Impact of Thrombus Length on Outcomes After Intra-Arterial Aspiration Thrombectomy in the THERAPY Trial.

BACKGROUND AND PURPOSE: Increasing thrombus length (TL) impedes recanalization after intravenous (IV) thrombolysis. We sought to determine whether the clinical benefit of aspiration thrombectomy relative to IV r-tPA (recombinant tissue-type plasminogen activator) may be greater at longer TL. METHODS: THERAPY was a randomized trial of aspiration thrombectomy plus IV r-tPA versus IV r-tPA alone in large-vessel stroke patients with prospective TL measurement ≥8 mm. In this post hoc study, we evaluated the association of TL with trial end points and potential endovascular treatment effect, using univariate, multivariable, and multiplicative interaction analyses. RESULTS: TL data were available for all 108 patients (28% internal carotid artery, 62% M1, and 10% M2). Median TL was 14.0 mm (interquartile range, 9.7-19.5 mm). Longer TL was associated with worse outcome (90-day modified Rankin Scale score: odds ratio, 1.24 per 5-mm TL increment; 95% confidence interval, 1.04-1.52; P=0.02), even after adjusting for key outcome predictors (adjusted P=0.004). Longer TL was also associated with more serious adverse events (adjusted P=0.01), more symptomatic hemorrhages (adjusted P=0.03), and increased mortality (adjusted P=0.01). No significant relationship was observed between TL and angiographic reperfusion (modified thrombolysis in cerebral ischemia 2b-3), but greater TL was associated with longer endovascular procedural times (ρ=0.36; P=0.045). Increasing TL was associated with greater aspiration thrombectomy treatment effect (interaction term P=0.03). This might be related to a potentially stronger adverse effect of increasing TL on 90-day modified Rankin Scale for patients treated with IV r-tPA (ρ=0.39; P=0.01) compared with intra-arterial therapy (ρ=0.20; P=0.165). CONCLUSIONS: Ischemic stroke patients with longer symptomatic thrombi have worse 90-day clinical outcomes but may have a greater relative benefit of aspiration thrombectomy over IV r-tPA alone. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01429350.

Safety and performance of the Penumbra Liberty stent system in a rabbit aneurysm model.

BACKGROUND: Endovascular treatment of wide necked and large/giant intracranial aneurysms is challenging. The goal of this study was to evaluate the Liberty stent system in the rabbit elastase aneurysm model for 30, 90, and 180 days. METHODS: The Altes elastase model was used to create aneurysms in the right common carotid artery in New Zealand White rabbits. Safety was assessed by angiographic and histopathological data from treated wide necked aneurysms, treated subclavian arteries, and related vasculature immediately post-treatment and at scheduled end points. RESULTS: In this study, stenting of wide necked aneurysms demonstrated excellent results in all 35 animals. The Liberty could be tracked to the final position across an aneurysm neck precisely, without changing microcatheter position. After device deployment, no significant changes in vessel contour and no stent migration were observed. Coil mass was well supported in all aneurysms and high packing densities were achieved. In addition, follow-up angiograms showed stable coil masses and persistent occlusion in all animals, without any recanalization of the neck or aneurysmal sac. Furthermore, there was no evidence of coil compaction or protrusion of coil loop through the stent struts. None of the immediate post-coiling angiograms revealed evidence of vasospasm, dissection, or in-stent thrombosis. DISCUSSION: This animal study demonstrated promising results with the novel Liberty stent system. The Liberty showed consistent precise positioning and accurate deployment. The stent revealed good compatibility with embolic coiling procedures, while morbidity and mortality were negligible. In addition, persistent occlusion of aneurysms without recanalization or in-stent stenosis was observed at the 180 day follow-up.

Impact of pretreatment noncontrast CT Alberta Stroke Program Early CT Score on clinical outcome after intra-arterial stroke therapy.

BACKGROUND AND PURPOSE: The efficacy of intra-arterial treatment remains uncertain. Because most centers performing IAT use noncontrast CT (NCCT) imaging, it is critical to understand the impact of NCCT findings on treatment outcomes. This study aimed to compare functional independence and safety among patients undergoing intra-arterial treatment stratified by the extent of ischemic change on pretreatment NCCT. METHODS: The study cohort was derived from multicenter trials of the Penumbra System. Inclusion criteria were anterior circulation proximal occlusion, evaluable pretreatment NCCT, and known time to reperfusion. Ischemic change was quantified using the Alberta Stroke Program Early CT Score (ASPECTS) and stratified into 3 prespecified groups for comparison: 0 to 4 (most ischemic change) versus 5 to 7 versus 8 to 10 (least ischemic change). RESULTS: A total of 249 patients were analyzed: 40 with ASPECTS 0 to 4, 83 with ASPECTS 5 to 7, and 126 with ASPECTS 8 to 10. For ASPECTS 0 to 4, 5 to 7, and 8 to 10, respectively, good outcome (modified Rankin Scale score, 0-2) rates were 5%, 38.6%, and 46% (P<0.0001), and mortality rates were 55%, 28.9%, and 19% (P=0.0001). The only significant pairwise differences were between ASPECTS 0 to 4 and other groups. Symptomatic hemorrhage was more common with lower ASPECTS (P=0.02). Shorter time to reperfusion was significantly associated with better outcomes among patients with ASPECTS 8 to 10 (P=0.01). A similar relationship was seen for ASPECTS 5 to 7 but was not statistically significant. No such relationship was seen for ASPECTS 0 to 4. CONCLUSIONS: NCCT seems useful for excluding patients with the greatest burden of ischemic damage from futile intra-arterial treatment, which is unlikely to result in patient functional independence and increases the risk of hemorrhage.

Clot length distribution and predictors in anterior circulation stroke: implications for intra-arterial therapy.

BACKGROUND AND PURPOSE: Thin-section noncontrast computed tomography images can be used to measure hyperdense clot length in acute ischemic stroke. Clots≥8 mm have a very low probability of intravenous tissue-type plasminogen activator recanalization and hence may benefit from a bridging intra-arterial approach. To understand the prevalence of such clots, we sought to determine the distribution and predictors of clot lengths in consecutive anterior circulation proximal artery occlusions. METHODS: Of 623 consecutive patients with acute ischemic stroke, 53 met inclusion criteria: presentation<8 hours from onset; intracranial internal carotid artery-terminus or proximal-middle cerebral artery occlusion; admission thin-slice noncontrast computed tomography (≤2.5 mm); and no intravenous tissue-type plasminogen activator pretreatment. For each patient, hyperdense clot length was measured and recorded along with additional relevant imaging and clinical data. RESULTS: Mean age was 70 years, and mean time to computed tomography was 213 minutes. Median baseline National Institutes of Health Stroke Scale was 16.5. Occlusions were located in the internal carotid artery-terminus (34% [18 of 53]), middle cerebral artery M1 (49% [26 of 53]) and M2 segments (17% [9 of 53]). Hyperdense thrombus was visible in 96%, with mean and median clot lengths (mm) of 18.5 (±14.2) and 16.1 (7.6-25.2), respectively. Occlusion location was the strongest predictor of clot length (multivariate, P=0.02). Clot length was ≥8 mm in 94%, 73%, and 22% of internal carotid artery-terminus, M1, and M2 occlusions, respectively. CONCLUSIONS: The majority of anterior circulation proximal occlusions are ≥8 mm long, helping to explain the low published rates of intravenous tissue-type plasminogen activator recanalization. Internal carotid artery-terminus occlusion is an excellent marker for clot length≥8 mm; vessel-imaging status alone may be sufficient. Thin-section noncontrast computed tomography seems useful for patients with middle cerebral artery occlusion because of the wide variability of clot lengths.

A novel, self-expanding, nitinol stent in medically refractory intracranial atherosclerotic stenoses: the Wingspan study.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the safety and performance of the Wingspan stent system and Gateway percutaneous transluminal angioplasty balloon catheter in the treatment of high-grade, intracranial atherosclerotic lesions in patients who had failed medical therapy. METHODS: In this prospective, multicenter, single-arm study, medically refractory patients with a modified Rankin score < or =3 and recurrent symptoms attributable to angiographically demonstrated intracranial stenosis > or =50% in a vessel 2.5 to 4.5 mm in diameter were enrolled. Intracranial lesions were predilated with an undersized Gateway balloon catheter to 80% of the native vessel diameter, followed by deployment of the self-expanding Wingspan stent to facilitate further remodeling of the atherosclerotic plaque and to maintain vessel patency. Neurologic examinations and angiograms were performed at 6 months after the procedure. RESULTS: Among the 45 patients enrolled, the degree of stenosis was reduced from a baseline of 74.9+/-9.8% to 31.9+/-13.6% after stenting and 28+/-23.2% at the 6-month follow-up. The 30-day composite ipsilateral stroke/death rate was 4.5% (2/44); at the 6-month follow-up, the ipsilateral stroke/death rate was 7.0%, the rate for all strokes was 9.7%, and all-cause mortality was 2.3%. Physician-reported follow-up in 43 patients (average of 13 months) conducted outside the study protocol (not adjudicated by the clinical event committee) reported 1 additional ipsilateral stroke. CONCLUSIONS: In medically refractory patients with high-grade intracranial atherosclerotic stenoses, a new treatment paradigm involving predilation with an undersized Gateway percutaneous transluminal angioplasty balloon catheter and placement of a self-expanding Wingspan stent system appears to be safe, may facilitate remodeling, and may contribute to favorable angiographic outcomes.