Joy Walker

Type II endoleak with or without intervention after endovascular aortic aneurysm repair does not change aneurysm-related outcomes despite sac growth

OBJECTIVE There is considerable controversy about the significance and appropriate treatment of type II endoleaks (T2Ls) after endovascular aneurysm repair (EVAR). We report our long-term experience with T2L management in a large multicenter registry. METHODS Between 2000 and 2010, 1736 patients underwent EVAR, and we recorded the incidence of T2L. Primary outcomes were mortality and aneurysm-related mortality (ARM). Secondary outcomes were change in aneurysm sac size, major adverse events, and reintervention. RESULTS During the follow-up (median of 32.2 months; interquartile range, 14.2-52.8 months), T2L was identified in 474 patients (27.3%). There were no late abdominal aortic aneurysm ruptures attributable to a T2L. Overall mortality (P = .47) and ARM (P = .26) did not differ between patients with and without T2L. Sac growth (median, 5 mm; interquartile range, 2-10 mm) was seen in 213 (44.9%) of the patients with T2L. Of these patients with a T2L and sac growth, 36 (16.9%) had an additional type of endoleak. Of all patients with T2L, 111 (23.4%) received reinterventions, including 39 patients who underwent multiple procedures; 74% of the reinterventions were performed in patients with sac growth. Reinterventions included lumbar embolization in 66 patients (59.5%), placement of additional stents in 48 (43.2%), open surgical revision in 14 (12.6%), and direct sac injection in 22 (19.8%). The reintervention was successful in 35 patients (31.5%). After patients with other types of endoleak were excluded, no difference in overall all-cause mortality (P = .57) or ARM (P = .09) was observed between patients with T2L-associated sac growth who underwent reintervention and those in whom T2L was left untreated. CONCLUSIONS In our multicenter EVAR registry, overall all-cause mortality and ARM were unaffected by the presence of a T2L. Moreover, patients who were simply observed for T2L-associated sac growth had aneurysm-related outcomes similar to those in patients who underwent reintervention. Our future work will investigate the most cost-effective ways to select patients for intervention besides sac growth alone.

Safety and feasibility of adjunctive dexamethasone infusion into the adventitia of the femoropopliteal artery following endovascular revascularization

OBJECTIVE Restenosis following endovascular treatment of the femoropopliteal segment is associated with the inflammatory response produced in the artery wall at the time of the procedure. Although local drug delivery to the superficial femoral and popliteal arteries promises improved patency, data are currently limited. We hypothesized that improved percutaneous delivery of an anti-inflammatory compound into the adventitia of the femoropopliteal at the time of endovascular treatment would be safe, feasible, and decrease the inflammatory response. METHODS This was a prospective, investigator-initiated, phase I, first-in-man study testing the safety and feasibility of percutaneous adventitial delivery of dexamethasone. Following successful intervention, an adventitial microinfusion catheter was advanced over a 0.014-inch wire to the treated segment. Its microneedle (0.9 mm long × 140-μm diameter) was deployed into the adventitia to deliver dexamethasone (4 mg/mL) mixed with contrast agent (80:20 ratio), providing fluoroscopic visualization. The primary safety outcome measure was freedom from vessel dissection, thrombosis, or extravasation while the primary efficacy outcome was duplex-determined binary restenosis defined as a peak systolic velocity ratio >2.5. RESULTS Twenty patients with Rutherford clinical category 2-5 enrolled in this study. The mean age was 66, and 55% had diabetes mellitus. Treated lesion length was 8.9 ± 5.3 cm, and 50% were chronic total occlusions. Eighty percent of treated lesions were in the distal superficial femoral or popliteal arteries. All lesions were treated by balloon angioplasty with provisional stenting (n = 6) for suboptimal result. Three patients were treated with atherectomy as well. A mean of 1.6 ± 1.1 mg (0.5 ± 0.3 mL) of dexamethasone sodium phosphate was injected per centimeter of lesion length. In total, a mean of 12.1 ± 6.1 mg of dexamethasone was injected per patient. The mean number of injections required per lesion was 3.0 ± 1.3 cm, minimum one and maximum six injections. There was 100% technical success of drug delivery and no procedural or drug-related adverse events. The mean Rutherford score decreased from 3.1 ± .7 (median, 3.0) preoperatively to .5 ± .7 at 6 months (median, 0.0; P < .00001). Over this same time interval, the index leg ankle-brachial index increased from .68 ± .15 to .89 ± .19 (P = .0003). The preoperative C-reactive protein in this study was 6.9 ± 8.5 indicating severe baseline inflammation, which increased to 14.0 ± 23.1 mg/L (103% increase) at 24 hours following the procedure. However, this increase did not reach statistical significance of P = .14. Two patients met the primary efficacy end point of loss of primary patency by reoccluding their treated segment of the index lesion during the follow-up period. CONCLUSIONS Adventitial drug delivery via a microinfusion catheter is a safe and feasible alternative to intimal-based methods for adjunctive treatment in the femoropopliteal segment. The 6-month preliminary results suggest perivascular dexamethasone treatment may improve outcomes following angioplasty to the femoral and popliteal arteries, and support further clinical investigation of this approach.

Adherence to endovascular aortic aneurysm repair device instructions for use guidelines has no impact on outcomes.

OBJECTIVE Prior reports have suggested unfavorable outcomes after endovascular aortic aneurysm repair (EVAR) performed outside of the recommended instructions for use (IFU) guidelines. We report our long-term EVAR experience in a large multicenter registry with regard to adherence to IFU guidelines. METHODS Between 2000 and 2010, 489 of 1736 patients who underwent EVAR had preoperative anatomic measurements obtained from the M2S, Inc, imaging database (West Lebanon, NH). We examined outcomes in these patients with regard to whether they had met the device-specific IFU criteria. Primary outcomes were all-cause mortality and aneurysm-related mortality. Secondary outcomes were endoleak status, adverse events, reintervention, and aneurysm sac size change. RESULTS The median follow-up for the 489 patients was 3.1 years (interquartile range, 1.6-5.0 years); 58.1% (n = 284) had EVAR performed within IFU guidelines (IFU-adherent group), and 41.9% (n = 205) had EVAR performed outside of IFU guidelines (IFU-nonadherent group). Preoperative anatomic data showed that 62.4% of the IFU-nonadherent group had short neck length, 10.2% had greater angulation than recommended, 7.3% did not meet neck diameter criteria, and 20% had multiple anatomic issues. A small portion (n = 49; 10%) of the 489 patients were lost to follow-up because of leaving membership enrollment (n = 28), moving outside the region (n = 10), or discontinuing image surveillance (n = 11). There was no significant difference in any of the primary or secondary outcomes between the IFU-adherent and IFU-nonadherent groups. Aneurysm sac size change at any time point during follow-up also did not differ significantly between the two groups. A Cox proportional hazard model showed that IFU nonadherence was not predictive of all-cause mortality (hazard ratio, 1.0; P = .91). Similarly, IFU nonadherence was not identified as a risk factor for aneurysm-related mortality or adverse events in stepwise Cox proportional hazards models. CONCLUSIONS In our cohort of EVAR patients with detailed preoperative anatomic information and long-term follow-up, overall mortality and aneurysm-related mortality were unaffected by IFU adherence. In addition, rates of endoleak and reintervention after initial EVAR were similar, suggesting that lack of IFU-based anatomic suitability was not a driver of outcomes.

Ferumoxytol-Enhanced Magnetic Resonance Angiography is a Feasible Method for the Clinical Evaluation of Lower Extremity Arterial Disease

BACKGROUND Renal toxicity from conventional, iodinated, intravenous contrast agents is a common complication in patients with peripheral artery disease (PAD). Similarly, the potential for serious side effects prevents the use of gadolinium-based agents in many patients with depressed renal function. Ferumoxytol-enhanced magnetic resonance angiography (Fe-MRA) is a novel technique that uses an intravenous, ultrasmall, superparamagnetic, iron oxide preparation, currently approved by the Food and Drug Administration for the treatment of iron deficiency anemia in adults with chronic kidney disease. Our objective was to determine the feasibility of Fe-MRA for clinical decision making in PAD patients. METHODS This was a prospective pilot study assessing 10 patients with suspected arterial occlusive disease with contrast-enhanced MRA of the aorta and lower extremities. Of those, 5 had renal insufficiency and were imaged with Fe-MRA, whereas the remainder underwent gadolinium-enhanced MRA. Qualitative and quantitative evaluations of deidentified images at each arterial station were independently performed by 4 blinded vascular surgeons. RESULTS All patients were men, with an average age of 68 ± 4 years. The 2 groups had similar incidences of diabetes, hypertension, hyperlipidemia, and coronary artery disease. Patients undergoing Fe-MRA had significantly decreased renal function (estimated glomerular filtration rate, 35.4 vs. 77.6; P = 0.02). There were no adverse events during contrast administration in either group. No difference was found in the overall quality of the ferumoxytol versus the gadolinium studies (7.1 ± 2.0 vs. 7.4 ± 2.4, P = 0.67). Similarly, reviewers felt comfortable basing clinical decisions on the images 89% of the time with both the ferumoxytol and gadolinium groups (P = 1.00). CONCLUSIONS This is the first report of an important alternative to conventional computed tomography angiography and MRA in PAD patients, particularly in the setting of renal insufficiency. Fe-MRA provides a useful tool in patients with suspected lower extremity PAD without the potential risks of gadolinium.

Adventitial Nab-Rapamycin Injection Reduces Porcine Femoral Artery Luminal Stenosis Induced by Balloon Angioplasty via Inhibition of Medial Proliferation and Adventitial Inflammation

Background—Endovascular interventions on peripheral arteries are limited by high rates of restenosis. Our hypothesis was that adventitial injection of rapamycin nanoparticles would be safe and reduce luminal stenosis in a porcine femoral artery balloon angioplasty model. Methods and Results—Eighteen juvenile male crossbred swine were included. Single-injury (40%–60% femoral artery balloon overstretch injury; n=2) and double-injury models (endothelial denudation injury 2 weeks before a 20%–30% overstretch injury; n=2) were compared. The double-injury model produced significantly more luminal stenosis at 28 days, P=0.002, and no difference in medial fibrosis or inflammation. Four pigs were randomized to the double-injury model and adventitial injection of saline (n=2) or 500 &mgr;g of nanoparticle albumin-bound rapamycin (nab-rapamycin; n=2) with an endovascular microinfusion catheter. There was 100% procedural success and no difference in endothelial regeneration. At 28 days, nab-rapamycin led to significant reductions in luminal stenosis, 17% (interquartile range, 12%–35%) versus 10% (interquartile range, 8.3%–14%), P=0.001, medial cell proliferation, P<0.001, and fibrosis, P<0.001. There were significantly fewer adventitial leukocytes at 3 days, P<0.001, but no difference at 28 days. Pharmacokinetic analysis (single-injury model) found rapamycin concentrations 1500× higher in perivascular tissues than in blood at 1 hour. Perivascular rapamycin persisted ≥8 days and was not detectable at 28 days. Conclusions—Adventitial nab-rapamycin injection was safe and significantly reduced luminal stenosis in a porcine femoral artery balloon angioplasty model. Observed reductions in early adventitial leukocyte infiltration and late medial cell proliferation and fibrosis suggest an immunosuppressive and antiproliferative mechanism. An intraluminal microinfusion catheter for adventitial injection represents an alternative to stent- or balloon-based local drug delivery.

Two Distinct Isoforms of Matrix Metalloproteinase-2 Are Associated with Human Delayed Kidney Graft Function

Delayed graft function (DGF) is a frequent complication of renal transplantation, particularly in the setting of transplantation of kidneys derived from deceased donors and expanded-criteria donors. DGF results from tubular epithelial cell injury and has immediate and long term consequences. These include requirement for post-transplantation dialysis, increased incidence of acute rejection, and poorer long-term outcomes. DGF represents one of the clearest clinical examples of renal acute ischemia/reperfusion injury. Experimental studies have demonstrated that ischemia/reperfusion injury induces the synthesis of the full length secreted isoform of matrix metalloproteinase-2 (FL-MMP-2), as well as an intracellular N-terminal truncated MMP-2 isoform (NTT-MMP-2) that initiates an innate immune response. We hypothesized that the two MMP-2 isoforms mediate tubular epithelial cell injury in DGF. Archival renal biopsy sections from 10 protocol biopsy controls and 41 cases with a clinical diagnosis of DGF were analyzed for the extent of tubular injury, expression of the FL-MMP-2 and NTT-MMP-2 isoforms by immunohistochemistry (IHC), in situ hybridization, and qPCR to determine isoform abundance. Differences in transcript abundance were related to tubular injury score. Markers of MMP-2-mediated injury included TUNEL staining and assessment of peritubular capillary density. There was a clear relationship between tubular epithelial cell expression of both FL-MMP-2 and NTT-MMP-2 IHC with the extent of tubular injury. The MMP-2 isoforms were detected in the same tubular segments and were present at sites of tubular injury. qPCR demonstrated highly significant increases in both the FL-MMP-2 and NTT-MMP-2 transcripts. Statistical analysis revealed highly significant associations between FL-MMP-2 and NTT-MMP-2 transcript abundance and the extent of tubular injury, with NTT-MMP-2 having the strongest association. We conclude that two distinct MMP-2 isoforms are associated with tubular injury in DGF and offer novel therapeutic targets for the prevention of this disorder.

Diagnosis and management of peripheral artery disease in women.

Peripheral artery disease (PAD) is a significant cause of morbidity and mortality in the USA. Not only is it a major cause of functional impairment and limb loss, but it is also strongly associated with an increased risk of myocardial infarction, stroke, and death. Large population studies have demonstrated high rates of PAD in women, but this is not widely recognized by the public or by clinicians. One potential reason for this is that women with PAD are more likely than men to be asymptomatic or have atypical symptoms. In addition, women with PAD experience higher rates of functional decline and may have poorer outcomes after surgical treatment for PAD compared with men. Currently, it is not known if there are sex-specific differences in risk factors for the onset, progression, and surgical outcomes of PAD. This review will focus on the diagnosis and management of PAD in women and examine sex-specific differences in the prevalence, risk factors, presentation, and outcomes of this disease.

Utility of Preoperative Non-Contrast Computed Tomography (CT) to Guide Perioperative Management for Renal Transplantation

Background Peripheral artery disease is highly prevalent among patients with end stage renal disease. Non-contrast CT scans of the abdomen and pelvis (CT A/P) are performed for pre-transplant (tx) evaluation in patients at high risk for cardiovascular events. The purpose of this study is to examine the severity and distribution of common iliac artery (CIA) and external iliac artery (EIA) calcifications and the associations with operative complications and clinical outcomes following renal tx. Methods Retrospective analysis of 202 renal tx recipients between 2/2013-11/2014 who underwent pre-operative CT A/P within 3 years of their surgery. All CT scans were assessed using a previously described scoring system (Table 1). Results The mean age was 57.2±11.2 years and 132/202 (65%) were men. 189/202 (94%) had hypertension, 124/202 (61%) had diabetes mellitus (DM), and 77/202 (38%) had coronary artery disease (CAD). There was no significant difference in calcification scores between sides (Table 2). In a regression analysis, previous cerebrovascular accident (CVA) (OR 5.43, p=0.03), CAD (OR 3.56, p<0.001), history of smoking (OR 2.08, p=0.02), DM (OR 2.23, p=0.01), and older age (OR 1.10, p<0.001) were significantly associated with moderate/severe CIA plaque (morphology score ≥ 2). One patient could not undergo tx due to severe, diffuse calcifications. 7 patients required arterial reconstruction during renal tx, all of whom had tx to the right EIA. Patients with moderate/severe right EIA plaque were more likely to require arterial reconstruction compared to those with none/mild plaque (4/34 [11.7%] v. 3/130 [2.3%]; p=0.03). There were 58 cases of delayed graft function (DGF), 51 of which occurred in transplants to the right EIA. In these cases, DGF was significantly associated with moderate/severe right EIA plaque (OR 2.82, p=0.009). Post-operative cardiac events occurred in 17/201 (8.5%) patients. In a multivariable logistic regression model, history of CAD (OR 3.79, p=0.03), congestive heart failure (OR 5.54, p=0.009), and severe CIA plaque (morphology score=3) (OR 4.98, p=0.04) were significantly associated with post-operative cardiac complications. 21 patients died during a mean follow-up of 1153 ± 1784 days. In a multivariable model, DM (p=0.05) and previous CVA (p=0.02) were significantly associated with increased risk of death. Conclusions Local calcified plaque of the recipient iliac artery is associated with increased operative complexity and higher rates of DGF. Plaque burden in the CIA is associated with both patient demographic factors and post-operative cardiac events, and is likely indicative of a greater severity of systemic atherosclerotic disease. Routine pre-tx CT scans in high risk patients may guide operative strategy and facilitate perioperative management to improve clinical outcomes. Table. No title available. Table. No title available. Research reported in this publication was supported in part by an NIAID T32 training grant from the National Institutes of Health under an award to the University of California, San Francisco (T32AI125222). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Lower Extremity Revascularization in the Medicare Population: The Ongoing Rise of Office-Based Atherectomy

cost-effective. The aim of this study was to evaluate the cost-effectiveness of performing repeated interventions vs starting a new AVF. Methods: We reviewed all patients with mature radiocephalic, brachiocephalic, and brachiobasilic AVFs at a single academic institution between 2000 and 2016 and assessed open and percutaneous interventions to maintain functional patency after the fistula was created. These data were used to parameterize a Markov simulation model to determine the cost-effectiveness for performing an open or percutaneous intervention vs creating an AVF at a new anatomic location. This model compared strategies of creating a new AVF after the first to fourth reintervention within a 1-year time window, with the reference being creation of a new AVF on the fourth reintervention. We used this model to calculate incremental cost-effectiveness ratios (ICERs) using 2016 costs from Medicare’s payer-perspective per quality-adjusted life-year (QALY) gained. Results: A total of 720 mature AVFs were created during the 15-year period, and 283 (39%) underwent at least one intervention to maintain functional patency, with the median (interquartile range) time to first reintervention of 12.6 (10-17) months. For the strategies of creating a new AVF after the first vs the fourth reintervention, costs ranged from

Early and delayed rupture after endovascular abdominal aortic aneurysm repair in a 10-year multicenter registry.

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