Faculty Bibliography

OBJECTIVES/OBJECTIVE:To examine the relationship between the orientation of the iliac arteries in infrarenal aortic aneurysms and its effect on the cannulation of the contralateral limb of a bifurcated stent graft system (SGS) used for endovascular aneurysm repair (EVAR). METHODS:This is a retrospective review of prospectively collected data in 100 consecutive patients treated with EVAR using the Zenith device (Cook Medical Inc., Bloomington, Indiana, USA). We collected data on reciprocal orientation between the origins of the common iliac arteries (OOCIA) on an axial plane, the common femoral artery (right or left) used to deliver the main body of the SGS (access side), and the cannulation time of the contralateral limb. The latter was defined as the time elapsed between the introduction of the selective catheter in the contralateral iliac artery to the time of successful cannulation of the contralateral limb of the SGS. Using an Aquarius workstation (v. 3.5; TeraRecon Inc, San Mateo, Calif), the OOCIA was measured establishing the center of the origin of the right and left common iliac arteries and joining them using a straight line. A horizontal line was then drawn through the origin of the right common iliac artery. The angle created by these two lines was defined as "zero," "positive," or "negative." We examined the relations between cannulation time, access side, and OOCIA using t tests and a multivariate regression analysis. RESULTS:In 84 patients, the origin of the right common iliac artery was in an anterior position compared with the left; in 16, the origin of the right and left were on the same horizontal line; and the right common iliac artery was posterior in none of the patients. The main body of the prosthesis was delivered using the left femoral artery in 52 patients and the right in 48. When all patients were considered, cannulation time was shorter when the main body of the bifurcated prosthesis was delivered through the left femoral artery (9.3 +/- 5.8 minutes vs 15.4 +/- 7.2 minutes, P < .0001). This effect was more pronounced when only patients with the left common iliac artery located posteriorly were examined (9.3 +/- 5.80 minutes vs 16.4 +/- 7.6 minutes, P < .0001). There was no correlation between increasing negativity of the OOCIA angle and cannulation time, regardless of access side. CONCLUSION/CONCLUSIONS:We have shown that in patients with infrarenal aortic aneurysms, the origin of the right iliac artery is often anterior compared with the left and that cannulation time of the contralateral limb is shorter when the main body of the prosthesis is delivered from the left.

UNLABELLED:Acute coronary syndrome (ACS) guidelines recommend that most patients receive dual antiplatelet therapy with clopidogrel and acetylsalicylic acid (ASA) at the time of presentation to prevent recurrent ischemic events. Approximately 10% of ACS patients require coronary artery bypass grafting surgery (CABG) during the index admission. Most studies show that patients who receive ASA and clopidogrel within five days of CABG have an increase in operative bleeding. Current consensus guidelines recommend discontinuation of clopidogrel therapy at least five days before planned CABG to reduce bleeding-related events. However, high-risk individuals may require urgent surgery without delay, to reduce the risk of potentially fatal ischemic events. The present multidisciplinary position statement provides evidence- based recommendations for the optimal use of dual antiplatelet therapy to balance ischemic and bleeding risks in patients with recent ACS who may require urgent CABG. RECOMMENDATIONS/CONCLUSIONS:1. All ACS patients should be considered for dual antiplatelet therapy with ASA and clopidogrel at the earliest opportunity, despite the possibility of a need for urgent CABG. 2. For patients who have received clopidogrel and ASA, and require CABG: * Those at high risk of an early fatal event (eg, with refractory ischemia despite optimal medical treatment, and with high-risk coronary anatomy (eg, severe left main stenosis with severe right coronary artery disease), should be considered for early surgery without discontinuation of clopidogrel. * In patients with a high bleeding risk (eg, previous surgery, complex surgery) who are also at high risk for an ischemic event, consideration should be given to discontinuing clopidogrel for three to five days before surgery. * Patients at a lower risk for ischemic events (most patients) should have clopidogrel discontinued five days before surgery. 3. For patients who have CABG within five days of receiving clopidogrel and ASA, the risk of major bleeding and transfusion can be minimized by applying multiple strategies before and during surgery. 4. Patients who receive clopidogrel pre-CABG for a recent ACS indication should have clopidogrel restarted after surgery to decrease the risk of recurrent ACS. 5. For patients with a recent coronary stent, the decision to continue clopidogrel until the time of surgery or to discontinue will depend on the risk and potential impact of stent thrombosis. Restarting clopidogrel after CABG will depend on whether the stented vessel was revascularized, the type of stent and the time from stent implantation. Clopidogrel should be restarted when hemostasis is assured to prevent recurrent acute ischemic events.

OBJECTIVES/OBJECTIVE:Aorto-iliac angulations may be challenging for modular stent-graft systems (SGSs) from a single manufacturer. This study aims to define the pullout forces (POFs) of SGSs derived from the same (non-hybrid) or different manufacturers (hybrid). METHODS:The POFs were tested in a vertical position in air and 5% albumin. We studied the POFs between legs from Anaconda (Vascutek), Excluder (Gore), Talent (Medtronic) and Zenith (Cook) with the contralateral limb of bifurcated aortic bodies from Zenith (12 mm), Anaconda and Excluder. RESULTS:For non-hybrid SGSs, the POFs decreased in the following order: Anaconda (11.2+/-0.6N), Talent (6.25+/-0.6N), Zenith (3.5+/-0.01 N) and Excluder (2.5+/-0.5 N). The Zenith body with the Anaconda limb (15 mm) registered the greatest POF (13.083+/-0.821 N); the Zenith and Excluder bodies combined with the Excluder limb (16 mm) registered the weakest POFs (2.397+/-0.22 N and 2.500+/-0.479 N, respectively). The Zenith body combined with the Excluder limb (16 mm) had a POF similar to the Zenith non-hybrid; combined with Talent 14 mm and Anaconda limb exhibited POFs greater than the Zenith non-hybrid system. For the limb-to-limb POFs, the greatest was registered for the Anaconda limb, 13 mm within a 12-mm extension for 40-mm overlaps (23.06+/-0.480 N); the weakest POFs were recorded for the Excluder limbs at 30-mm overlaps (1.09+/-0.167 N and 1.11+/-0.250 N). CONCLUSIONS:The hybrid SGSs performed as well as or better than the non-hybrid systems, and should be considered for clinical testing in patients whose unique anatomy warrants the flexibility that the use of hybrids provides.

Improving endothelial nitric oxide synthase (eNOS) bioactivity and endothelial function is important to limit native, vein graft, and transplant atherosclerosis. Visfatin, a NAD biosynthetic enzyme, regulates the activity of the cellular survival factor, Sirt1. We hypothesized that visfatin may improve eNOS expression, endothelial function, and postnatal angiogenesis. In human umbilical vein (HUVEC) and coronary artery endothelial cells, we evaluated the effects of recombinant human visfatin on eNOS protein and transcript expression and mRNA stability, in the presence and absence of visfatin RNA silencing. We also assessed visfatin-induced protein kinase B (Akt) activation and its association with src-tyrosine kinases, phosphorylation of Ser(1177) within eNOS in the presence and absence of phosphatidylinositol 3-kinase (PI 3-kinase) inhibition with LY-294002, and evaluated the contributory role of extracellular signal-regulated kinase 1/2. Finally, we determined the impact of visfatin on HUVEC migration, proliferation, inflammation-induced permeability, and in vivo angiogenesis. Visfatin (100 ng/ml) upregulated and stabilized eNOS mRNA and increased the production of nitric oxide and cGMP. Visfatin-treated HUVEC demonstrated greater proliferation, migration, and capillary-like tube formation but less tumor necrosis factor-alpha-induced permeability; these effects were decreased in visfatin gene-silenced cells. Visfatin increased total Akt and Ser(473)-phospho-Akt expression with concomitant rises in eNOS phosphorylation at Ser(1177); these effects were blocked by LY-2940002. Studies with PP2 showed that the nonreceptor tyrosine kinase, src, is an upstream stimulator of the PI 3-kinase-Akt pathway. Visfatin also activated mitogen-activated protein (MAP) kinase through PI 3-kinase, and mitogen/extracellular signal-regulated kinase inhibition attenuated visfatin-elicited Akt and eNOS phosphorylation. Visfatin-filled Matrigel implants showed an elevated number of infiltrating vessels, and visfatin treatment produced significant recovery of limb perfusion following hindlimb ischemia. These results indicate a novel effect of visfatin to stimulate eNOS expression and function in endothelial cells, via a common upstream, src-mediated signaling cascade, which leads to activation of Akt and MAP kinases. Visfatin represents a translational target to limit endothelial dysfunction, native, vein graft and transplant atherosclerosis, and improve postnatal angiogenesis.

OBJECTIVE:Increasing experience with thoracic aortic stent grafts has led to a more aggressive approach to thoracic aortic pathologies in the distal aortic arch and proximal descending thoracic aorta. To increase the length of the proximal landing zone, it is sometimes necessary to cover the left subclavian artery with the thoracic stent-graft, introducing the risk of retrograde filling of the excluded aorta from the left subclavian artery. It is currently unclear how best to manage these patients to prevent persistent risk of aneurysm expansion or rupture. We report our experience with a minimally invasive endovascular repair of the covered left subclavian artery. METHODS:We reviewed prospectively gathered data on all investigational device exemption-approved patients undergoing thoracic aortic stent grafting at the Arizona Heart Institute from 2000 to 2006 (n = 289 patients). Patients had surveillance with a contrast-enhanced computed tomography scan on the first postoperative day and during follow-up at 1, 6, and 12 months. RESULTS:A total of 289 patients received thoracic stent grafts during the study: Medtronic Talent (Medtronic, Minneapolis, Minn) (n = 25) or Gore TAG (WL Gore & Associates Inc, Flagstaff, Ariz) (n = 261). The left subclavian artery was covered in 23% of patients (n = 66), of whom 17% had preoperative carotid-subclavian bypass (n = 11/66). Among patients with left subclavian artery coverage, the 30-day mortality was 6.1% (n = 4), procedure-related strokes developed in 3 patients (n = 3, 4.6%), and the incidence of left arm claudication was 7.6% (n = 5), necessitating postoperative carotid-subclavian bypass in 2 patients. Twelve patients (18%) had a type I (n = 6) or II (n = 7) endoleak. Coverage of the left subclavian artery accounted for 71% of the type II endoleaks (n = 5), whereas patent intercostals accounted for the rest (n = 2). Type II endoleaks associated with left subclavian artery coverage were successfully treated by retrograde coil embolization from the left brachial artery (n = 3) or left subclavian artery ligation (n = 1). CONCLUSION/CONCLUSIONS:Coverage of the left subclavian artery during thoracic aortic stent grafting is associated with a low incidence of arm complications and type II endoleaks. All type II endoleaks were successfully treated by retrograde coil embolization or ligation of the left subclavian artery. Successful treatment of endoleaks may reduce the risk of aneurysm expansion or rupture.

The endothelium plays a central role in the maintenance of vascular homeostasis. One of the main effectors of endothelial dysfunction is ANG II, and pharmacological approaches to limit ANG II bioactivity remain the cornerstone of cardiovascular therapeutics. Angiotensin converting enzyme-2 (ACE2) has been identified as a critical negative modulator of ANG II bioactivity, counterbalancing the effects of ACE in determining net tissue ANG II levels; however, the role of ACE2 in the vasculature remains unknown. In the present study, we hypothesized that ACE2 is a novel target to limit endothelial dysfunction and atherosclerosis. To this aim, we performed in vitro gain and loss of function experiments in endothelial cells and evaluated in vivo angiogenesis and atherosclerosis in apolipoprotein E-knockout mice treated with AdACE2. ACE2-deficient mice exhibited impaired endothelium-dependent relaxation. Overexpression of ACE2 in human endothelial cells stimulated endothelial cell migration and tube formation, and limited monocyte and cellular adhesion molecule expression; effects that were reversed in ACE2 gene silenced and endothelial cells isolated from ACE2-deficient animals. ACE2 attenuated ANG II-induced reactive oxygen species production in part through decreasing the expression of p22phox. The effects of ACE2 on endothelial activation were attenuated by pharmacological blockade of ANG-(1-7) with A779. ACE2 promoted capillary formation and neovessel maturation in vivo and reduced atherosclerosis in apolipoprotein E-knockout mice These data indicate that ACE2, in an ANG-(1-7)-dependent fashion, functions to improve endothelial homeostasis via a mechanism that may involve attenuation of NADPHox-induced reactive oxygen species production. ACE2-based treatment approaches may be a novel approach to limit aberrant vascular responses and atherothrombosis.

Sepsis is a multifactorial, and often fatal, disorder typically characterized by widespread inflammation and immune activation with resultant endothelial activation. In the present study, we postulated that the adipokine adiponectin serves as a critical modulator of survival and endothelial activation in sepsis. To this aim, we evaluated both loss-of-function (adiponectin gene-deficient mice) and subsequent gain-of-function (recombinant adiponectin reconstitution) strategies in two well-established inflammatory models, cecal ligation perforation (CLP) and thioglyocollate-induced peritonitis. Adipoq(-/-) mice, subjected to CLP, exhibited a profound ( approximately 8-fold) reduction in survival compared with their wild-type Adipoq(+/+) littermates after 48 h. Furthermore, compared with wild-type controls, thioglycollate challenge resulted in a markedly greater influx of peritoneal neutrophils in Adipoq(-/-) mice accompanied by an excess production of key chemoattractant cytokines (IL-12p70, TNFalpha, MCP-1, and IL-6) and upregulation of aortic endothelial adhesion molecule VCAM-1 and ICAM-1 expressions. Importantly, all of these effects were blunted by recombinant total adiponectin administration given 3 days prior to thioglycollate challenge. The protective effects of adiponectin were ascribed largely to higher-order adiponectin oligomers, since administration of recombinant C39A trimeric adiponectin did not attenuate endothelial adhesion molecule expression in thioglycollate-challenged Adipoq(-/-) mice. These data suggest a critical role of adiponectin as a modulator of survival and endothelial inflammation in experimental sepsis and a potential mechanistic link between adiposity and increased sepsis.

Repair of thoracic arch aneurysms in the octogenarian is associated with a high morbidity and mortality. In this report we describe a minimally invasive approach to repair and arch aneurysm using an endoluminal graft with an extrathoracic, extra anatomic de-branching of the arch vessels. The advantage of this technique includes avoidance of a median sternotomy, cardiopulmonary bypass, and circulatory arrest with a rapid postoperative recovery.

BACKGROUND:Enlargement of the aortic annulus during aortic valve replacement permits insertion of a larger prosthetic valve. Previous reports suggest patch enlargement of the aortic annulus increases operative morbidity and mortality during aortic valve replacement. We compared outcomes for this procedure in a contemporary group of patients with those operated on during an earlier era, to determine whether aortic annular enlargement is still associated with worse outcomes. METHODS:We reviewed prospectively gathered data on all patients undergoing aortic valve replacement and aortic annular enlargement at our institution from 1995 to 2005 (n = 669). We compared patient outcomes from two consecutive time periods: 1995 through 2000 (n = 360) versus 2001 through 2005 (n = 309). Propensity matching adjusted for baseline differences in a secondary analysis. RESULTS:Operative mortality was significantly lower in the more recent surgical group (2.9% versus 7.2%; p = 0.013). The rates of perioperative myocardial infarction (1.9% versus 1.1%; p = 0.4), stroke (2.9% versus 3.3%; p = 0.8), and pacemaker implantation (9.1% versus 12.5%; p = 0.16) were similar for both groups (2001 through 2005 versus 1995 through 2000, respectively). The earlier group of patients had a higher prevalence of congestive heart failure, syncope, angina, New York Heart Association class III or IV symptoms, chronic obstructive pulmonary disease, mitral valve disease, and previous cardiac surgery. After adjusting for these baseline differences with propensity matching, the risk of perioperative death remained lower in the contemporary group (3% versus 7.5%; p = 0.04). CONCLUSIONS:Enlargement of the aortic annulus in the modern era is a safe adjunct to aortic valve replacement, and should be considered in selected patients to avoid patient-prosthesis mismatch.