Faculty Bibliography

In atherosclerosis, resident vascular smooth muscle cells (VSMCs) in the blood vessels become highly plastic and undergo phenotypic switching from the quiescent, contractile phenotype to the migratory and proliferative, synthetic phenotype. Additionally, recent VSMC lineage-tracing mouse models of atherosclerosis have found that VSMCs transdifferentiate into macrophage-like and osteochondrogenic cells and make up to 70% of cells found in atherosclerotic plaques. Given VSMC phenotypic switching is regulated by microRNA-145 (miR-145), we hypothesized that nanoparticle-mediated delivery of miR-145 to VSMCs has the potential to mitigate atherosclerosis development by inhibiting plaque-propagating cell types derived from VSMCs. To test our hypothesis, we synthesized miR-145 micelles targeting the C-C chemokine receptor-2 (CCR2), which is highly expressed on synthetic VSMCs. When miR-145 micelles were incubated with human aortic VSMCs in vitro, >90% miR-145 micelles escaped the lysosomal pathway in 4 hours and released the miR cargo under cytosolic levels of glutathione, an endogenous reducing agent. As such, miR-145 micelles rescued atheroprotective contractile markers, myocardin, α-SMA, and calponin, in synthetic VSMCs in vitro. In early-stage atherosclerotic ApoE^-/- mice, one dose of miR-145 micelles prevented lesion growth by 49% and sustained an increased level of miR-145 expression after 2 weeks post-treatment. Additionally, miR-145 micelles inhibited 35% and 43% plaque growth compared to free miR-145 and PBS, respectively, in mid-stage atherosclerotic ApoE^-/- mice. Collectively, we present a novel therapeutic strategy and cell target for atherosclerosis, and present miR-145 micelles as a viable nanotherapeutic that can intervene atherosclerosis progression at both early and later stages of disease.

OBJECTIVE:We reviewed the complications associated with perioperative lumbar drain (LD) placement for endovascular aortic repair. METHODS:Patients who had undergone perioperative LD placement for endovascular repair of thoracic and thoracoabdominal aortic pathologies from 2010 to 2019 were reviewed. The primary endpoints were major and minor LD-associated complications. Complications that had resulted in neurological sequelae or had required an intervention or a delay in operation were defined as major. These included intracranial hemorrhage, symptomatic spinal hematoma, cerebrospinal fluid (CSF) leak requiring intervention, meningitis, retained catheter tip, arachnoiditis, and traumatic (or bloody) tap resulting in delayed operation. Minor complications were defined as a bloody tap without a delay in surgery, asymptomatic epidural hematoma, and CSF leak with no intervention required. Isolated headaches were recorded separately owing to the minimal clinical impact. RESULTS:A total of 309 LDs had been placed in 268 consecutive patients for 222 thoracic endovascular aortic repairs, 85 complex endovascular aortic repairs (EVARs; fenestrated branched EVAR/parallel grafting), and 2 EVARs (age, 65 ± 13 years; 71% male) for aortic pathology, including aneurysm (47%), dissection (49%), penetrating aortic ulcer (3%), and traumatic injury (0.6%). A dedicated neurosurgical team performed all LD procedures; most were performed by the same individual, with a technical success rate of 98%. Radiologic guidance was required in 3%. The reasons for unsuccessful placement were body habitus (n = 2) and severe spinal disease (n = 3). Most were placed prophylactically (96%). The overall complication rate was 8.1% (4.2% major and 3.9% minor). Major complications included spinal hematoma with paraplegia in 1 patient, intracranial hemorrhage in 2, meningitis in 2, arachnoiditis in 3, CSF leak requiring a blood patch in 3, bloody tap delaying the operation in 1, and a retained catheter tip in 1 patient. Patients who had undergone previous LD placement had experienced significantly more major LD-related complications (12.2% vs 3%; P = .019). The rate of total LD-associated complications did not differ between prophylactic and emergent therapeutic placements (8.1% vs 7.7%; P = 1.00) nor between major or minor complications. On multivariate analysis, previous LD placement and an overweight body mass index were the only independent predictors of major LD-related complications. CONCLUSIONS:The complications associated with LD placement can be severe even when performed by a dedicated team. Previous LD placement and overweight body mass index were associated with a significantly greater risk of complications; however, emergent therapeutic placement was not. Although these risks are justified for therapeutic LD placement, the benefit of prophylactic LD placement to prevent paraplegia should be weighed against these serious complications.

The repair of tandem carotid lesions has been described using myriad methods, often involving a hybrid approach of stenting with carotid endarterectomy. Because of the worrisome stroke rates associated with this method, we have reported an innovative technique of transcarotid artery revascularization (TCAR) for tandem lesions in a patient with high-grade stenosis of the right common and internal carotid arteries. Technical success was achieved with TCAR via retrograde and antegrade access using dynamic flow reversal for the treatment of both lesions. The patient experienced no postoperative complications, highlighting the successful repair of tandem carotid lesions using TCAR in a patient who is too high risk for carotid endarterectomy.

OBJECTIVE:Revascularization of the left subclavian artery (LSA) during zone 2 thoracic endovascular aortic repair (TEVAR) maintains collateral circulation to decrease ischemic complications, including stroke, spinal cord ischemia, and upper extremity ischemia. Both open surgical and endovascular LSA revascularization techniques have been described, each with unique risks and benefits. We describe our "periscope sandwich" technique for the LSA during zone 2 TEVAR, which maintains antegrade access to the distal abdominal aorta if subsequent interventions are necessary. Technical results and short-term outcomes are compared with LSA open surgical debranching. METHODS:A single-institution retrospective review was performed for patients requiring zone 2 TEVAR with LSA revascularization by periscope sandwich technique or open surgical debranching with subclavian to carotid transposition (SCT) or carotid-subclavian bypass (CSB). The presenting aortic disease and perioperative details were recorded. Intraoperative angiography and postoperative computed tomography images were reviewed for occurrence of endoleak and branch patency. RESULTS:Between January 2013 and December 2018, the LSA was revascularized by periscope sandwich in 18 patients, SCT in 22 patients, and CSB in 13 patients. Compared with open surgical debranching, periscope sandwich had a lower median estimated blood loss (100 mL vs 200 mL for pooled SCT and CSB; P = .03) and lower median case duration (133.5 minutes vs 226 minutes; P < .001). Contrast material volume (120 mL vs 120 mL; P = .98) and fluoroscopy time (13.1 minutes vs 13.3 minutes; P = .92) did not differ significantly between the groups. There was no difference in aorta-related mortality (P = .14), and LSA patency was 100%. Median follow-up for the periscope sandwich group was 11 months, with an overall estimated 91% freedom from gutter leak at 6 months. CONCLUSIONS:LSA periscope sandwich technique provides safe and effective LSA revascularization during zone 2 TEVAR. LSA periscope sandwich can be used emergently with off-the-shelf endovascular components and facilitates future branched-fenestrated endovascular repair of thoracoabdominal aortic diseases.

BACKGROUND:Thoracic endovascular aortic repair (TEVAR) for type B aortic dissections is used to promote false lumen (FL) thrombosis and favorable aortic remodeling, but its impact on occlusion of FL origin branch vessels has not been widely described. We compare FL versus true lumen (TL) branch vessel patency after TEVAR. METHODS:Patients treated by TEVAR for type B aortic dissection in zones 2-5 in the Vascular Quality Initiative from 2009 to 2018 were evaluated. The primary outcome was postoperative branch patency. Secondary outcomes were need for branch vessel intervention, preoperative origin, and postoperative patency of individual branch vessels (celiac, superior mesenteric artery, renal arteries, and iliac arteries). A subset analysis was performed comparing acute and chronic dissections. RESULTS:Of 11,774 patients, 1,484 met criteria for analysis. The left renal was the most common to have FL origin (21.6%), whereas right and left common iliac arteries were the most likely to originate off both lumens (BLs; 22% and 24%). Branch vessels that originated from the TL, FL, BLs, or were obstructed had postoperative patency rates of 99%, 99%, 99%, and 87% (P < 0.0001). Branch vessel treatment was performed in 5% of patients. The right (2.5%) and left (2.8%) renal arteries were the most frequently obstructed branches postoperatively. On multivariate analysis, preoperatively obstructed branches (odds ratio 0.03, P < 0.0001) were negatively associated with postoperative branch patency and branch vessel treatment (odds ratio 3.8, P = 0.004) was positively associated with postoperative patency. FL or BL origin, number of zones covered by TEVAR, urgency, dissection chronicity (acute versus chronic), and demographics were not independently associated with patency. These findings remained unchanged in the subset analysis of only acute dissections. CONCLUSIONS:Branch vessel patency rates after TEVAR for a type B aortic dissection are high and are not significantly different for FL or BL origin vessels compared with TL vessels. Branches that are patent before TEVAR almost always remain patent after TEVAR, but branch vessel stenting may be required in less than 5%.

OBJECTIVE:The optimal revascularization modality in secondary aortoenteric fistula (SAEF) remains unclear in the literature. The purpose of this investigation was to determine the revascularization approach associated with the lowest morbidity and mortality using real-world data in patients with SAEF. METHODS:A retrospective, multi-institutional study of SAEF from 2002 to 2014 was performed using a standardized database. Baseline demographics, comorbidities, and operative and postoperative variables were recorded. The primary outcome was long-term mortality. Descriptive statistics, Kaplan-Meier survival analysis, and univariate and multivariate analyses were performed. RESULTS:During the study period, 182 patients at 34 institutions from 11 countries presented with SAEF (median age, 72 years; 79% male). The initial aortic procedures that resulted in SAEF were 138 surgical grafts (76%) and 42 endografts (23%), with 2 unknown; 102 of the SAEFs (56%) underwent complete excision of infected aortic graft material, followed by in situ (in-line) bypass (ISB), including antibiotic-soaked prosthetic graft (53), autogenous femoral vein (neoaortoiliac surgery; 17), cryopreserved allograft (28), and untreated prosthetic grafts (4). There were 80 patients (44%) who underwent extra-anatomic bypass (EAB) with infected graft excision. Overall median Kaplan-Meier estimated survival was 319 days (interquartile range, 20-2410 days). Stratified by EAB vs ISB, there was no significant difference in Kaplan-Meier estimated survival (P = .82). In comparing EAB vs ISB, EAB patients were older (74 vs 70 years; P = .01), had less operative hemorrhage (1200 mL vs 2000 mL; P = .04), were more likely to initiate dialysis within 30 days postoperatively (15% vs 5%; P = .02), and were less likely to experience aorta-related hemorrhage within 30 days postoperatively (3% aortic stump dehiscence vs 11% anastomotic rupture; P = .03). There were otherwise no significant differences in presentation, comorbidities, and intraoperative or postoperative variables. Multivariable Cox regression showed that the duration of antibiotic use (hazard ratio, 0.92; 95% confidence interval, 0.86-0.98; P = .01) and rifampin use at time of discharge (hazard ratio, 0.20; 95% confidence interval, 0.05-0.86; P = .03) independently decreased mortality. CONCLUSIONS:These data suggest that ISB does not offer a survival advantage compared with EAB and does not decrease the risk of postoperative aorta-related hemorrhage. After repair, <50% of SAEF patients survive 10 months. Each week of antibiotic use decreases mortality by 8%. Further study with risk modeling is imperative for this population.