Citations

Introduction: Five randomized trials proving the efficacy and safety of mechanical embolectomy for ischemic stroke patients used differing radiological methods to select patients for treatment. Hypothesis: The percentage of patients evaluated in a non-clinical trial setting that would meet radiological criteria to be included in the five trials will differ substantially. Methods: Retrospective study of consecutive ischemic stroke patients who were considered for endovascular stroke therapy based on confirmed intracranial large vessel occlusion (M1, M2, or carotid terminus) at an academic medical center from April 2010 - November 2014. All patients underwent CT perfusion and CT angiogram. Results: The table shows baseline characteristics of 119 patients. Median age was 69 years (IQR 57-79) and median NIHSS 18 (IQR 14-21). Most patients had ASPECTS score ≥ 6 (n=105, 88.2%). The M1 segment of MCA was the most common vessel occluded (n=81, 68%). All 119 patients (100%) met radiological criteria for MR CLEAN while 105 (88.2%) met criteria for SWIFT-PRIME, 96 (80.7%) for REVASCAT, 80/116 (69.0%) for EXTEND IA, and 74 (62.2%) for ESCAPE. IV TPA was given to 58 patients (48.7%) and acute endovascular stroke therapy attempted in 66 (55.5%). Any intracranial hemorrhage was more common in the patients treated with endovascular therapy than in those who were not (36% vs. 17%, p=0.025). The frequency of symptomatic ICH did not significantly differ between these two groups (6.1% vs 3.8%, p=0.691). Conclusions: The percentage of patients with acute stroke and large vessel occlusion that would qualify for endovascular stroke trials based on radiological criteria varies considerably (62%-100%) in a non-clinical trial cohort from an academic comprehensive stroke center. Additional individual patient characteristics influence treatment decisions in non-clinical trial settings.

Background: Noninvasive fractional flow measures with CT angiography (CTA) have revolutionized cardiology, yet the complex anatomy of the cerebral circulation and boundary conditions challenge the study of intracranial atherosclerosis. We developed a framework for systematic computational fluid dynamics (CFD) of middle cerebral artery (MCA) stenosis with CTA in SAMMPRIS. Methods: A 3D geometric mesh was generated from CTA source images, followed by CFD processing in Ansys (ICEM, CFX) on a Cray supercomputer. Reference boundary conditions were applied with an ICA inlet and outlets at the ACA and distal MCA to yield quantitative maps of intraluminal pressure drops (ΔP or fractional flow), blood flow velocity (V) and turbulent kinetic energy (TKE) with wall shear stress (WSS) mapped along the arteries. CFD parameters were then compared with SAMMPRIS angiography variables. Results: Of 451 SAMMPRIS (70-99% symptomatic stenosis) subjects, CTA was acquired at enrollment in 41 MCA cases. CFD results were successfully attained in 30, limited by anatomy (e.g. across branch points) in 7/11 and poor CTA resolution in 4/11. Fractional flow (ΔP) across stenosis was mean 0.64 ± SD 0.33, with maximal stenosis velocity of mean 192 ± SD 101 cm/s and maximal WSS 0.36 ± SD 0.25 mm Hg. SAMMPRIS angiography percent stenosis was unrelated to ΔP -0.163 (p=0.399), velocity 0.126 (p=0.514) or WSS 0.078 (p=0.689). Worse collateral blood flow grades were associated with larger ΔP (p=0.137), higher velocity (p=0.059), higher WSS (p=0.112). Asymmetric WSS with high and low regions on opposing arterial walls was measured in the post-stenotic segment in 25/30 (83%). TKE maps revealed focal increases in the post-stenotic region, yet not above abnormal thresholds based on arterial diameter. Conclusions: CTA CFD of intracranial atherosclerosis provides detailed noninvasive measures of hemodynamics.

Background: Collateral blood flow, modulated by inflammation and arteriogenesis, alters ischemic injury in intracranial atherosclerosis. We investigated the potential link between several inflammatory and arteriogenic biomarkers with angiographic findings at enrollment in BIOSIS/SAMMPRIS. Methods: Baseline angiography and blood biomarkers of BIOSIS/SAMMPRIS, which included subjects with stroke or TIA due to 70-99% intracranial stenosis were analyzed. Collateral blood flow status at angiography was categorized by the combination of antegrade flow (TICI) and corresponding extent of collaterals (ASITN/SIR). Collateral status was analyzed with respect to blood progenitor cell markers (CD34) at baseline and inflammatory biomarkers (Plasminogen Activator Inhibitor-1 (PAI-1), E-selectin, high sensitivity C-reactive protein (hsCRP) and Lipoprotein-associated phospholipase A2 (Lp-PLA 2 ) activity and concentrations) at baseline, 30 days and 4 months. Results: 376 subjects (mean age 60.44 years SD 11; 149/376 (39.6%) women) enrolled in BIOSIS/SAMMPRIS had angiography of collaterals and biomarker data. Collateral perfusion was impaired in 71 (19%) and intermediate in 188 (50%), with robust collaterals in 117 (30%) subjects. Better collateral status was associated with younger age (p=0.001), male sex (p=0.029) and greater baseline physical activity (p=0.007). Baseline blood progenitor cell (CD34+) counts were unrelated to angiographic features at enrollment, whereas inflammatory Lp-PLA 2 activity was linked (p=0.059) with blood flow categories, and lower hsCRP (p=0.025) with better collaterals. Lp-PLA 2 activity was lowest in those with robust collaterals at 30 days (p=0.070) and 4 months (p=0.120). Those with robust collaterals had the greatest decrease in Lp-PLA 2 activity (p=0.021) and concentration (p=0.027) by 30 days, with a continued decline of Lp-PLA 2 activity (p=0.037) to 4 months. Disparate trends in inflammatory markers were seen in the medical and stenting arms. Conclusions: Inflammatory biomarkers are linked with collateral blood flow status in intracranial atherosclerosis. The impact of physical activity, medications and other therapeutic investigations may disclose important mechanisms to avert ischemia.

Background and Purpose: The Hydrocoil Endovascular aneurysm occlusion and Packing Study (HELPS) was a randomized controlled trial comparing Hydrocoil to bare platinum coils . We performed a subgroup analysis of angiographic and clinical outcomes of medium sized aneurysms in the HELPS trial. Methods: We selected all patients with medium sized aneurysms (5mm-9.9mm) in the HELPS trial. The following outcomes were compared between the HydroCoil and control groups: 1) any recurrence, 2) major recurrence, 3) retreatment and 4) good neurological outcome defined as mRS≤2. Outcomes of recently ruptured and non-recently ruptured aneurysms were compared separately. Comparisons between groups were performed using Fisher’s exact test. A multivariate logistic regression analysis adjusting for aneurysm neck size, shape, use of adjunctive device and rupture status was performed. Results: A total of 288 patients with medium sized aneurysms were randomized (144 in each group). At 15-18 months post-treatment, major recurrence rate was significantly lower in the HydroCoil group than the control group (18.6% versus 30.8%, P=0.03, respectively). For recently ruptured aneurysm patients, major recurrence rate was significantly lower for HydroCoil than controls (20.3% versus 47.5%, P=0.003), while rates were similar between coil types for unruptured aneurysms (16.7% versus 14.8%, P=0.80). On multivariate analysis for patients with recently ruptured aneurysms, HydroCoil was associated with lower odds of any recurrence as compared to bare platinum (OR=0.37, 95%CI=0.18-0.76, P=0.006) and major recurrence (OR=0.27, 95%CI=0.12-0.58, P=0.0007). There was a trend towards lower retreatment rates in the recently ruptured group treated with HydroCoil (OR=0.00, 95%CI=0.00-2.01, P=0.12). Conclusion: For recently ruptured, medium sized aneurysms, as compared to bare platinum coils HydroCoils were associated with lower rates of major recurrence that were both statistically significant and clinically relevant. These findings suggest that HydroCoils should be the preferred treatment for this subset of patients.

Background: Flow diversion has been proposed as a valid option for patients with proximal internal carotid artery aneurysms. We analyzed a consecutive series of 38 patients with proximal (to the origin of the posterior communicating artery) internal carotid artery aneurysms treated with flow diversion over a 28-month interval. Methods: Clinical information and angiographic follow-up data were prospectively collected in a consecutive series of patients with proximal internal carotid artery aneurysms treated with flow diversion. No patients were lost to follow-up and every eligible patient (with at least 6 months of follow-up) underwent catheter angiography at 6 months. Results: The series include 38 patients (37 women and 1 man). Most of the aneurysms were large or giant and with a wide neck. In two patients, we failed to deliver the device to the target segment because of proximal vessel tortuosity; thus 36 patients underwent flow diversion. There were no permanent periprocedural neurological deficits. One patient experienced a transient neurological deficit and another patient suffered slight transient worsening of a third nerve paresis. Complete angiographic occlusion of the aneurysm was observed in 75% of patients at 6 months and in 87% of the eligible patients at one year. One patient was found to have asymptomatic internal carotid occlusion. Conclusion: Flow diversion is an effective and safe method to treat internal carotid artery aneurysms not amenable to other endovascular techniques.

Background and Purpose- It is important to know the costs for hospitalization for endovascular embolectomy patients so that comparisons can be made to payments to hospitals. Methods- Using the National Inpatient Sample, we evaluated the costs for hospitalization for patients treated with endovascular embolectomy in the United States from 2006-2008. The primary endpoint examined in this study was total hospital costs, and these were correlated with clinical outcome. Hospitalization costs were then compared with Medicare payments for their respective outcomes. MS-DRG 24 was the diagnostic related group code (DRG) for mechanical embolectomy with good outcome and MS-DRG 23 was the DRG code for mechanical embolectomy with major complications. Medicare payments were available at http://www.cms.hhs.gov . Results- A total of 3864 patients received endovascular embolectomy. 1649 patients were <65 years old and 2205 patients were ≥65 years old. Median hospital costs in 2008 dollars were $36,999 (IQR $26,662-$56,405) for patients with good outcome, $50,628 (IQR $33,135-$76,063) for patients with severe disability, and $35,109 (IQR $25,053-$62,621) for patients with mortality. Reimbursement in the year 2008 for DRG 24 (good outcome) was $22075 and reimbursement for DRG 23 (major complications) was $26639. Conclusions- Our study of the NIS shows that hospitalization costs in the United States for ischemic stroke patients treated with endovascular embolectomy are rather high, probably due to the serious nature of their illness. Medicare payments have not been adequate in reimbursing these hospitalizations. Further work is needed to ensure the future reconciliation of costs with payments.

Introduction: Heart transplantation is associated with prolonged survival and improved quality of life in patients with advanced cardiac disease albeit with an increased risk of malignancies due to the use of immunosuppressant medications. Our study aimed to determine the types and trends of in patients’ hospitalization for malignancies among heart transplant patients. Methods: We queried the 2005 to 2014 National Inpatient Sample(NIS) database to identify all patients with a history of heart transplant (ICD-9 codes V412, 99683) who were hospitalized with a diagnosis of cancer. The main outcome was the trend in cancer admissions. Secondary outcome were inpatient mortality, total charge and length of stay. Cochran’s and Mantel-Haenszel test was used to assess trends of cancer admissions. Adjusted OR were used to compare the incidence of death between the two groups. Results: A total of 36543(weighted national estimate of 177,604) patients were admitted with a history of heart transplantation over the study period, out of which 2347(6.4%) had a diagnosis of a malignancy. Cancer patients were older (Mean age 66±12 Vs. 61.1±18 P-Value <0.001) and were more likely to be male. There was an increasing trend in the rate of cancer admissions over the study period from 60 per 1000 patients in 2005 to 70 per 1000patients in 2014(P-Vale <0.0001). Overall the most prevalent cancer was Non-Hodgkin’s 20.9% followed by lung Cancer 19.1%. ninety-seven patients(4.1%) had a 2 or more cancers. Patients with a diagnosis of cancer were more likely to die while inpatients as compared those without a diagnosis of cancer (6.6% vs. 3.1%, adjusted OR 2.42 95%CI 1.53-3.38 P-value <0.001). Lastly, patients with cancer had an increased total median coast and a longer length of stay(Total charge(39735 vs, 32,035, P value =<0.001 and 5 vs. 4. P-value <0.001). Conclusion: Development of cancer among patients with a history of transplant adds significant morbidity and mortality. Further studies are needed to determine effective ways to reduce morbidity in this patient cohort.

Background: Poor collateral circulation and hypoperfusion may lead to recurrent stroke in intracranial atherosclerotic disease (ICAD). The role of perfusion in silent strokes and potentially insidious cognitive impairment in ICAD is unknown. We used evidence of impaired perfusion at angiography in SAMMPRIS to predict subsequent cognitive changes. Methods: Angiography at enrollment in the SAMMPRIS trial was independently evaluated, blind to clinical data and cognitive testing. Antegrade flow in the symptomatic arterial territory and corresponding collateral flow were scored. Impaired perfusion was defined by poor antegrade and poor collateral flow. Serial testing with the Montreal Cognitive Assessment (MoCA) was done in subjects without aphasia or neglect at baseline, 4 mo, 12 mo and closeout, or until subjects had a clinical stroke endpoint. Results: 207 subjects (median age 61, range 33-81 years; 37% women) had baseline MoCA scores with angiography data on territorial perfusion. Baseline MoCA scores (mean 24.2±4.1) were similar between categories of antegrade flow and collateral circulation. Impaired perfusion was noted in 33/207 (16%). Serial MoCA revealed that changes in cognition over time were different at 4 mo, 12 mo and closeout based on the presence of impaired perfusion at baseline (p<0.001). After more modest (mean MoCA change = 0.5 increase from baseline, p=0.80) early improved cognitive function at 4 mo, those with impaired perfusion had cognitive decline at 12 mo (mean MoCA change, p<0.01) unlike the continued improvement in other subjects. Cognitive changes in those with impaired perfusion were associated with a higher frequency of subsequent stroke in the territory. Conclusions: Impaired perfusion in the symptomatic arterial territory of ICAD predicts cognitive outcomes that may precede recurrent ischemia. Future studies may define the role of noninvasive perfusion imaging in ICAD to predict cognitive trajectories and recurrent stroke.

Purpose: Endovascular occlusion of aneurysms with the use of detachable platinum coils has proved to be a safe and durable alternative to the traditional surgical clipping. The aim of the present study is to understand the mechanism of apoptosis in aneurysm embolized with platinum coils using rabbit elastase‐induced aneurysm model. Materials & Methods: Elastase‐induced saccular aneurysms were created at the origin of right common carotid artery in thirty rabbits. Aneurysms were allowed to mature for 8 weeks then 20 aneurysms were embolized using platinum coils by endovascular means. Ten uncoiled aneurysms were used as controls. After 2 weeks (n=10) and 4 weeks (n=10) of implantation, aneurysm samples were harvested for apoptotic studies. Results: Expression of pro‐caspases‐3, ‐8 and ‐9 were elevated in coiled aneurysm embolized with platinum coils at both time points when compared with uncoiled aneurysm and control left carotid artery. Cleaved caspases‐3, ‐8 and ‐9 were found to be expressed only at 4 weeks after embolization. Cells within aneurysm cavity were TUNEL positive at 4 weeks only. Expression of tumor necrosis‐&#945; (TNF‐&#945;) was high in coiled aneurysm when compared with controls. There was no significant difference in the expression of Fas‐ligand among groups. Decreased expression of antiapoptotic protein, Bcl‐2, and increased expression of proapoptotic proteins, Bad, Bax and Bid, were observed in coiled aneurysms at both time points. Conclusion: Activation apoptosis in aneurysms after embolization with platinum coils is mediated by both TNF‐&#945; mediated‐extrinsic and Bcl‐2 mediated‐intrinsic pathway.