Long term outcome for extra-anatomic arch reconstruction. An analysis of 143 procedures.

PURPOSE: With the FDA approval of thoracic endografts, extra-anatomic reconstruction of the aortic arch has allowed for more suitable proximal landing zones and increased applicability of thoracic endovascular procedures. We evaluated our short term and long term results of extra-anatomic reconstruction of the carotid and subclavian vessels. METHODS: One hundred and forty three (143) procedures were performed for extra-anatomic carotid and subclavian reconstruction. Of these 143 operations: 85 were carotid subclavian reconstructions, 22 were carotid crossover bypasses, 30 were subclavian carotid reconstructions and 6 were carotid subclavian transpositions. Sixty (42%) were male, 20 (14%) were diabetic, and 63 (44%) were current smokers. Mean age was 63 (SD +/- 12.3). Indication for surgery was primarily for occlusive or embolic disease (97%). In those patients undergoing bypass graft, prosthetic (ePTFE) was used in 93%. Follow-up was performed at 3 and 6 month intervals by ultrasound and pulse volume recordings where indicated. Life table analyses were used to analyze patency. RESULTS: Of the 143 reconstructions operative mortality was 1 (0.7%). Non-fatal complications included 3 (2.1%) for bleeding, 1 (0.7%) wound infection, 2 (1.4%) TIA, 1 (0.7%) suffered a non-fatal stroke, 2 (1.4%) had postoperative myocardial infarctions, and 6 (4.3%) late (>30-day) occlusions. Follow-up was 1 to 124 months (mean: 39 months). Primary patency at 1 year was 98%, 3 years 96%, and 5 years was 92%. CONCLUSION: Extra-anatomic arch reconstruction can be performed safely and appears to be durable over long term follow-up. Its use with endovascular grafting should provide a durable reconstruction for patients who require aortic "debranching" prior endovascular thoracic aortic aneurysm repair.

Relationship of proximal fixation to renal dysfunction in patients undergoing endovascular aneurysm repair.

Technological advancements have lead to dramatic improvements in stentgraft device design resulting in more trackable delivery systems and transrenal uncovered stents and barbs for better fixation. Transrenal bare-stents may limit stentgraft migration, particularly in patients with short or flared proximal aortic necks. However, potential disadvantages might be in worsening renal function, particularly in patients with preexisting renal insufficiency. We retrospectively analyzed our recent 7 year experience of patients undergoing endovascular aneurysm repair (EVAR) using a variety of stentgrafts with and without transrenal bare-stent fixation. Patients were divided into 2 groups; infrarenal fixation (IRF) vs transrenal fixation (TRF), or patients with preoperative serum Cr values that were normal (= or <1.5 mg/dl) vs slightly elevated (1.6-2 mg/dl), vs markedly elevated (2.1- 3.5 mg/dl). The exclusion criteria included patients with chronic renal insufficiency (CRI) on hemodialysis, and preoperative high-grade renal artery stenoses requiring angioplasty and stenting. Of 705 patients that underwent EVAR, 496 (IRF: 385 [78%], and TRF: 111 [22%]) were available with routine evaluations of serum Cr and CT scans. Preexisting comorbidities, mean procedure contrast volume, and postprocedure follow-up were similar in both groups. In the immediate postoperative period, mean serum Cr did not change significantly in either the IRF group (1.3+/-0.7 mg/dl to 1.2+/-0.9 mg/dl) or the TRF group (1.3+/-0.5 mg/dl to 1.3+/-0.6 mg/dl). Mean serum Cr did, however, significantly increase over longer follow-up in both groups: 1.4+/-0.8 mg/dl for IRF (P<0.03), and 1.5 +/- 0.8 mg/dl for TRF (P<0.01). Cr clearance was similarly unchanged in the immediate postoperative period (58+/-23 to 61+/-25 ml/min/1.73 m2 for IRF group, 53+/-17 to 55+/-17 ml/min/1.73 m2 for TRF group), but was significantly decreased in longer follow-up (53+/-23 ml/min/1.73 m2 for IRF, p<0.02: and 48+/-16 ml/min/1.73 m2 for TRF, P<0.01). There were no significant differences in serum Cr increase (p=0.19) or Cr clearance decrease (p=0.68) between the IRF and TRF groups. Small renal infarcts were noted in 6 patients (1.6%) in the IRF group, and in 8 patients (7%) in the TRF group (p=0.37). Of patients with normal preoperative renal function, renal dysfunction developed in 7.7% of IRF group and 6.1% of TRF group (p=0.76). In patients with preexisting CRI, renal dysfunction developed in 18.2% of IRF group, and 17.1% of TRF group (p=0.95). Eight patients with postoperative renal dysfunction, 5 (1.3%) from IRF group and 3 (2.7%) from TRF group subsequently required hemodialysis, and this difference was not statistically significant (p=0.91). We also analyzed 200 consecutive patients undergoing EVAR with intra-arterial contrast agents with and without preexisting CRI not on dialysis. The groups were identified on the basis of preprocedure serum Cr: group 1 (n=108), Cr less than 1.5 mg/dL (normal range); group 2 (n=65), Cr 1.5 to 2.0 mg/dL; group 3 (n=27), Cr 2.1 to 3.5 mg/dL. Routine precautions in patients with CRI included preoperative intravenous hydration with 2 L of normal saline solution, discontinuation of all nephrotoxic drugs, intraoperative administration of mannitol (0.5 g/kg intravenously), and use of nonionic, low osmolar intra-arterial contrast agent (Omnipaque 350). One-hundred and eight patients had normal renal function (group 1), and 92 patients had preexisting CRI with baseline Cr 1.5 to 2.0 mg/dL (group 2, n=65) or 2.1 to 3.5 mg/dL (group 3, n=27). Comorbid conditions included coronary artery disease (group 1, 51%; group 2, 49%; group 3, 59%), hypertension (group 1, 39%; group 2, 46%; group 3, 52%), and diabetes mellitus (group 1, 25%; group 2, 35%; group 3, 48%). In groups 1, 2, and 3, the mean volume of low osmolar contrast agent used was 210 cc, 160 cc, 130 cc, respectively; hemodynamic instability developed in 3, 1, and 1 patient, respectively. The incidence of postoperative complications between the 3 study groups was not statistically different. In grications between the 3 study groups was not statistically different. In group 1 a transient increase in serum Cr (>30% over baseline and >1.4 mg/dL) was noted in 3 patients (2.7%), 2 of whom (1.9%) required temporary hemodialysis and 1 (0.9%) who died of renal failure. In group 2 a transient increase in serum Cr was noted in 2 patients (3.1%); both patients (3.1%) required temporary hemodialysis, and 1 patient (1.5%) died of renal failure. In group 3 a transient increase in serum Cr was noted in 2 patients (7.4%); 1 patient (3.7%) required temporary hemodialysis, and 1 patient (3.7%) died of renal failure. Perioperative hypotension significantly increased the risk for elevated serum Cr and death (p<0.05), and larger contrast volume was associated with an increase in serum Cr (p<0.05) during the postoperative period. Following EVAR renal function declines slightly with both IRF and TRF. Our data show no overall difference between patients with IRF and TRF with respect to infarcts, decline in renal function, or onset of dialysis. There were a slightly greater number of renal infarcts in the TRF group, but these infarcts were clinically inconsequential. In patients with CRI, EVAR with intra-arterial radiographic contrast agents is believed to impair renal function, and CRI is considered a relative contraindication to the procedure. Results of our investigation indicate that risk for worsening renal insufficiency, dialysis, and death is only slightly and not significantly greater in patients with CRI compared with patients with normal renal function. With appropriate precautions of avoiding perioperative hypotension and limiting the volume of nonionic contrast agents, CRI need not be a contraindication for EVAR with intra-arterial contrast agents.

The multidisciplinary approach to prevention and treatment of cardiovascular disease: creation of a vascular care network.

Vascular care, diagnosis, and intervention can be very complex. Multiple specialists commonly are involved in dealing with patients with systemic atherosclerotic disease. Although each specialist may provide state-of-the-art care with good result, it would be advantageous to minimize duplication of effort and thereby improve cost efficiency. Patients still could reap the benefit of all these disciplines if evaluated for their vascular complaint in a coordinated system. In doing so, atherosclerosis prevention with risk factor modification, as well as diagnosis and therapy for the presenting problem all can be simultaneously managed. This is the concept that has motivated groups such as our own to form a comprehensive vascular center. We describe our experience with establishing a vascular center and outline its benefits and limitations.

Immunoreactivity of adventitial matrix fibrils of normal and aneurysmal abdominal aorta with antibodies against vitronectin and fibrinogen.

PURPOSE: We have reported that immunoglobulin G (IgG) harvested from specimens of aneurysmal abdominal aorta (AAA) is immunoreactive with a fibrillar component of the matrix of the aortic adventitia. In further studies we have reported the partial amino acid sequence of a 40-kDa protein, purified from the adventitia of the human aorta, which we have called aortic aneurysm antigenic protein-40 kDa (AAAP-40). AAAP-40 has homologies with bovine microfibril-associated glycoprotein-36 kDa (MAGP-36). Both AAAP-40 and MAGP-36 have homologies to fibrinogen beta (FB-b) and vitronectin (VN). The purposes of the present experiments were (1) to determine whether antibodies against VN and fibrinogen are immunoreactive with elements of the normal and/or aneurysmal aortic wall, and (2) to determine whether these antibodies are immunoreactive with soluble extracts of aortic proteins. METHODS: Paraffin-embedded tissue sections of normal and aneurysmal aorta were probed with polyclonal rabbit antihuman VN and antihuman FB-b antibodies. Immunoblots of soluble aortic proteins were evaluated with the same antibodies. Histochemical preparations with Gomori's aldehyde fuchsin and elastin-von-Gieson solutions were also performed. RESULTS: Anti-VN and FB-b antibodies reacted with matrix fibrils in the aortic adventitia in both normal and aneurysmal specimens, with a distribution that resembles the appearance of fibrils that are stained by Gomori's reaction. By comparison to normal adventitial fibrils, fibrils in the specimens from AAA appeared fragmented, coiled, and frayed. Antibodies against VN and FB-b were immunoreactive in immunoblots with a soluble aortic protein of molecular weight approximately 40 kDa, consistent with the migration of AAAP-40. CONCLUSIONS: There appear to be immunodeterminants in AAAP-40 that are recognized by polyclonal antibodies against VN and FB-b.

Molecular cloning of the complementary DNA for an additional member of the family of aortic aneurysm antigenic proteins.

PURPOSE: We have purified and partially sequenced a protein from the adventitia of the human aorta (aortic aneurysm antigenic protein 40 kDa; AAAP-40) that has homologies to bovine aortic microfibril-associated glycoprotein (MAGP-36). It is immunoreactive with immunoglobulin G (IgGs) purified from the serum and aortic wall of patients with abdominal aortic aneurysms. AAAP-40 and MAGP-36 have fibrinogen-like and vitronectin-like motifs. Screening an expression library constructed from human aortic adventitial messenger RNA has resulted in the cloning of three complementary DNAs whose gene products are immunoreactive with immunoglobulin G from patients with abdominal aortic aneurysms. Two strongly resemble each other and have been described separately. The purpose of this article is to report the third clone. METHODS: Messenger RNA from a specimen of human aortic aneurysmal adventitia was reverse-transcribed for insertion into the phagemid Uni Zap XR (Stratagene). A strain of Escherichia coli, engineered for expression (XL 1-Blue MFR', Stratagene), was transfected, and rabbit antihuman vitronectin antibody as used to identify positive clones. Sequencing of the positive clones was performed by the Core Laboratories at Columbia University. RESULTS: The hypothetical protein of rAAAP-CL4 (clone 4) shares sequence motifs with known microfibril-associated glycoproteins (MAGPs). The recombinant protein (rAAAP-CL4) is immunoreactive with serum from patients (three of four abdominal aortic aneurysm sera). In addition, similarities have been detected with immunoglobulins of the kappa family and with a protein from cytomegalovirus that is a potential molecular mimic. CONCLUSIONS: There may several members of a novel family of human aortic autoantigenic proteins implicated in abdominal aortic aneurysm disease.

Expression of two novel recombinant proteins from aortic adventitia (kappafibs) sharing amino acid sequences with cytomegalovirus.

We have recently purified and partially sequenced a microfibrillar protein from human aortic adventitia (aneurysm-associated antigenic protein, 40 kDa [AAAP-40]) that is immunoreactive with immunoglobulin (IgG) from the wall of abdominal aortic aneurysms (AAAs). It shares motifs with Ig kappa (which may act as a binding site for interaction with integrins), cytomegalovirus (which may be a molecular mimic in the pathogenesis of AAA), and vitronectin and the fibrinogens. A cDNA library was constructed from the aortic adventitia of a AAA. The library was screened with either rabbit anti-vitronectin antibody or rabbit anti-fibrinogen antibody. Positive plaques were purified and expressed in a strain of Escherichia coli. The clone sequences were analyzed. The expressed proteins were separated by SDS/PAGE and the immunoblots were probed with either AAA IgG or anti-human Ig kappa antibody. Experimental cell lines, transfected with the clones (clones 1 and 5), synthesized recombinant proteins (rAAAP-CL1 and rAAAP-CL5), detectable in Western immunoblots with AAA IgG. A prediction of the tertiary structure resembles well-characterized cell adhesion molecules. These findings suggest that there is a novel family of matrix proteins that may use immunoglobulin motifs as binding sites for cellular integrins and that there are matrix proteins in addition to AAAP-40 that may serve as autoantigens in the pathogenesis of AAA disease.

Three-dimensional modeling and molecular evolution of Matrix Cell Adhesion Molecule #2: MAT-CAM 2.

Our research group has recently reported the partial amino acid sequence of an aortic adventitial collagen-associated fibrillar protein, which may be the target of an autoimmune response in patients with abdommal aortic aneurysms (AAA). Its apparent molecular weight is approximately 40 kDa, so we have named it aneurysm-associated antigenic protein-40 kDa (AAAP-40). It has similarities to microfibril-associated glycoprotein-36 kDa (MAGP-36), which was reported by Kobayashi et al. to have a tissue distribution limited to the aorta in pig; unlike other microfibrillar proteins which appear to distribute ubiquitously throughout the body with elastin. Accordingly, if AAAP-40 is the human homolog of MAGP-36, it would explain how an autoimmune reaction against this protein might have consequences more or less limited to the aorta and its branches.

A novel hypothesis to explain the hemorrhagic and connective tissue manifestations of Ebola virus infection.

The hemorrhagic and connective tissue complications of infection with Ebola virus are poorly understood. While searching for homologies and motifs of the aortic aneurysm-associated autoantigenic protein 40 kDa (AAAP-40), we have noted some short sequences (possibly shared epitopes) that occur in the envelope glycoprotein (40 kDa) of the Ebola virus. As a first step toward determining whether molecular mimicry of human matrix proteins by the Ebola virus protein might explain some of the severe connective tissue manifestations of infection, we have tested whether immunoglobulin (IgG) purified from the sera of patients with abdominal aortic aneurysm (AAA) are immunoreactive with the 40-kDa protein of the Ebola virus. Immunoblots of soluble Ebola proteins (strain Mayinga/Zaire) were probed with IgG's purified from the sera of eight patients with AAA and two healthy young control volunteers. The proteins were also probed with IgG extracted from the walls of two surgical aneurysm specimens. Serum IgG from eight consecutively studied AAA patients was immunoreactive with an Ebola virus protein of 40 kDa, consistent with the envelope glycoprotein. IgG's extracted from the walls of two AAAs were also reactive. The control sera were not reactive. In addition to the Ebola sequences in AAAP-40, an Ebola sequence also occurs in the microfibril-associated glycoprotein-4 (MAGP-4), which is distributed ubiquitously throughout connective tissue with elastin. We hypothesize that the catastrophic hemorrhagic and connective tissue complications of Ebola virus infection may be the result of these shared epitopes.

Two hypothetical proteins of human aortic adventitia, with Ig kappa, collagenous, and aromatic-rich motifs.

Two of five clones, selected from an expression library of aortic adventitia, encode unique hypothetical proteins sharing sequences of Ig kappa, gly/pro rich (collagenous) motifs, and aromatic motifs that occur in several proteins of the extracellular matrix. Both proteins have a similar domain structure with at least 8 regions: (1) Ig kappa (84-120 residues in length); (2) ser/thr-rich motif (44-63); (3) a second Ig kappa motif (9-12); (4) either a possible calcium-binding motif or a gly/pro rich sequence (35-43); (5) an aromatic rich sequence (6-7); (6) another gly/pro rich sequence (62-72); (7) a third Ig kappa sequence (26-28); and (8) a C-terminal 68-70 residue sequence with another aromatic motif.