A patient with multiple paradoxical emboli.

We present a case report of simultaneous pulmonary emboli and paradoxical embolism to the cerebellum causing a stroke and severe ischemia to the left leg. This patient had risk factors for thromboembolic events that included autoimmune disease, cancer, and recent pelvic surgery. The presence of a perforate foramen ovale was suspected on his initial presentation and confirmed with echocardiography. For acute leg ischemia, this patient underwent emergent left common femoral embolectomy. The potential benefit of immediate anticoagulation had to be weighed against the risk of hemorrhagic transformation of his cerebellar stroke with possible compression of the fourth ventricle. In the end, full anticoagulation was delayed with interval placement of a retrievable inferior vena cava filter. This case illustrates the challenges faced in treating a patient with multiple paradoxical emboli.

Sleep-induced amaurosis fugax.

Amaurosis fugax is a manifestation of retinal ischemia, commonly described in the setting of carotid atherosclerotic disease. Thromboembolic, and less frequently, hemodynamic mechanisms have been described as responsible for producing negative symptoms of transient monocular vision loss during periods of wakefulness. We report an unusual presentation in which the patient became symptomatic during sleep. Initially, photopsias-positive symptoms were experienced, which caused the patient to awaken; this was immediately followed by transient monocular vision loss. Carotid endarterectomy was curative.

Predictors of clinically significant postprocedural hypotension after carotid endarterectomy and carotid angioplasty with stenting.

OBJECTIVES: Significant hypotension after carotid endarterectomy (CEA) and carotid angioplasty with stenting (CAS) has been correlated with adverse outcomes. The objective of this study was to determine risk factors that predict hypotension after patients undergo CEA and CAS. METHODS: The review included 1474 CEA patients and 157 CAS patients who underwent procedures from 2002 to 2008. Specific patient characteristics, such as comorbid diseases, degree of carotid stenosis, presence of neurologic symptoms, and preprocedure medications, were assessed. Also reviewed were specific postprocedural clinical outcomes, including hypotension requiring pressors, myocardial infarction, stroke, death, and hospital length of stay. RESULTS: The incidence of clinically significant hypotension was 12.6% in CEA patients and 35% in CAS patients (P < .001). Clinically significant hypotension was correlated with increased postprocedural myocardial infarction (2.1% vs 0.5%, P = .022), increased mortality (2.1% vs 0.1%, P < .001), and length of stay >2 days (46.3% vs 27.4%, P = .01). Hypotension was not associated with increased postprocedural strokes (0.8% vs 0.6%, P = .75) or recurrent neurologic symptoms (0.4% vs 0.3%, P = .55). Preoperative nitrate use predicted a greater incidence of postprocedural hypotension (P = .043). A history of tobacco use was correlated with postprocedure hypotension (P = .033). Preprocedural strokes, the use of calcium channel blockers, beta-blockers, angiotensin-converting enzyme inhibitors, prior myocardial infarction, degree of preprocedural carotid stenosis, type of stent, previous ipsilateral and contralateral interventions, and female gender did not correlate with postprocedural hypotension (P >.05). CONCLUSIONS: Postprocedural hypotension occurs more commonly with CAS than CEA and is associated with increased postprocedural myocardial infarction and length of stay, and death. Nitrates and tobacco use predict a higher incidence of postprocedural hypotension. High-risk patients should be aggressively managed to prevent the increased morbidity and mortality due to postprocedural hypotension.

Predictive value of reactive hyperemia for cardiovascular events in patients with peripheral arterial disease undergoing vascular surgery.

OBJECTIVE: Reactive hyperemia is the compensatory increase in blood flow that occurs after a period of tissue ischemia, and this response is blunted in patients with cardiovascular risk factors. The predictive value of reactive hyperemia for cardiovascular events in patients with atherosclerosis and the relative importance of reactive hyperemia compared with other measures of vascular function have not been previously studied. METHODS AND RESULTS: We prospectively measured reactive hyperemia and brachial artery flow-mediated dilation by ultrasound in 267 patients with peripheral arterial disease referred for vascular surgery (age 66+/-11 years, 26% female). Median follow-up was 309 days (range 1 to 730 days). Fifty patients (19%) had an event, including cardiac death (15), myocardial infarction (18), unstable angina (8), congestive heart failure (6), and nonhemorrhagic stroke (3). Patients with an event were older and had lower hyperemic flow velocity (75+/-39 versus 95+/-50 cm/s, P=0.009). Patients with an event also had lower flow-mediated dilation (4.5+/-3.0 versus 6.9+/-4.6%, P<0.001), and when these 2 measures of vascular function were included in the same Cox proportional hazards model, lower hyperemic flow (OR 2.7, 95% CI 1.2 to 5.9, P=0.018) and lower flow-mediated dilation (OR 4.2, 95% CI: 1.8 to 9.8, P=0.001) both predicted cardiovascular events while adjusting for other risk factors. CONCLUSIONS: Thus, lower reactive hyperemia is associated with increased cardiovascular risk in patients with peripheral arterial disease. Furthermore, flow-mediated dilation and reactive hyperemia incrementally relate to cardiovascular risk, although impaired flow-mediated dilation was the stronger predictor in this population. These findings further support the clinical relevance of vascular function measured in the microvasculature and conduit arteries in the upper extremity.

No gender influences on clinical outcomes or durability of repair following carotid angioplasty with stenting and carotid endarterectomy.

INTRODUCTION: To determine if gender influences clinical outcomes and durability of repair after carotid angioplasty with stenting (CAS) or carotid endarterectomy (CEA), an analysis of patient records was performed. METHODS: This study included 89 CAS patients (47 men and 42 women) and 93 CEA patients (53 men and 40 women). Patients underwent duplex scans 6, 12, 24 months post procedure. The outcomes of periprocedural mortality, major adverse events, strokes, and myocardial infarctions were assessed. Incidence of critical restenosis and recurrence of symptoms was also assessed. RESULTS: No significant differences were noted between men and women who had undergone either CAS or CEA (P > .05) for clinical outcomes and durability of repair. No differences for periprocedural mortality, major adverse events, critical restenosis, recurrent neurologic symptoms, and adverse event free survival were found. CONCLUSIONS: These results do not indicate substantial gender influences on clinical outcomes or durability of repair following CAS and CEA.

Mitogen-activated protein kinase p38 pathway in venous ulcer fibroblasts.

OBJECTIVE: Venous ulcer fibroblasts (w-fb) have attenuated growth compared to normal fibroblasts (n-fb). The MAPKp38 pathway mediates stress-responses in various diseases. We hypothesize that p38 pathway is altered in w-fb. METHODS: W-fb were isolated from venous ulcers and n-fb from the ipsilateral thigh. Fibroblasts were analyzed for phosphorylated p38 using immunoblot. The relation between p38 and w-fb proliferation was assessed with SB203580 (p38 inhibitor). Fibroblasts were treated with bFGF, TNF-a, and IL-1 and p38 expression analyzed. RESULTS: Phosphorylated p38 expression was increased in w-fb (AU%=233.5+/-59.7, P=0.039) compared to n-fb (AU%=99.9+/-14.6). W-fb treated with SB203580 demonstrated increased growth compared to untreated w-fb. W-fb treated with bFGF demonstrated decreased p38. TNF-alpha and IL-1beta significantly increase p38 expression. CONCLUSIONS: MAPK p38 is up-regulated in w-fb. Regulation of w-fb proliferation is influenced by p38. Altering the p38 pathway in vivo with growth factors or cytokine inhibition may improve fibroblast proliferation and venous ulcer healing.

Clinical impact of chronic renal insufficiency on endovascular aneurysm repair.

Endovascular aneurysm repair of abdominal aortic aneurysms has become a viable alternative to open repair. A significant proportion of this patient population has chronic renal insufficiency. The surgical outcomes associated with endovascular repair in 342 patients, with and without chronic renal insufficiency, are reported. Perioperative mortality, length of admission, length of intensive care unit admission, and rates of acute renal failure, congestive heart failure, myocardial infarction, conversion to open surgery, progression to hemodialysis, and incidence of endoleaks were retrospectively reviewed and analyzed. Endovascular repair demonstrated higher rates of acute renal failure, longer length of stay, and longer intensive care unit admissions in patients with chronic renal insufficiency. Patients with severe renal dysfunction demonstrated markedly elevated mortality and morbidity. These results indicate that chronic renal insufficiency is not an absolute contraindication to endovascular repair in patients with moderate renal dysfunction, but patients with severe renal dysfunction perform poorly after aortic reconstruction.

Mitogen-activated protein kinase pathway regulates cell proliferation in venous ulcer fibroblasts.

Venous ulcer fibroblasts have been demonstrated to have low growth rates in response to platelet-derived growth factor (PDGF). Mitogen-activated protein kinase (MAPK) is an important signal transduction mechanism that regulates growth, differentiation, and apoptosis in eukaryotic cells. PDGF binds PDGF receptors that activate a multitiered signaling cascade involving MAPK. We hypothesize that the growth regulation in venous ulcer fibroblasts is dependent on the MAPK extracellular signal-regulated kinase (ERK) pathway in the presence of PDGF. Fibroblasts (fb) were isolated from 8 patients with venous ulcers (w-fb) and the normal skin (n-fb) of the ipsilateral thigh via punch biopsies. Fb were plated at 1,500 cells/dish and treated with PDGF-AB (10 ng/mL) for 15 days. Growth rates were determined. Immunoblot analysis of MAPK ERK for n-fb and w-fb were analyzed. To determine if PDGF-stimulated w-fb and n-fb utilized the MAPK ERK pathway in a dependent manner, the upstream kinase MAPK kinase 1 (MEK 1) was inhibited by PD 98059. In addition, fb were treated with chronic venous ulcer wound fluid (WF) to study its effect on MAPK ERK. In the presence of PDGF, growth rates were substantially lower in w-fb than in n-fb, and MAPK was activated in 6/8 w-fb and in only 2/8 n-fb. Fibroblasts expressing MAPK had significantly reduced cell proliferation compared to fibroblasts not expressing MAPK (p = 0.023). PD 98059 significantly inhibited w-fb and n-fb cell proliferation from basal level, which was reversible with addition of PDGF. In neonatal fibroblasts WF demonstrated inhibition of MAPK ERK over time and addition of PD98059 was not additive. This study suggests that the MAPK ERK pathway is important for cell proliferation in venous ulcer fibroblasts. In the presence of PDGF, fibroblasts with decreased growth rate express MAPK, and proliferation is further abrogated with addition of MEK 1 inhibitor, suggesting the importance of the MAPK ERK pathway regulating w-fb and n-fb proliferation. Although the majority of w-fb activated the MAPK ERK pathway in the presence of PDGF, proliferation was significantly attenuated, indicating that other MAPK inhibitory pathways are competing. Venous ulcer wound fluid directly inhibits the MAPK ERK pathway, suggesting that the venous ulcer wound environment has negative trophic factors that effect fibroblasts proliferation and ulcer healing.

Risk stratification for postoperative cardiovascular events via noninvasive assessment of endothelial function: a prospective study.

BACKGROUND: Brachial artery endothelial function is impaired in individuals with atherosclerosis and coronary risk factors and improves with risk reduction therapy. However, the predictive value of brachial artery endothelial dysfunction for future cardiovascular events is unknown. METHODS AND RESULTS: We preoperatively examined brachial artery vasodilation using ultrasound in 187 patients undergoing vascular surgery. Patients were prospectively followed for 30 days after surgery. Forty-five patients had a postoperative event, including cardiac death (3), myocardial infarction (12), unstable angina/ischemic ventricular fibrillation (2), stroke (3), or elevated troponin I, reflecting myocardial necrosis (25). Preoperative endothelium-dependent flow-mediated dilation was significantly lower in patients with an event (4.9+/-3.1%) than in those without an event (7.3+/-5%; P<0.001), whereas endothelium-independent vasodilation to nitroglycerin was similar in both groups. In a Cox proportional-hazards model, the independent predictors of events were age (P=0.001), renal insufficiency (P=0.03), noncarotid surgery (P=0.05), and lower brachial artery flow-mediated dilation (P=0.007). If troponin I elevation was not considered an event, low flow-mediated dilation remained an independent predictor of risk (odds ratio 9.0, 95% CI 1.2 to 68; P=0.03). When a flow-mediated dilation cutpoint of 8.1% was used, endothelial function had a sensitivity of 95%, specificity of 37%, and negative predictive value of 98% for events. CONCLUSIONS: Impaired brachial artery endothelial function independently predicts postoperative cardiac events, which supports a role for endothelial dysfunction in the pathogenesis of cardiovascular disease. The strong negative predictive value of preserved endothelial function raises the possibility that assessment of brachial artery flow-mediated dilation will be useful in the management of patients undergoing vascular surgery.

Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease.

OBJECTIVES: The goal of this study was to prospectively examine the long-term predictive value of brachial-artery endothelial dysfunction for future cardiovascular events. BACKGROUND: Brachial-artery endothelial function is impaired in individuals with atherosclerosis and coronary risk factors. The prospective relation between endothelial function determined by brachial-artery ultrasound and long-term cardiovascular risk is unknown. METHODS: We examined brachial-artery endothelial function using ultrasound in 199 patients with peripheral arterial disease before elective vascular surgery. Patients were prospectively followed with an average follow-up of 1.2 years after surgery. RESULTS: Thirty-five patients had an event during follow-up, including cardiac death (5 patients), myocardial infarction (17 patients), unstable angina (10 patients), or stroke (3 patients). Preoperative endothelium-dependent flow-mediated dilation (FMD) was significantly lower in patients with an event (4.4 +/- 2.8%) compared with those without an event (7.0 +/- 4.9%, p < 0.001), whereas endothelium-independent vasodilation to nitroglycerin was similar in both groups. In a Cox proportional-hazards model, independent predictors of events included age (p = 0.003), more invasive surgery (surgery other than carotid endarterectomy, p = 0.02), and impaired brachial-artery endothelial function (p = 0.002). Risk was approximately nine-fold higher in patients with FMD <8.1% (lower two tertiles) compared with those in the upper tertile (odds ratio 9.5; 95% confidence interval 2.3 to 40). CONCLUSIONS: Impaired brachial-artery endothelial function independently predicts long-term cardiovascular events in patients with peripheral arterial disease. The findings suggest that noninvasive assessment of endothelial function using brachial-artery FMD may serve as a surrogate end point for cardiovascular risk.

Differences in risk factors for lower extremity arterial occlusive disease.

BACKGROUND: Patients undergoing lower extremity revascularization have associated cardiovascular risks: smoking, hypertension, dyslipidemia, and diabetes. This study evaluated the impact of cardiovascular risk factors on proximal versus distal arterial occlusive disease in patients undergoing lower extremity revascularization as adjusted to a control group without vascular disease. STUDY DESIGN: We performed a retrospective, case-control study that included 151 patients undergoing lower extremity revascularization and 229 patients undergoing knee and hip replacement (controls). Risk factors were determined for each of three separate groups undergoing revascularization for different levels of occlusive disease: aortoiliac, superficial femoral, and popliteal-tibial. Comparisons to controls were tested using t-tests or chi-square tests and multiple logistic regression. RESULTS: Dyslipidemia was associated with a significant risk of aortoiliac (odds ratio [OR]=3.4; p=0.0006) and superficial femoral occlusion (OR=2.8; p=0.01) but was less strongly associated with popliteal-tibial occlusion (OR=2.1; p=0.09). Smoking was strongly associated with aortoiliac (OR=4.5; p=0.004) and superficial femoral disease (OR=4.6; p=0.0007) but not popliteal-tibial disease (OR=1.3; p=0.53). In contrast, diabetes mellitus and chronic renal insufficiency were strong risk factors for popliteal-tibial occlusion (OR=5.4, p=0.0002; OR=3.9, p=0.01, respectively), but were not significant risk factors for aortoiliac or superficial femoral occlusion. CONCLUSIONS: These data, which use revascularization level as a surrogate marker for lower extremity arterial disease, suggest that the risk factor profile for proximal disease differs from that of distal disease. These findings may reflect differences in the biology of disease and indicate that different risk factors have various anatomic influences on arterial disease formation.

Bovine pericardium vs dacron for patch angioplasty after carotid endarterectomy: a prospective randomized study.

HYPOTHESIS: Bovine pericardium (BP) demonstrates improved intraoperative hemostasis and equivalent perioperative morbidity compared with Dacron when used as patch material for angioplasty following carotid endarterectomy. OBJECTIVE: To prospectively compare BP and Dacron patch angioplasty after carotid endarterectomy in a randomized fashion. METHODS: Ninety-five consecutive primary carotid endarterectomies were performed in a prospective randomized fashion in 92 patients. Fifty-one procedures were performed using BP and 44 using Dacron. Intraoperative suture line bleeding was subjectively evaluated by observing bleeding at 3 and 4 minutes following carotid cross-clamp removal and then objectively weighing the sponge used to tamponade bleeding during these time intervals. Perioperative morbidity, including cervical wound hematoma, transient ischemic attack, and stroke, and perioperative mortality were recorded. Statistical analysis was performed using paired t tests, chi(2) analysis, Fisher exact test, or multiple linear regression as appropriate. RESULTS: Suture line bleeding at 3 minutes was present in 7 (14%) of 51 patients in the BP group and 24 (55%) of 44 patients in the Dacron group (P<.001). Suture line bleeding evaluated at 4 minutes was present in 2 (4%) of 51 patients in the BP group and 13 (30%) of 44 patients in the Dacron group (P =.001). Net +/- SEM sponge weight (total intraoperative suture line bleeding) was 6.25 +/- 0.55 g in the BP group and 16.34 +/- 1.85 g in the Dacron group (P<.001). Total suture line bleeding was significantly affected by activated clotting time; however, multivariate analysis demonstrated that bleeding was significantly less with BP (P<.001) even after adjusting for differences in activated clotting time. CONCLUSIONS: Bovine pericardium demonstrated a statistically significant decrease in intraoperative suture line bleeding compared with Dacron. Handling characteristics were judged by the surgeons to be superior for BP. Therefore, we believe BP may be an alternative to Dacron when performing patch angioplasty of the carotid artery after endarterectomy.

Noninfectious saccular abdominal aortic aneurysm--a report of two cases.

Saccular aortic aneurysms are eccentrically shaped and are commonly thought to be the consequence of infection of the aorta. However, saccular-type aneurysms can be found independent of any clinical or subclinical infection and can be associated with a penetrating aortic ulcer. Moreover, penetrating aortic ulcers have been described in the thoracic aorta, but there is a paucity of any documentation of this clinical and pathologic entity occurring in the abdominal aorta. The authors describe 2 cases of symptomatic, penetrating atherosclerotic ulcers of the abdominal aorta causing saccular, noninfectious abdominal aortic aneurysms.

Acute thrombosis of abdominal aortic aneurysms--report of two cases and review of the literature.

An acutely thrombosed abdominal aortic aneurysm (AAA) is a rare but devastating complication of aortic aneurysms. Incidence in reported series is approximately 0.7-2.8% of surgically managed AAA cases with an associated mortality rate of 50%. To date there have been only 46 cases of acutely occluded AAAs reported in the literature. We present our experience of 2 additional cases of acute AAA thrombosis and discuss the mechanism of thrombosis and management. The size of the aneurysm seems to be a better predictor of rupture than of thrombosis. Strong risk factors for thrombosis are the presence of concomitant iliac artery and cardiac disease. Although this complication is rare, its high mortality rate makes it an important disease to understand, recognize, diagnose, and treat for a successful outcome.

Proliferative capacity of venous ulcer wound fibroblasts in the presence of platelet-derived growth factor.

Growth factors have been demonstrated to increase the proliferation of wound fibroblasts. Platelet-derived growth factor (PDGF) is a potent cell mitogen. However, the role of PDGF in chronic venous ulcers is inconclusive. This study investigated whether PDGF stimulates venous ulcer fibroblasts to proliferate. Fibroblasts (fb) were isolated from 8 venous ulcers wounds (w-fb) and normal skin (n-fb) of the ipsilateral thigh via punch biopsies. Fibroblasts were plated at 1,500 cells/dish in Dulbecco's Modified Eagle Medium + 10% calf serum (CM) and treated with/without PDGF-alphabeta (10 ng/mL) for 15 days. Growth rates were calculated. Western blotting and immunocytochemistry staining determined basal levels for PDGF-alpha and -beta receptors, respectively. Growth rates were significantly lower in w-fb than in n-fb (1,579 +/-546 vs 13,782 +/-5,882 cells/day, p=0.019). PDGF-alphabeta treatment caused n-fb to increase their proliferative capacity relative to complete media (20,393 +/-6,572 vs 13,782 +/-5,882 cells/day, p=0.005). However, PDGF-alphabeta had no significant effect on w-fb proliferation over CM (1,030 +/-264 and 1,579 +/-546 cells/day, p=0.15). In the presence of PDGF-alphabeta, w-fb had a significantly attenuated growth rate over n-fb (1,030 +/-264 vs 20,393 +/-6,572 cells/day, p=0.019). Western blot and immunocytochemistry analysis revealed diminished basal levels of PDGF-alpha and -beta receptors, respectively, in ulcer fibroblasts. Venous ulcer fibroblasts had decreased proliferation. PDGF-alphabeta had no effect on the growth rate of venous ulcer fibroblasts. In venous ulcers, decreased basal levels of fibroblast PDGF-alpha and -beta receptors may explain reduced proliferation. Further clinical studies are needed to elucidate the role growth factors may play in venous ulcers.

Obesity is not an independent risk factor for adverse perioperative and long-term clinical outcomes following open AAA repair or EVAR.

OBJECTIVES: Moderate (body mass index [BMI] ≥30) and morbid obesity (BMI ≥35) is increasing at an alarming rate in vascular surgery patients. The objective of this study was to determine the impact of obesity on perioperative and long-term clinical outcomes following open abdominal aortic aneurysm (AAA) repair or endovascular aneurysm repair (EVAR). METHODS: This review includes patients that underwent open AAA repair (n = 403) or EVAR (n = 223) from 1999 to 2009. Specific patient characteristics such as comorbid diseases, medications, and body mass index (BMI) were assessed. Specific perioperative outcomes such as length of stay, myocardial infarctions, and mortality were reviewed. In addition, long-term outcomes such as rates of reintervention, permanent renal dysfunction, and mortality beyond 30 days were also assessed. RESULTS: The incidence of obesity in open AAA patients was 25.3% (documented incidence 1.5%) and for EVAR was 24.6% (documented incidence 4%). Moderate and morbid obesity was associated with longer intensive care unit (ICU) admissions for both open AAA or EVAR patients (P < .05). However, no significant differences in perioperative outcomes in terms of overall length of stay, myocardial infarction, acute renal failure, wound infections, or mortality were noted between obese and nonobese patients underoing open AAA repair or EVAR (P > .05). Similarly, moderate and morbid obesity was not associated with significant differences in rates of reintervention, permanent renal dysfunction, and mortality beyond 30 days for patients undergoing open AAA repair or EVAR (P > .05). CONCLUSIONS: The results of this study indicate that moderate and morbid obesity are not independently associated with adverse perioperative and long-term clinical outcomes for patients undergoing open AAA repair or EVAR. Therefore, either open AAA repair or EVAR can be accomplished safely in moderately obese and morbidly obese patients.