Faculty Bibliography

During atherosclerosis, vascular smooth muscle cells (VSMCs) undergo a phenotypic transition from a healthy contractile state into pathological phenotypes including a proliferative and migratory, synthetic phenotype and osteochondrogenic-like phenotype that exacerbate plaques. Thus, inhibiting the transition of healthy, quiescent VSMCs to atherogenic cell types has the potential to mitigate atherosclerosis. To that end, previously, we reported that delivery of microRNA-145 (miR-145, a potent gatekeeper of the contractile VSMC phenotype) using nanoparticle micelles limited atherosclerotic plaque growth in murine models of atherosclerosis. Building on this preclinical data and toward clinical application, in this study, we tested the therapeutic viability of miR-145 micelles on patient-derived VSMCs and evaluated their effects based on disease severity. We collected vascular tissues from 11 patients with healthy, moderate, or severe stages of atherosclerosis that were discarded following vascular surgery or organ transplant, and isolated VSMCs from these tissues. We found that with increasing disease severity, patient-derived VSMCs had decreasing levels of contractile markers (miR-145, ACTA2, MYH11) and increasing levels of synthetic markers (KLF4, KLF5, and ELK1). Treatment with miR-145 micelles showed that an increase in disease severity correlated with a more robust response to therapy in VSMCs. Notably, miR-145 micelle therapy rescued contractile marker expression to baseline contractile levels in VSMCs derived from the most severely diseased tissues. As such, we demonstrate the use of miR-145 micelles across different stages of atherosclerosis disease and present further evidence of the translatability of miR-145 micelle treatment for atherosclerosis.

Thoracic endovascular aortic repair (TEVAR) is a commonly performed operation for patients with type B aortic dissection (TBAD). The goal of TEVAR is to cover the proximal entry tear between the true lumen (TL) and the false lumen (FL) with an endograft to induce FL thrombosis, allow for aortic healing, and decrease the risk of aortic aneurysm and rupture. While TEVAR has shown promising outcomes, it can also result in devastating complications including stroke, spinal cord ischemia resulting in paralysis, as well as long-term heart failure, so treatment remains controversial. Similarly, the biomechanical impact of aortic endograft implantation and the hemodynamic impact of endograft design parameters such as length are not well-understood. In this study, a fluid-structure interaction (FSI) computational fluid dynamics (CFD) approach was used based on the immersed boundary and Lattice-Boltzmann method to investigate the association between the endograft length and hemodynamic variables inside the TL and FL. The physiological accuracy of the model was evaluated by comparing simulation results with the true pressure waveform measurements taken during a live TEVAR operation for TBAD. The results demonstrate a non-linear trend towards increased FL flow reversal as the endograft length increases but also increased left ventricular pulsatile workload. These findings suggest a medium-length endograft may be optimal by achieving FL flow reversal and thus FL thrombosis, while minimizing the extra load on the left ventricle. These results also verify that a reduction in heart rate with medical therapy contributes favorably to FL flow reversal.

IMPORTANCE:The use of statins in patients with symptomatic peripheral artery disease remains suboptimal despite strong clinical practice guideline recommendations; however, it is unknown whether rates are associated with substantial improvements after lower extremity revascularization. OBJECTIVE:To report longitudinal trends of statin use in patients with peripheral artery disease undergoing lower extremity revascularization and to identify the clinical and procedural characteristics associated with prescriptions for new statin therapy at discharge. DESIGN, SETTING, AND PARTICIPANTS:This was a retrospective cross-sectional study using data from the Vascular Quality Initiative registry of patients who underwent lower extremity peripheral artery disease revascularization from January 1, 2014, through December 31, 2019. The Vascular Quality Initiative is a multicenter registry database including academic and community-based hospitals throughout the US. Patients aged 18 years or older undergoing lower extremity revascularization with available statin data (preprocedure and postprocedure) were included. Those not receiving statin therapy for medical reasons were excluded from final analyses. EXPOSURES:Patients undergoing lower extremity revascularization for whom statin therapy is indicated. MAIN OUTCOMES AND MEASURES:Multivariate logistic regression was used to determine the clinical and procedural characteristics associated with new statin prescription for patients not already taking a statin preprocedure. The overall rates of statin prescription as well as rates of new statin prescription at discharge were determined. In addition, the clinical, demographic, and procedural characteristics associated with new statin prescription were analyzed. RESULTS:There were 172 025 procedures corresponding to 125 791 patients (mean [SD] age, 67.7 [11.0] years; 107 800 men [62.7%]; and 135 405 White [78.7%]) included in the analysis. Overall rates of statin prescription at discharge improved from 17 299 of 23 093 (75%) in 2014 to 29 804 of 34 231 (87%) in 2019. However, only 12 790 of 42 020 patients (30%) not already taking a statin at the time of revascularization during the study period were newly discharged with a statin medication. New statin prescription rates were substantially lower after endovascular intervention (7745 of 29 581 [26%]) than after lower extremity bypass (5045 of 12 439 [41%]). Body mass index of 30 or greater (odds ratio [OR], 1.13; 95% CI, 1.04-1.24; P < .001), diabetes (diet-controlled vs no diabetes, OR, 1.22; 95% CI, 1.05-1.41; P = .01), smoking (current vs never, OR, 1.32; 95% CI, 1.21-1.45; P < .001), hypertension (OR, 1.19; 95% CI, 1.09-1.29; P < .001), and coronary heart disease (OR, 1.26; 95% CI, 1.17-1.35; P < .001) were associated with an increased likelihood of new statin prescription after endovascular intervention, whereas female sex, older age, antiplatelet use, and prior peripheral revascularization were associated with a decreased likelihood. CONCLUSIONS AND RELEVANCE:In this cross-sectional study, although statin use was associated with a substantial improvement after lower extremity revascularization, more than two-thirds of patients not already taking a statin preprocedure remained not taking a statin at discharge. Further investigations to understand the clinical implications of these findings and develop clinician- and system-based interventions are needed.

OBJECTIVE:Traumatic popliteal artery injuries are associated with the greatest risk of limb loss of all peripheral vascular injuries, with amputation rates of 10% to 15%. The purpose of the present study was to examine the outcomes of patients who had undergone operative repair for traumatic popliteal arterial injuries and identify the factors independently associated with limb loss. METHODS:A multi-institutional retrospective review of all patients with traumatic popliteal artery injuries from 2007 to 2018 was performed. All the patients who had undergone operative repair of popliteal arterial injuries were included in the present analysis. The patients who had required a major lower extremity amputation (transtibial or transfemoral) were compared with those with successful limb salvage at the last follow-up. The significant predictors (P < .05) for amputation on univariate analysis were included in a multivariable analysis. RESULTS:A total of 302 patients from 11 institutions were included in the present analysis. The median age was 32 years (interquartile range, 21-40 years), and 79% were men. The median follow-up was 72 days (interquartile range, 20-366 days). The overall major amputation rate was 13%. Primary repair had been performed in 17% of patients, patch repair in 2%, and interposition or bypass in 81%. One patient had undergone endovascular repair with stenting. The overall 1-year primary patency was 89%. Of the patients who had lost primary patency, 46% ultimately required major amputation. Early loss (within 30 days postoperatively) of primary patency was five times more frequent for the patients who had subsequently required amputation. On multivariate regression, the significant perioperative factors independently associated with major amputation included the initial POPSAVEIT (popliteal scoring assessment for vascular extremity injury in trauma) score, loss of primary patency, absence of detectable immediate postoperative pedal Doppler signals, and lack of postoperative antiplatelet therapy. Concomitant popliteal vein injury, popliteal injury location (P1, P2, P3), injury severity score, and tibial vs popliteal distal bypass target were not independently associated with amputation. CONCLUSIONS:Traumatic popliteal artery injuries are associated with a significant rate of major amputation. The preoperative POPSAVEIT score remained independently associated with amputation after including the perioperative factors. The lack of postoperative pedal Doppler signals and loss of primary patency were highly associated with major amputation. The use of postoperative antiplatelet therapy was inversely associated with amputation, perhaps indicating a protective effect.

OBJECTIVE:Endovascular abdominal aortic repair can involve the incorporation of renal arteries. Revascularization after intentional or unintentional renal artery (RA) coverage is not always technically successful, and the loss of a single RA may result in the need for postoperative dialysis. Thus, we compared the outcomes after endovascular aneurysm repair (EVAR) stratified by RA involvement (RAI). METHODS:Patient data from the Vascular Quality Initiative from 2009 to 2018 registry were analyzed. The exclusion criteria were preoperative dialysis, missing RAI data, and repair above the superior mesenteric artery. The repair type cohorts were defined as (1) no RAI (NRAI), (2) RAI with revascularization (RAI-R), and (3) RAI with no revascularization (RAI-NR). A sensitivity analysis was performed by excluding ruptured presentations. The primary outcome was the need for postoperative dialysis. The secondary outcomes were 30-day mortality, dialysis at follow-up, postoperative renal function, and 2-year survival. Multivariate analysis was used to determine the independent predictors for postoperative dialysis. The 2-year survival analysis was performed using Kaplan-Meier log-rank test. RESULTS:Of 54,020 patients in the EVAR and TEVAR (thoracic EVAR)/complex EVAR modules in the Vascular Quality Initiative, 25,724 met the criteria for inclusion (NRAI, n = 24,879; RAI-R, n = 733; RAI-NR, n = 112). The demographics and comorbidities were similar among the three groups. The RAI-NR group had more frequently had ruptured or symptomatic aneurysms. The postoperative dialysis requirement was higher in the RAI-NR group (NRAI, 0.7%; RAI-R, 2.2%; RAI-NR, 17%; P < .0001), as were the 30-day mortality and dialysis requirement at follow-up. On multivariate analysis, RAI-R (odds ratio [OR], 2.2; P = .03) and RAI-NR (OR, 5.9; P < .0001) were independent predictors of postoperative dialysis and remained so after excluding ruptured presentations (RAI-R: OR, 3; P = .003; RAI-NR: OR, 22.3; P < .0001). Other independent predictors of the need for postoperative dialysis were worse preoperative renal function, a symptomatic presentation, any preoperative or intraoperative blood transfusion, and larger blood loss (≥200 mL). Excluding those with rupture, the overall survival at 2 years on Kaplan-Meier analysis was lower for the RAI-NR group (NRAI, 92%; RAI-R, 89%; RAI-NR, 80%; P = .004). CONCLUSIONS:RAI is highly predictive of the need for postoperative and permanent dialysis after EVAR. RAI-NR was associated with lower overall survival. These risks should be considered when planning and performing EVAR and should be weighed against the risks of open repair when considering the treatment options.

OBJECTIVE:Aortic dissection can result in devastating cerebral, visceral, renal, spinal, and extremity ischemia. We describe the management and outcomes of patients presenting with aortic dissection and lower extremity malperfusion (LEM). METHODS:A single-center institutional aortic database was queried for patients with aortic dissection and LEM from 2011 to 2019. The primary end point was resolution of LEM after aortic repair. Secondary end points were amputation, in-hospital mortality, time to intervention, and postoperative complications. RESULTS:Of 769 patients with aortic dissection, 42 (5.5%) presented acutely with LEM: 16 with Stanford type A and 26 Stanford type B aortic dissection (age 55 ± 13 years; 90% men). Most presented as Rutherford IIB symptoms, but patients with type A had Rutherford III more often, compared with those with type B. Aortic repair was performed before limb interventions in 36 patients (86%; 19 TEVAR, 16 open arch and ascending repair, and 1 open descending aortic repair with fenestration). Seven (19%) had immediate failure with persistent malperfusion recognized in the operating room and underwent additional limb intervention, including extra-anatomic revascularization (n = 4), iliac stenting (n = 2), and femoral patch with septal fenestration or tacking (n = 2). Three patients (8%) had early delayed failure requiring extra-anatomic bypass in two and amputation in one. In contrast, six patients had limb-first intervention with extra-anatomic revascularization. None had immediate failure, but one-half had early delayed failure requiring proximal aortic intervention: two TEVAR and one open aortic fenestration. Limb-first patients were more likely to have early delayed failure compared with aortic dissection treated first patients (50% vs 8%; P = .029). The amputation rate was 2%, occurring in one type A patient. The overall in-hospital mortality was 7% (n = 3), with no difference between type A and type B aortic dissection. There was no difference in surgical site infection, postoperative dialysis need, stroke, and myocardial infarction. CONCLUSIONS:In patients presenting with acute aortic dissection with limb ischemia, resolution of the malperfusion occurs in the majority of cases after primary aortic dissection intervention, emphasizing the usefulness of urgent TEVAR for complicated type B and open repair of type A before lower extremity intervention. Limb-first interventions have a higher early delayed failure rate and thus require more frequent reoperation. However, the overall amputation rate in LEM owing to aortic dissection remains low.

Patients presenting with hemodynamic instability associated with pelvic fractures continue to have very high mortality and surgeons continue to seek damage control strategies that may improve survival. Strategies usually require massive transfusion, immediate pelvic stabilization and another adjunctive maneuver's such as angioembolization or preperitoneal pelvic packing to prevent hemorrhagic death. One current intervention that has regained some popularity in lieu of resuscitative thoracotomy is the Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA). This requires some manner of femoral arterial access to insert a balloon into the aorta and increase central blood pressure (cardiac and cerebral perfusion) and control active pelvic bleeding. Based on several animal models and an increasing number of publications, many US level I trauma centers have now opted to use REBOA in carefully selected patients showing signs of near cardiac arrest from non-compressible torso hemorrhage. Description of the current advances in aortic occlusion using catheter-based technology in the setting of severe shock for non-compressible torso hemorrhage from pelvic ring fracture is the purpose of this report.

PURPOSE/OBJECTIVE:There have been increasing number of endovascular aortic aneurysm repair performed in hostile necks using newer generation technology including polymer-based proximal sealing devices such as the Ovation system. Unique design features of the device can pose challenges during endovascular salvage of type 1A endoleak. We describe two cases of successful application of physician-modified fenestrated endografting, in order to repair type 1A endoleaks following endovascular aortic aneurysm repair with ovation system. TECHNIQUE/METHODS:In both cases, multi-fenestrated endografts were custom-modified using preloaded wire technique on Cook Zenith Alpha thoracic stent grafts at the back table. Under general anesthesia, left brachial cut down and a single percutaneous femoral access were performed. Staggered deployment of fenestrated endograft, accompanied by sequential catheterization of target vessels, facilitated correct alignment of fenestrated endograft. Infolding of fenestrated endograft inside the Ovation main body resulted in leg claudication, and repaired with balloon expandable covered tent. Prophylactic deployment of balloon expandable covered stent was performed in the second case. Both cases showed resolution of type 1A endoleak. CONCLUSION/CONCLUSIONS:Fenestrated endovascular repair is feasible for proximal failure of Ovation endografts. Careful planning and advanced skill set in complex endovascular aortic repair are required, as well as detailed knowledge of the failed endografts.