anatomic severity of disease, and procedural characteristics were analyzed with respect to outcomes with descriptive statistics, Kaplan-Meier curves, and Cox proportional hazards modeling. Patency rates were determined from the time of SPTAS. RESULTS: Patients included 37 men (63%) and 22 women (27%) at a mean age of 70 ± 10 years. Indications for SPTAS included claudication in 54 limbs (77%) and critical limb ischemia (CLI) in 16 (23%). Median time from the initial endoluminal intervention to SPTAS was 330 days. Lesion TransAtlantic InterSociety Consensus II (TASCII) classification was A in 18 (25.7%), B in 18 (25.7%), C in 25 (35.7%), and D in 9 (12.9%). Technical success was achieved in 68 (97%) with low rates of intraprocedural (10%) and postprocedural (4%) complications as well as initial clinical improvement in 61 (87%) patients. Over a median follow-up of 22.9 months following SPTAS, 2-year primary patency, secondary patency, limb salvage (in patients with CLI), and survival were 33% ± 7%, 63% ± 7%, 87% ± 9%, and 88% ± 5%, respectively. Cox proportional hazard modeling showed that SPTAS within 180 days of the initial endovascular intervention was the only significant predictor of failure of primary patency (hazard ratio, 2.65; 95% confidence interval, 1.4-5.2) and secondary patency (hazard ratio, 3.1; 95% confidence interval, 1.4-7.1) of SPTAS. CONCLUSIONS: Second-time femoropopliteal angioplasty/stenting has excellent technical success but limited midterm primary and secondary patency. Early failure of the initial endovascular intervention strongly predicts poor outcome following SPTAS and in this cohort was more significant than comorbidities, anatomic factors, or procedural characteristics. These data suggest that after early endovascular failure, alternatives to a continued endoluminal strategy should be adopted.

Favorable outcomes with in situ techniques for surgical repair of complex renal artery aneurysms.

OBJECTIVE: The optimal method of operative management of complex branch renal artery aneurysms (RAAs) remains unclear, with recent reports predominantly espousing endovascular and ex vivo repair. We sought to determine the long-term outcome of RAA repair performed with autogenous in situ techniques. METHODS: This was a cohort study of patients undergoing surgical repair of RAAs identified from our prospective vascular division registry (1984-2009). RESULTS: Twenty-six RAAs were repaired in 24 patients (17 women, 7 men; mean age, 52 ± 16 years). Mean size was 2.3 ± 0.7 cm (range, 0.7-4.0 cm). Twenty RAAs were repaired based on size and six for hypertension alone. Multiple RAAs were present in 13 patients (54%). Associated conditions included hypertension in 24 (100%), fibromuscular dysplasia in 6 (25%), coexistent renal artery stenosis in 6 (25%), and aortic aneurysm in 3 (12.5%). Reconstruction of first- or second-order branches was required in 25 RAAs (96%). In situ techniques were used in 22 repairs and included resection combined with autogenous vein bypass and interposition in 11, primary anastomosis to conjoined outflow vessels in 3, and aortic reimplantation in 2. Aneurysmorrhaphy was combined with vein patch angioplasty in 6, exclusion in 2, tailored primary closure in 1, and autogenous bypass in 1. Four patients underwent ex vivo reconstruction. Perioperative mortality was 0% and morbidity was 11.5%, including one nephrectomy during ex vivo repair for immediate thrombosis. Renal function was preserved (preoperative creatinine, 0.94 ± 0.3 vs postoperative creatinine 1.06 ± 0.4 mg/dL; P = .11). Systolic (SBP) and diastolic blood pressure (DBP) control improved after operation: preoperative SBP 142 ± 18 vs postoperative SBP 130 ± 15 mm Hg (P = .007) and preoperative DBP 86 ± 14 vs postoperative DBP 78 ± 10 mm Hg (P = .01). Long-term patency was evaluated in 18 reconstructions (69%) by duplex imaging or contrast radiography at an average long-term follow-up of 99 months (range, 1-300 months) and was 94%. Five-year freedom from rupture and survival by the Kaplan-Meier method was 100%. CONCLUSION: In situ techniques allow repair of complex RAAs involving branch vessels with minimal morbidity, improved blood pressure control, and maintenance of renal function. This operative approach further provides excellent long-term patency and survival in this relatively young patient population.

Acute infectious pseudoaneurysm of the descending thoracic aorta and review of infectious aortitis.

Thoracic aortic wall disruptions may occur secondary to trauma, surgical interventions, infection, or autoimmune or idiopathic inflammatory disorders. Such vessel wall disruption can lead to aortic dissections, aneurysm development, or more commonly, pseudoaneurysm (PSA) formation. Although aortic wall infections as an antecedent to mycotic aneurysms have been recognized since the 17th century, there has been a temporal evolution in the development of this disease. Prior to the antibiotic era they were commonly associated with endocarditis or syphilis. More recently, however, they are associated with infection of a damaged atherosclerotic area of the aorta and secondary hematogenous or contiguous seeding. We report the first case of the rapid development of a pseudoaneurysm in the descending thoracic aorta attributable to an infection of a contiguous esophageal duplication cyst by a diagnostic esophageal ultrasound (EUS) fine-needle aspiration. A literature review of mycotic thoracic aortic aneurysms and pseudoaneurysms is also presented.

Angiotensin II and tumor necrosis factor-alpha upregulate survivin and Kruppel-like factor 5 in smooth muscle cells: Potential relevance to vein graft hyperplasia.

BACKGROUND: Survivin (SVV) is a unique inhibitor of apoptosis protein (IAP) that regulates both apoptosis and mitosis. Recent work suggests that SVV plays a critical role in the vascular injury response, but the molecular pathways remain unclear. METHODS: We examined the expression of SVV and the transcription factor, KLF5, in human venous smooth muscle cells (VSMC) by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis after treatment with angiotensin II (Ang II) or tumor necrosis factor-alpha (TNF-alpha). An adenoviral construct expressing SVV or GFP was also employed to assess effects on KLF5 expression. A rabbit carotid interposition vein graft model was used to assess the relevance of KLF5 to bypass graft healing. RESULTS: Stimulation of VSMC with Ang II and TNF-alpha led to a rapid upregulation of KLF5 expression, and a later increase in SVV, which was cell-cycle independent. Overexpression of SVV in VSMC led to an early and persistent induction of KLF5. KLF5 was upregulated in rabbit vein grafts early (1 day) after grafting. CONCLUSIONS: We speculate that SVV is a central point of convergence of multiple signaling pathways in vascular injury, and that it regulates the local amplification of these pathways in the vessel wall.