Multicenter Study on Physician-Modified Endografts for Thoracoabdominal and Complex Abdominal Aortic Aneurysm Repair.

BACKGROUND: Physician modified endografts (PMEGs) have been widely used in the treatment of complex abdominal aortic aneurysm and thoracoabdominal aortic aneurysm, however, previous data are limited to small single center studies and robust data on safety and effectiveness of PMEGs are lacking. We aimed to perform an international multicenter study analyzing the outcomes of PMEGs in complex abdominal aortic aneurysms and thoracoabdominal aortic aneurysms. METHODS: An international multicenter single-arm cohort study was performed analyzing the outcomes of PMEGs in the treatment of elective, symptomatic, and ruptured complex abdominal aortic aneurysms and thoracoabdominal aortic aneurysms. Variables and outcomes were defined according to the Society for Vascular Surgery reporting standards. Device modification and procedure details were collected and analyzed. Efficacy outcomes included technical success and safety outcomes included major adverse events and 30-day mortality. Follow-up outcomes included reinterventions, endoleaks, target vessel patency rates and overall and aortic-related mortality. Multivariable analysis was performed aiming at identifying predictors of technical success, 30-day mortality, and major adverse events. RESULTS: Overall, 1274 patients were included in the study from 19 centers. Median age was 74 (IQR, 68-79), and 75.7% were men; 45.7% were complex abdominal aortic aneurysms, and 54.3% were thoracoabdominal aortic aneurysms; 65.5% patients presented electively, 24.6% were symptomatic, and 9.9% were ruptured. Most patients (83.1%) were submitted to a fenestrated repair, 3.6% to branched repair, and 13.4% to a combined fenestrated and branched repair. Most patients (85.8%) had ≥3 target vessels included. The overall technical success was 94% (94% in elective, 93.4% in symptomatic, and 95.1% in ruptured cases). Thirty-day mortality was 5.8% (4.1% in elective, 7.6% in symptomatic, and 12.7% in ruptured aneurysms). Major adverse events occurred in 25.2% of cases (23.1% in elective, 27.8% in symptomatic, and 30.3% in ruptured aneurysms). Median follow-up was 21 months (5.6-50.6). Freedom from reintervention was 73.8%, 61.8%, and 51.4% at 1, 3, and 5 years; primary target vessel patency was 96.9%, 93.6%, and 90.3%. Overall survival and freedom from aortic-related mortality was 82.4%/92.9%, 69.9%/91.6%, and 55.0%/89.1% at 1, 3, and 5 years. CONCLUSIONS: PMEGs were a safe and effective treatment option for elective, symptomatic, and ruptured complex aortic aneurysms. Long-term data and future prospective studies are needed for more robust and detailed analysis.

Distal Repair After Total Aortic Arch Replacement With Frozen Elephant Trunk in Patients With Chronic Multilevel Thoracic Aortic Disease.

OBJECTIVE: To examine the management of distal aortic disease after total arch replacement with the frozen elephant trunk (TAR + FET) in patients with chronic thoracic aortic disease. METHODS: Two centre retrospective study of consecutive patients treated between January 2010 and December 2019. The primary endpoint was 30 day or in hospital death. The secondary endpoint was midterm survival. Data are presented as median (interquartile range [IQR]). The χ2 or Fisher's exact test was used as appropriate. Estimated survival (standard error) was assessed by calculating the Kaplan-Meier product limit estimator with right censoring of survival data. A p value of < .050 was considered statistically significant. STROBE guidelines were followed. RESULTS: A total of 158 patients (72 men; median age 70 years, IQR 64, 75; median distal aortic diameter 58 mm, IQR 46, 68; 127 aneurysmal disease, 31 chronic dissection) underwent TAR + FET. The peri-operative mortality rate was 10.1% (9/107 elective, 7/51 non-elective). Of 74 (46.8%) patients with a primary distal seal, seven (9.5%) died peri-operatively, the distal seal was maintained during follow up in 51, nine underwent late distal repair (two planned, seven unplanned; one open, eight endovascular; one peri-operative death) with a median interval to unplanned repair of 777 days (IQR 462, 1480), and seven with loss of seal had no intervention. Distal seal failed in 2/28 (7%) patients with a distal seal length > 30 mm and device oversizing > 10%, compared with 12/39 (31%) patients who did not meet these criteria (p = .031). In 84 patients without a primary distal seal, nine (10.7%) died peri-operatively, the distal aorta remained below the size threshold for repair during follow up in 12 patients, 44 had distal repair (median aortic diameter 64 mm, IQR 60, 75; eight open, one hybrid, 35 endovascular repairs; no deaths) at a median of 256 days (IQR 135, 740), and 19 did not have distal repair at the end of the follow up period: six died before planned repair at a median interval of 115 days (IQR 85, 120); eight were considered unfit; one was assessed as fit but declined; and four patients were awaiting assessment. Median follow up was 46 months (IQR 26, 75): no patients were lost to follow up. Estimated ± standard error five year survival was 61.5 ± 4.1%: elective 70.6 ± 4.7%, non-elective 43.2 ± 7.2%. CONCLUSION: TAR + FET achieved primary distal seal in 47% of patients, but late failure occurred in 21%. Distal repair was ultimately indicated in 84% of survivors without a primary distal seal and of these 70% underwent repair, almost 10% died before planned repair, and 13% were considered unfit. Earlier distal endovascular repair and better assessment of patient fitness may improve midterm outcomes.

The Complementary Roles of Open and Endovascular Repair of Extent I - III Thoraco-abdominal Aortic Aneurysms in a United Kingdom Aortic Centre.

OBJECTIVE: A multidisciplinary approach offering both open surgical repair (OSR) and complex endovascular aortic repair (cEVAR) is essential if patients with thoraco-abdominal aortic aneurysms (TAAAs) are to receive optimal care. This study reports early and midterm outcomes of elective and non-elective OSR and cEVAR for extent I - III TAAA in a UK aortic centre. METHODS: Retrospective study of consecutive patients treated between January 2009 and December 2021. Primary endpoint was 30 day/in hospital mortality. Secondary endpoint was Kaplan-Meier estimates of midterm survival. Data are presented as median (interquartile range [IQR]). RESULTS: In total, 296 patients (176 men; median age 71 years [IQR 65, 76]; median aneurysm diameter 66 mm [IQR 61, 75]) underwent repair (222 elective, 74 non-elective). OSR patients (n = 66) were significantly younger with a higher incidence of heritable disease and chronic dissection, while cEVAR patients (n = 230) had a significantly higher prevalence of coronary, pulmonary, and renal disease. Overall, in hospital mortality after elective and non-elective repair was 3.2% (n = 7) and 23.0% (n = 17), respectively, with no significant difference between treatment modalities (elective OSR 6.5% vs. cEVAR 2.3%, p = .14; non-elective OSR 25.0% vs. cEVAR 20.3%, p = .80). Major non-fatal complications occurred in 15.3% (33/215) after elective repair (OSR 39.5%, 17/43, vs. cEVAR 9.3%, 16/172; p < .001) and 14% (8/57) after non-elective repair (OSR 26.7%, 4/15, vs. cEVAR 9.5%, 4/42; p = .19). Median follow up was 52 months (IQR 23, 78). Estimated survival ± standard error at 1, 3, and 5 years for the entire cohort was 89.6 ± 2.0%, 76.6 ± 2.9%, and 69.0% ± 3.2% after elective repair, and 67.6 ± 5.4%, 52.1 ± 6.0%, and 41.0 ± 6.2% after non-elective repair. There was no difference in 5 year survival comparing modalities after elective repair for patients younger than 70 years and those with post-dissection aneurysms. CONCLUSION: A multidisciplinary approach offering OSR and cEVAR can deliver comprehensive care for extent I - III TAAA with low early mortality and good midterm survival. Further studies are required to determine the optimal complementary roles of each treatment modality.

Multicenter Study to Evaluate Endovascular Repair of Extent I-III Thoracoabdominal Aneurysms Without Prophylactic Cerebrospinal Fluid Drainage.

OBJECTIVE: To assess outcomes of fenestrated-branched endovascular aortic repair (FB-EVAR) of Extent I-III thoracoabdominal aortic aneurysms (TAAAs) without prophylactic cerebrospinal fluid drainage (CSFD). BACKGROUND: Prophylactic CSFD has been routinely used during endovascular TAAA repair, but concerns about major drain-related complications have led to revising this paradigm. METHODS: We reviewed a multicenter cohort of 541 patients treated for Extent I-III TAAAs by FB-EVAR without prophylactic CSFD. Spinal cord injury (SCI) was graded as ambulatory (paraparesis) or nonambulatory (paraplegia). Endpoints were any SCI, permanent paraplegia, response to rescue treatment, major drain-related complications, mortality, and patient survival. RESULTS: There were 22 Extent I, 240 Extent II and 279 Extent III TAAAs. Thirty-day mortality was 3%. SCI occurred in 45 patients (8%), paraparesis occurring in 23 (4%) and paraplegia in 22 patients (4%). SCI was more common in patients with Extent I-II compared with Extent III TAAAs (12% vs. 5%, P =0.01). Rescue treatment included permissive hypertension in all patients, with CSFD in 22 (4%). Symptom improvement was noted in 73%. Twelve patients (2%) had permanent paraplegia. Two patients (0.4%) had major drain-related complications. Independent predictors for SCI by multivariate logistic regression were sustained perioperative hypotension [odds ratio (OR): 4.4, 95% confidence interval (95% CI): 1.7-11.1], patent collateral network (OR: 0.3, 95% CI: 0.1-0.6), and total length of aortic coverage (OR: 1.05, 95% CI: 1.01-1.10). Patient survival at 3 years was 72%±3%. CONCLUSION: FB-EVAR of Extent I-III TAAAs without CSFD has low mortality and low rates of permanent paraplegia (2%). SCI occurred in 8% of patients, and rescue treatment improved symptoms in 73% of them.

Multicentre International Registry of Open Surgical Versus Percutaneous Upper Extremity Access During Endovascular Aortic Procedures.

OBJECTIVE: To investigate access failure (AF) and stroke rates of aortic procedures performed with upper extremity access (UEA), and compare results of open surgical vs. percutaneous UEA techniques with closure devices. METHODS: A physician initiated, multicentre, ambispective, observational registry (SUPERAXA - NCT04589962) was carried out of patients undergoing aortic procedures requiring UEA, including transcatheter aortic valve replacement, aortic arch, and thoraco-abdominal aortic endovascular repair, pararenal parallel grafts, renovisceral and iliac vessel repair. Only vascular procedures performed with an open surgical or percutaneous (with a suture mediated vessel closure device) UEA were analysed. Risk factors and endpoints were classified according to the Society for Vascular Surgery and VARC-3 (Valve Academic Research Consortium) reporting standards. A logistic regression model was used to identify AF and stroke risk predictors, and propensity matching was employed to compare the UEA closure techniques. RESULTS: Sixteen centres registered 1 098 patients (806 men [73.4%]; median age 74 years, interquartile range 69 - 79 years) undergoing vascular procedures using open surgical (76%) or percutaneous (24%) UEA. Overall AF and stroke rates were 6.8% and 3.0%, respectively. Independent predictors of AF by multivariable analysis included pacemaker ipsilateral to the access (odds ratio [OR] 3.8, 95% confidence interval [CI] 1.2 - 12.1; p = .026), branched and fenestrated procedure (OR 3.4, 95% CI 1.2 - 9.6; p = .019) and introducer internal diameter ≥ 14 F (OR 6.6, 95% CI 2.1 - 20.7; p = .001). Stroke was associated with female sex (OR 3.4, 95% CI 1.3 - 9.0; p = .013), vessel diameter > 7 mm (OR 3.9, 95% CI 1.1 - 13.8; p = .037), and aortic arch procedure (OR 7.3, 95% CI 1.7 - 31.1; p = .007). After 1:1 propensity matching, there was no difference between open surgical and percutaneous cohorts. However, a statistically significantly higher number of adjunctive endovascular procedures was recorded in the percutaneous cohort (p < .001). CONCLUSION: AF and stroke rates during complex aortic procedures employing UEA are non-negligible. Therefore, selective use of UEA is warranted. Percutaneous access with vessel closure devices is associated with similar complication rates, but more adjunctive endovascular procedures are required to avoid surgical exposure.

Fenestrated-branched endovascular repair for distal thoracoabdominal aortic pathology after total aortic arch replacement with frozen elephant trunk.

OBJECTIVE: To report the outcomes of fenestrated-branched endovascular repair (FBEVAR) for thoracoabdominal aortic pathology after total aortic arch replacement with frozen elephant trunk (TAR+FET). METHODS: Interrogation of prospectively maintained databases from four high-volume aortic centers identified consecutive patients treated with distal FBEVAR after prior TAR+FET between August 2013 and September 2020. The primary end point was 30-day/in-hospital mortality. Secondary end points were technical success, early clinical success, midterm survival, and freedom from reintervention. Data are presented as median (interquartile range). RESULTS: A total of 39 patients (21 men; median age, 73 years [67-75 years]) with degenerative (n = 22) and postdissection thoracoabdominal aortic aneurysms (n = 17) (median diameter, 71 mm [61-78 mm]) were identified. Distal FBEVAR was intended in 27 patients (median interval, 9.8 months [6.2-16.6 months]), anticipated in 7, and unexpected in 5. A total of 31 patients had a two- (n = 24) or three-stage (n = 7) distal FBEVAR. Renovisceral target vessel preservation was 99.3% (145 of 146). Early primary and secondary technical success was 92% and 97%, respectively. Thirty-day mortality was 2.6% (n = 1; respiratory failure and spinal cord ischemia [SCI]). Six survivors also developed SCI, which was associated with complete (n = 4) or partial recovery (n = 2) at hospital discharge. No patients required renal replacement therapy or suffered a stroke. Early clinical success was 95%. Median follow-up was 30.5 months (23.7-49.7 months). Eleven patients required 16 late reinterventions. Estimated 3-year survival and freedom from reintervention were 84% ± 6% and 63% ± 10%, respectively. CONCLUSIONS: Distal FBEVAR after prior TAR+FET is associated with high technical success and low early mortality. The risk of SCI is significant although the majority of patients demonstrate full or partial recovery before hospital discharge. Midterm patient survival is favorable, but there remains a high requirement for late reintervention. FBEVAR represents an acceptable alternative to distal open thoracoabdominal aortic aneurysm repair.

Complex Endovascular Repair of Paravisceral Infective Native Aortic Aneurysms.

OBJECTIVE: To report the early and mid-term outcome of complex endovascular repair (EVAR) for paravisceral infective native aortic aneurysms (INAA). METHODS: Interrogation of a prospectively maintained database identified consecutive patients who underwent non-elective complex EVAR for paravisceral INAAs in a single institution between December 2013 and June 2020. All patients were considered to have definite INAAs based on diagnostic criteria. Patients who had prior aortic repair were excluded. RESULTS: A total of 26 patients (19 men; mean age 67 years [SD = 11.4]; median diameter 60 mm [IQR: 55-73]) with acute symptomatic (n = 24) or contained ruptured (n = 2) aneurysms underwent surgeon-modified fenestrated EVAR (SM-FEVAR; n = 24) or chimney-periscope EVAR (CHIMPS; n = 2). Median observed follow-up was 36.2 months (18.3-53.5). Nine patients had positive venous blood cultures and a further seven had recent or concomitant infection. All patients received pre- and post-operative antibiotic therapy and rifampicin-soaked endografts. A total of 95 vessels were targeted for preservation and 86 were stent-grafted. One vessel occluded intra-operatively and a further 3 occluded within 30 days. The 30-day/in-hospital mortality was 11.5% (n = 3), and the estimated 1- and 3-year survival (±SD) was 85% ± 7%. Infection-related complications (IRCs) occurred in two patients: both developed new INAA within 30 days of index repair and were treated by EVAR with no mortality. Estimated 3-year freedom from late re-intervention was 100%. One patient required infrarenal EVAR for a non-infective aneurysm at 43 months. CONCLUSION: Complex EVAR for paravisceral INAAs is associated with acceptable early and mid-term outcomes and is an acceptable alternative to open surgery. We propose that these patients are managed with long-term antimicrobials, impregnation of graft material with rifampicin, and rigorous post-operative surveillance. CLINICAL IMPACT: A multi-disciplinary approach is required to deliver the best possible outcome for patients with this challenging aortic pathology.

Fenestrated-Branch Endovascular Repair After Prior Abdominal Aortic Aneurysm Repair.

OBJECTIVE: To report the outcome of fenestrated and branch endovascular aortic repair (FEVAR-BEVAR) for asymptomatic and acute symptomatic proximal aortic pathology in patients with prior open (OSR) or endovascular (EVAR) abdominal aortic aneurysm (AAA) repair. METHODS: This was a single centre retrospective study of consecutive patients with non-ruptured (asymptomatic and acute symptomatic) proximal aortic pathology after prior OSR or EVAR treated between December 2007 and February 2020. The primary endpoint was 30 day/in hospital mortality. Secondary endpoints were technical success, primary clinical success, and Kaplan-Meier estimates of medium term survival and freedom from re-intervention. Data are presented as median (interquartile range [IQR]). The effect of covariates on medium term survival was estimated using multivariable (Cox proportional hazards model) analysis. A p value < .05 was considered to be statistically significant. RESULTS: Ninety-two patients (83 men; median age 75 years [IQR 71 - 80 years]; median diameter 73 mm [IQR 64 - 89 mm]; 82 elective, 10 acute) underwent FEVAR-BEVAR after prior OSR (n = 47) or EVAR (n = 45). Indications for intervention were aneurysmal degeneration with or without type 1a endoleak (n = 57; four juxtarenal [JR] AAA, 21 extent II/III, 32 extent IV thoraco-abdominal aortic aneurysms); type 1a endoleak alone (n = 27) and to create a more durable repair after acute infrarenal EVAR (n = 8; JRAAA). In total, 348 renovisceral vessels were targeted for preservation and 324 were stent grafted. Twenty-four unstented vessels comprised one bypass, 11 scallops and six fenestrations intentionally not stent grafted, two vessels occluded before graft implantation, and four vessels occluded intra-operatively. Primary technical success was 95.6%. The thirty day mortality rate was 1.1% and one patient each (1.1%) required permanent dialysis or developed temporary spinal cord ischaemia. Early primary clinical success was 94.6%. Median follow up was 36 months (IQR 23 - 64 months). Estimated overall survival (± standard error) at one, two, and three years was 86% ± 4%, 85% ± 4%, and 70% ± 5%, respectively. Multivariable analysis did not demonstrate any independent predictors of survival. Four target vessels occluded during follow up. Nineteen patients underwent 28 late re-interventions, with almost half performed for issues arising distal to the FEVAR-BEVAR. Patients treated with a cuff were statistically significantly more likely to require distal re-intervention compared with those treated by relining (9/49 vs. 1/43, p = .018 [odds ratio 9.3, 95% confidence interval 1.2 - 423]). In patients with prior EVAR alone, this did not reach statistical significance (cuff 7/25 vs. relining 1/20, p = .059 [odds ratio 7.1, 95% confidence interval 0.8 - 350]). Estimated freedom from re-intervention at one, two, and three years was 88% ± 3%, 81% ± 4%, and 81% ± 4%, respectively. CONCLUSION: FEVAR-BEVAR after prior OSR or EVAR is associated with low peri-operative morbidity and mortality, and acceptable medium term survival and freedom from re-intervention. Treatment with a FEVAR-BEVAR cuff is associated with a higher requirement for distal re-intervention than relining of the original repair.

Elective Fenestrated and Branched Endovascular Thoraco-abdominal Aortic Repair with Supracoeliac Sealing Zones and without Prophylactic Cerebrospinal Fluid Drainage: Early and Medium-term Outcomes.

OBJECTIVE: To report the outcome of elective fenestrated and branch (FEVAR-BEVAR) endovascular aortic repair with supracoeliac (SC) sealing zones and the impact of staged repair without prophylactic cerebrospinal fluid (CSF) drainage on the incidence of spinal cord ischaemia (SCI). METHODS: Two hundred and seventy consecutive patients (217 men; mean [SD] age, 72.8 ± 6.3 years; median (IQR) diameter 65 mm [62-75 mm]) with juxtarenal (JRAAA) (n = 69) or thoraco-abdominal aortic aneurysms (TAAAs) (n = 201) underwent elective FEVAR (n = 192) or BEVAR (n = 78) with renovisceral stent grafting, proximal SC (Zones 1-5; <40 mm [n = 83]; ≥40 mm [n = 187]) and distal infrarenal aorto-iliac sealing zone (Zones 9-11) between December 2008 and September 2017. A spinal cord protection protocol (SCPP) including staging without prophylactic CSF drainage was introduced in September 2012. RESULTS: A total of 1026 renovisceral vessels (mean 3.8 ± 0.5 per patient) were targeted for preservation. One patient (0.4%) died in the institution within 30 days and 31 (11.4%) developed 36 major non-fatal complications including unplanned permanent dialysis (n = 1, 0.4%) and non-ambulatory SCI (n = 6, 2.2%). In patients with <40 mm SC coverage, none were staged or had prophylactic CSF drains and none developed SCI. In patients with ≥40 mm SC coverage, SCI occurred in 3.3% (pre-SCPP: 4/20 [20%; none staged, 13 prophylactic CSF drains] vs. post-SCPP: 2/167 [1.2%; 89 staged, no prophylactic CSF drains]; p = .001 [OR = 19.9]). Estimated survival (±SE) at one, two and three years was 92.6% ± 1.6%, 86.5% ± 2.4%, and 73.8% ± 3.5%, respectively, with no significant difference comparing extent of aneurysm or SC coverage. Forty-three (15.9%) patients required late re-intervention. Estimated freedom from re-intervention at one, two and three years was 91.9% ± 1.8%, 85.1% ± 2.5%, and 79.5% ± 3.2%, respectively. CONCLUSION: Elective endovascular thoraco-abdominal aortic repair with SC sealing zones can be performed with low peri-operative risk and good medium-term outcomes. Selective staging without prophylactic CSF drainage contributed to a significant reduction in the incidence of SCI.

Endovascular Repair of Acute Thoraco-abdominal Aortic Aneurysms.

OBJECTIVES: The outcome of endovascular repair (EVAR) for acute thoraco-abdominal aortic aneurysm (TAAA) is reported and the applicability of the t-Branch off the shelf (OTS) device is determined. METHODS: Interrogation of a prospectively maintained database identified all patients who underwent EVAR for acute TAAA between September 2012 (when the first non-elective t-Branch case was performed) and November 2015. Early and medium-term outcomes were analysed. Survival and re-intervention-free survival were calculated by Kaplan-Meier analysis. RESULTS: A total of 39 patients (27 men; mean ± SD age, 72 ± 8 years) were treated for acute symptomatic (n = 29) or ruptured (n = 10) TAAA (20 anatomical extent I-III, 19 extent IV). Fourteen patients had mycotic aneurysms. The mean aneurysm diameter was 80 ± 20 mm. The mean ± SD follow-up was 21.4 ± 15.4 months. Surgeon modified fenestrated EVAR was used in 24 patients, chimney/periscope EVAR in two, and t-Branch in 13 (33%) patients. Aortic coverage was greater than 40 mm above the coeliac axis in all patients. A total of 127 target vessels (TVs) were preserved (mean 3.3 per patient) and two occluded within 30 days. The 30 day mortality was 26%. Four (10%) patients developed spinal cord ischaemia (SCI): two with paraplegia died within 30 days, and two with paraparesis recovered completely with blood pressure manipulation and cerebrospinal fluid drainage. Estimated overall survival (±SD) at 12 and 24 months was 71.8 ± 7.2% and 63.2 ± 7.9%, respectively. Estimated freedom from re-intervention at 12 and 24 months was 93 ± 4.8% and 85.3 ± 6.8%, respectively. CONCLUSIONS: EVAR for acute TAAA is associated with acceptable early and mid-term results in patients who have no other treatment options. Only one third of these patients were suitable for the t-Branch device, indicating that further advances in device design are required to treat the majority of acute TAAA patients with commercially available OTS technology.

Effect of endovascular and open abdominal aortic aneurysm repair on thrombin generation and fibrinolysis.

BACKGROUND: Abdominal aortic aneurysm (AAA) is associated with a prothrombotic diathesis that may increase the risk of cardiovascular events. This diathesis is exacerbated in the short term by open aneurysm repair (OAR) and endovascular aneurysm repair (EVAR). However, the effect of EVAR and OAR on coagulation and fibrinolysis in the medium and long term is poorly understood. The purpose of this study was to investigate the medium-term effects of EVAR and OAR on thrombin generation, neutralization, and fibrinolysis. METHODS: Prothrombin fragment (PF)1+2, thrombin antithrombin (TAT) complex, plasminogen activator inhibitor (PAI) activity, and tissue-plasminogen activator (t-PA) antigen were measured in eight age-matched controls (AMCs), 29 patients with AAA immediately before (preoperatively) and 12 months after EVAR (post-EVAR), and in 11 patients at a mean of 16 months after OAR (post-OAR). RESULTS: Preoperatively, PF1+2 levels were significantly higher in patients with AAAs than in AMC. PF1+2 levels post-EVAR and post-OAR were significantly lower than preoperative values and similar to AMC. There was no significant difference in TAT, PAI, or t-PA between AMC, AAA preoperatively, and post-EVAR. Post-OAR, PAI activity was significantly higher than in preoperative patients. CONCLUSIONS: AAA is associated with increased thrombin generation without upregulation of fibrinolysis. The prothrombotic, hypofibrinolytic diathesis observed in patients with AAA returns toward normal in the medium term after EVAR and OAR, although there is a trend toward decreased fibrinolysis post-OAR.

Assessment of renal function by means of cystatin C following standard and fenestrated endovascular aneurysm repair.

BACKGROUND: Cystatin C (Cyst C) is more sensitive marker for early renal injury. However, serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) are still used as the standard renal markers after endovascular aortic aneurysm repair (EVAR). The goal of this study was to compare the efficacy of Cyst C, sCr, and eGFR as markers of renal function after EVAR. PATIENTS AND METHODS: This study examined 29 patients (27 men) with a mean age of 76.9 years (range, 55-89 years) undergoing standard (n = 19) and fenestrated (n = 10) EVAR for abdominal aortic aneurysm (AAA) of mean diameter 6.9 cm (range, 5.5-10 cm). Cyst C and sCr were measured and eGFR calculated before and 1 day and 1, 6, and 12 months after EVAR. RESULTS: At 24 hours after procedure, a significant increase in Cyst C (P < 0.005) and sCr (P = 0.028) and significant decrease in eGFR (P = 0.04) were seen. Cyst C continued to increase and was significantly higher at 1 (P < 0.002), 6 (P < 0.005), and 12 (P < 0.005) months compared with baseline. By contrast, sCr and eGFR did not show any significant change at 1, 6, and 12 months from the baseline level. Cyst C increased significantly postoperatively regardless of the baseline renal function. None of the patients required renal replacement therapy. CONCLUSIONS: EVAR is associated with a significant increase in Cyst C starting 24 hours after the procedure and is maintained for 12 months. sCr and eGFR only show significant change at 24 hours and therefore may underestimate long-term renal damage after EVAR.

Changes in thrombin generation, fibrinolysis, platelet and endothelial cell activity, and inflammation following endovascular abdominal aortic aneurysm repair.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a chronic inflammatory condition associated with a prothrombotic, hypofibrinolytic diathesis that may increase the risk of cardiovascular events. The effect of endovascular aneurysm repair (EVAR) on this prothrombotic diathesis is not fully understood, especially over the medium and long term. A better understanding of these postintervention changes may improve the risk of cardiovascular complications in the long term. The purpose of this study was to examine thrombin generation, fibrinolysis, platelet and endothelial activation, and the inflammatory response during the 12 months following EVAR. METHODS: Twenty-nine patients (mean age, 76.9 years) undergoing EVAR for AAA (mean diameter 6.9 cm) had prothrombin fragment (PF) 1 + 2, thrombin-antithrombin complex (TAT), plasminogen activator inhibitor (PAI) activity, tissue plasminogen activator (t-PA) activity and antigen, soluble P- and E-selectin, and highly sensitive C-reactive protein (hsCRP) measured before and at 24 hours, and 1, 6, and 12 months after surgery. RESULTS: PF1 + 2 were markedly elevated prior to EVAR and remained so at 24 hours and 1 month, but had decreased significantly at 6 and 12 months. TAT was also elevated prior to EVAR and increased still further by 24 hours, but fell to below baseline levels thereafter. PAI activity and t-PA antigen were normal prior to EVAR, increased significantly at 24 hours, and then fell to baseline levels. t-PA activity was only detectable at 1 and 6 months; there was a significant rise in soluble P- and E-selectin after EVAR, which was sustained for 12 months. hsCRP increased transiently in response to EVAR but returned to preoperative levels by 1 month. CONCLUSIONS: The prothrombotic, hypofibrinolytic diathesis associated with AAA is normalized 12 months after EVAR. This beneficial systemic effect of EVAR for AAA disease may help protect patients against future thromboembolic cardiovascular events.

Endovascular aneurysm repair reverses the increased titer and the inflammatory activity of interleukin-1α in the serum of patients with abdominal aortic aneurysm.

OBJECTIVE: To examine serum cytokine/chemokine profiles before and 6 months after endovascular repair (EVAR) of abdominal aortic aneurysm (AAA) and to determine whether they correlate with serum inflammatory activity using an in vitro model of leukocyte recruitment. METHODS: Serum IL-1-α, IL-1ß, IL-4, IL-6, IL-8, IL-10, IFN-γ, IP-10, MCP-1, TNF-α, and TNF-ß were measured using a cytometry-based immunoassay. To test patient serum for direct inflammatory activity, human endothelial cells (EC) were stimulated with 30% patient serum for 24 hours. To test patient serum for the ability to prime EC for inflammatory responses, EC were incubated with 30% patient serum for 24 hours, followed by stimulation with low-dose (5 U/mL) TNF for 4 hours. Under both regimens of stimulation, the degree of EC activation was assessed by assaying neutrophil recruitment in a flow-based model. RESULTS: Only IL-1α (67.9 ± 10.4 pg/mL vs 41.9 ± 7.4 pg/mL) and IL-8 (51.5 ± 5.1 vs 32.6 ± 4.7 pg/mL) changed significantly after surgery. Patient serum alone was unable to activate EC. However, serum from both time points could prime EC responses to low-dose TNF. Thus, after priming with preoperative serum, EC stimulated with TNF could recruit 76.7 ± 12.0 neutrophils/mm(2) into the subendothelial cell space. Post-EVAR serum was significantly less effective (44.4 ± 10.2 neutrophils/mm(2)). This reduction in neutrophil recruitment correlated with reduced IL-1α in post-EVAR serum. The addition of a neutralizing antibody against IL-1α to pre-EVAR serum inhibited EC priming and neutrophil recruitment, strongly implying that this cytokine was the priming agent. CONCLUSION: EVAR reduces serum IL-1α and its inflammatory activity in patient serum. IL-1α is, therefore, implicated in the molecular pathology of AAAs and may have potential as a clinically useful biomarker.

Coagulation, fibrinolysis, and platelet activation in patients undergoing open and endovascular repair of abdominal aortic aneurysm.

BACKGROUND: Endovascular aneurysm repair (EVAR) is associated with an improved perioperative mortality compared to open surgical repair. This benefit may reflect reduced incidence of microvascular and macrovascular thrombotic complications after EVAR. PURPOSE: The purpose of this study was to review and compare the effects of abdominal aortic aneurysm (AAA), open surgical repair, and EVAR on coagulation, fibrinolysis, and platelet activation. METHODS: A MEDLINE (1966-2010) and Cochrane library search for articles relating to the effects of AAA, open surgical repair, and EVAR on hemostasis was performed utilizing and cross-linking terms such as clotting, fibrinolysis, AAA, EVAR, and open surgical repair. Studies with a small cohort of patients (less than 7) or in which values of assessed biomarkers were not included were rejected. RESULTS: AAA is associated with increased thrombin generation, activity, and fibrin turnover as evidenced by increased plasma levels of thrombin-antithrombin III-complex (TAT), activated protein C-protein C inhibitor (APC-PCI), fibrin-monomer-fibrinogen (FM-F), F1+2, fibrinogen, and D-dimer. The extent of hemostatic derangement correlates with the volume of intraluminal thrombus. This procoagulant state is exaggerated in the immediate perioperative period after both open surgical repair and EVAR, but is attenuated at medium-term follow-up although not normalized. CONCLUSION: The resultant prothrombotic diathesis after open surgical repair and EVAR may account for the high level of perioperative thrombotic complications.

Ultrasound-guided foam sclerotherapy is a safe and clinically effective treatment for superficial venous reflux.

OBJECTIVE: To test the hypothesis that ultrasound-guided foam sclerotherapy (UGFS) is a safe and durable treatment for superficial venous reflux (SVR) associated with CEAP clinical grade 2-6 disease. METHODS: This was an interrogation of a prospectively gathered computerized database. RESULTS: Between March 23, 2004 and December 31, 2009, 977 patients (1252 legs) underwent UGFS for unilateral (702 legs) or bilateral (550 legs) SVR in association with CEAP clinical grade 2-3 (n = 868), 4 (n = 232), or 5/6 (n = 152) disease. The following reflux in 1417 venous segments was treated: primary great saphenous vein (GSV) (n = 745); recurrent GSV (n = 286), primary small saphenous vein (SSV) (n = 189), recurrent SSV (n = 50); primary anterior accessory saphenous vein (AASV) (n = 93); recurrent AASV (n = 46); vein of the popliteal fossa (VOPF) (n = 5), and Giacomini vein (GV) (n = 3). Three hundred forty-eight legs (27.8%) had undergone previous surgery. Three patients suffered post-UGFS deep vein thrombosis (DVT) and one a pulmonary embolus (PE), all within the first month (0.4% venous thrombo-embolic complication rate). Five patients (0.5%) had transient visual disturbance at the time of, or shortly after, treatment. No other neurologic or serious complications were reported. During a mean (range) follow-up of 28 (<1 to 68) months, 161 (12.9%) legs underwent a further session of UGFS for truncal VV at a mean (range) of 17 (<1 to 63) months following the first treatment. In 52 legs, retreatment was due to the development of new SVR and in 109 legs was for true recurrence (8.7% complete or partial recanalization rate leading to treatment). There was no significant difference in retreatment rates between UGFS for GSV and SSV reflux or between UGFS for primary or recurrent disease. CONCLUSION: UGFS for CEAP 2-6 SVR is associated with a low complication and retreatment rate. However, as patients are at risk of developing recurrent and new SVR they should be kept under review. Further UGFS for new or recurrent disease is simple, safe, and effective.

Changes in health-related quality of life after ultrasound-guided foam sclerotherapy for great and small saphenous varicose veins.

BACKGROUND: Health-related quality of life (HRQOL) improves after superficial venous surgery for varicose veins, but the effect of ultrasound-guided foam sclerotherapy on HRQOL is unknown. The aim of this study was to determine changes in HRQOL after ultrasound-guided foam sclerotherapy for varicose veins. METHODS: Consecutive patients undergoing ultrasound-guided foam sclerotherapy for varicose veins were sent the Short Form 12 (SF-12) questionnaire, a generic measure of HRQOL, and the Aberdeen Varicose Vein Symptom Score (AVSS) questionnaire, a disease-specific measure of HRQOL, 1 week before treatment and 1, 6, and 12 months after treatment. RESULTS: The study enrolled 296 patients (34% male; 395 treated legs) with a median age of 57 years (range, 22-89 years). Of these, 24% had had previous superficial venous surgery, and 66% were CEAP C(2-3) (uncomplicated varicose veins). Questionnaire completion rates were 82%, 73%, and 69% at 1, 6, and 12 months after treatment. The median Physical Component Summary score of the SF-12 (higher score indicates better HRQOL) improved from 47.6 pretreatment to 49.4 at 1 month (P < .008, Wilcoxon signed rank test), to 51.9 at 6 months (P < .0005), and to 52.9 at 12 months (P < .0005). The median AVSS (lower score indicates better HRQOL) improved from 19.0 pretreatment to 16.5 at 1 month (P < .0005), to 8.7 at 6 months (P < .0005), and to 8.6 at 12 months (P < .0005). CONCLUSIONS: Ultrasound-guided foam sclerotherapy for great and small saphenous varicose veins leads to significant improvements in generic and disease-specific HRQOL for at least 12 months after treatment.

Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial: An intention-to-treat analysis of amputation-free and overall survival in patients randomized to a bypass surgery-first or a balloon angioplasty-first revascularization strategy.

BACKGROUND: A 2005 interim analysis of the Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial showed that in patients with severe lower limb ischemia (SLI; rest pain, ulceration, gangrene) due to infrainguinal disease, bypass surgery (BSX)-first and balloon angioplasty (BAP)-first revascularization strategies led to similar short-term clinical outcomes, although BSX was about one-third more expensive and morbidity was higher. We have monitored patients for a further 2.5 years and now report a final intention-to-treat (ITT) analysis of amputation-free survival (AFS) and overall survival (OS). METHODS: Of 452 enrolled patients in 27 United Kingdom hospitals, 228 were randomized to a BSX-first and 224 to a BAP-first revascularization strategy. All patients were monitored for 3 years and more than half for >5 years. RESULTS: At the end of follow-up, 250 patients were dead (56%), 168 (38%) were alive without amputation, and 30 (7%) were alive with amputation. Four were lost to follow-up. AFS and OS did not differ between randomized treatments during the follow-up. For those patients surviving 2 years from randomization, however, BSX-first revascularization was associated with a reduced hazard ratio (HR) for subsequent AFS of 0.85 (95% confidence interval [CI], 0.5-1.07; P = .108) and for subsequent OS of 0.61 (95% CI, 0.50-0.75; P = .009) in an adjusted, time-dependent Cox proportional hazards model. For those patients who survived for 2 years after randomization, initial randomization to a BSX-first revascularization strategy was associated with an increase in subsequent restricted mean overall survival of 7.3 months (95% CI, 1.2-13.4 months, P = .02) and an increase in restricted mean AFS of 5.9 months (95% CI, 0.2-12.0 months, P = .06) during the subsequent mean follow-up of 3.1 years (range, 1-5.7 years). CONCLUSIONS: Overall, there was no significant difference in AFS or OS between the two strategies. However, for those patients who survived for at least 2 years after randomization, a BSX-first revascularization strategy was associated with a significant increase in subsequent OS and a trend towards improved AFS.