Occult Anterograde Flow Is an Under-Recognized but Crucial Predictor of Early Recanalization With Intravenous Tissue-Type Plasminogen Activator

Ahn, Seong Hwan; d’Esterre, Christopher D; Qazi, Emmad; Najm, Mohammed; Rubiera, Marta; Fainardi, Enrico; Hill, Michael D.; Goyal, Mayank; Demchuk, Andrew M.; Lee, Ting Y.; Menon, Bijoy K

doi:10.1161/strokeaha.114.008648

Cited by 40 publications

(28 citation statements)

References 18 publications

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“…Our findings on the increased rate of intravenous r-tPAinduced recanalization with increasing perviousness is consistent with both preclinical 6 and clinical studies. [13][14][15] In a previous study using lysis modeling of fibrin thrombi with various permeability, it was demonstrated that lysis would require hundreds of minutes in impermeable thrombi. 6 Other studies demonstrated an association between success of recanalization after intravenous r-tPA and qualitative assessment of flow passing through a thrombus for both ischemic stroke and coronary occlusion.…”

Section: Discussionmentioning

confidence: 99%

“…6 Other studies demonstrated an association between success of recanalization after intravenous r-tPA and qualitative assessment of flow passing through a thrombus for both ischemic stroke and coronary occlusion. [13][14][15] Because perviousness increased the odds of recanalization, and recanalization is associated with improved functional outcome, it is not surprising that there is a direct relation between perviousness and favorable functional outcome in the intravenous r-tPA group. However, this association was still significant after adjusting for recanalization in a multivariate model.…”

Section: Discussionmentioning

confidence: 99%

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Permeable Thrombi Are Associated With Higher Intravenous Recombinant Tissue-Type Plasminogen Activator Treatment Success in Patients With Acute Ischemic Stroke

Santos¹,

Dankbaar²,

Treurniet³

et al. 2016

Stroke

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Early complete recanalization of an occluded artery is a strong predictor of favorable functional outcome in patients with acute ischemic stroke.1 To increase the chance of favorable outcome, guidelines recommend the use of intravenous thrombolysis with recombinant tissue-type plasminogen activator (r-tPA) in eligible patients.2 Because intravenous r-tPA treatment results in a relatively low rate of recanalization, 3 it might be useful to estimate the likelihood of failure or success of intravenous r-tPA before treatment initialization.Preclinical studies have shown that thrombus permeability influences r-tPA efficacy. Permeability reflects the ability of soluble molecules to move within the gaps between adjacent platelets, fibrin filaments, and red blood cells.4,5 A high permeability might result in more effective activation of recombinant tissue-type plasminogen because of an improved surface contact area and might, therefore, increase the dissolution of the fibrin filaments and consequently the thrombus.6 These preclinical findings have not yet been studied in a clinical setting. We recently proposed a method to assess thrombus Background and Purpose-Preclinical studies showed that thrombus permeability improves recombinant tissue-type plasminogen activator (r-tPA) efficacy. We hypothesize that thrombus permeability estimated from radiological imaging is associated with improved recanalization after treatment with intravenously administered r-tPA (r-tPA) and with better functional outcome. Methods-We assessed thrombus attenuation increase (TAI) in patients from the Dutch Acute Stroke Study with an occlusion of an intracranial artery on computed tomographic angiography. Patients were included within 9 hours after the stroke onset. After dichotomization of TAI as pervious or impervious, logistic regressions analyses were performed to estimate associations of intravenous r-tPA therapy with complete recanalization and with favorable functional outcome (modified Rankin Scale score of ≤2). Results-Three hundred eight patients matched the inclusion criteria. The median TAI was 20.1 (interquartile range, 8.5-37.8) Hounsfield unit (HU). We found a significant increase in the odds of complete recanalization with increasing TAI for patients treated with intravenous r-tPA (P=0.030). One hundred thirty-one (42%) thrombi were classified as pervious with TAI of ≥23 HU. In patients with a pervious thrombus, complete recanalization was more frequent after treatment with intravenous r-tPA than after conservative treatment (odds ratio, 6.26; 95% confidence interval, 2.4-16.8; P<0.001). In patients with an impervious thrombus, the effect of intravenous r-tPA was not significant (odds ratio, 1.4; 95% confidence interval, 0.5-4.1; P=0.47). Favorable outcome was more common in patients with a pervious thrombi than without (odds ratio, 2.1; 95% confidence interval, 1.3-3.4; P=0.001). Conclusions-Thrombus perviousness, as measured on computed tomography in the acute stage of ischemic stroke, is strongly associated with recanalization...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Permeable Thrombi Are Associated With Higher Intravenous Recombinant Tissue-Type Plasminogen Activator Treatment Success in Patients With Acute Ischemic Stroke

Santos¹,

Dankbaar²,

Treurniet³

et al. 2016

Stroke

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“…Additionally, further work should explore the effects of other thrombus attributes such as thrombus density and contrast permeability on treatment outcomes. 4,[13][14][15] Advances in biomechanical characterization of thrombi will aid in optimizing endovascular devices and techniques. Until more data are available, TL measurement should not be used for treatment decision making.…”

Section: Strokementioning

confidence: 99%

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

Yoo¹,

Khatri

Mocco

et al. 2017

Stroke

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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 tissuetype 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 largevessel 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.

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“…In addition, anterograde flow across occlusion sites of cerebral arteries could be distinguished from retrograde collateral filling noninvasively by 4-D CTA [44]. In addition to this indirect contribution of CTP to imaging of occluded vessels, a recent study shows a direct parameter of CTP that can be used to evaluate the occult anterograde flow of cerebral artery occlusion in acute stroke patients [45]. Using perfusion maps that measure delay in arrival time of contrast within the intracranial artery tree (T0 maps), a positive sloped regression line of T0 values measured along artery silhouette distal to clot was observed as a marker of occult anterograde flow (permeable clot).…”

Section: Computed Tomography Perfusionmentioning

confidence: 99%

Multimodality CT based imaging to determine clot characteristics and recanalization with intravenous tPA in patients with acute ischemic stroke

et al. 2017

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Acute ischemic stroke (AIS) is a common neurovascular emergency causing significant burden to society. Currently the main focus of AIS treatment is to restore blood flow to at risk brain tissue. For the last twenty years, intravenous tissue plasminogen activator (tPA) was the only proven therapy for patients with AIS. More recently, five randomized clinical trials established the efficacy of endovascular therapy with or without intravenous tPA in selected patient populations with AIS. Not all stroke patients benefit from intravenous tPA or endovascular treatment. Nonetheless, the concept of early recanalization of occluded arteries resulting in better clinical outcomes is well established. In this focused review, we will discuss how imaging modalities such as Non-Contrast CT, CT-Angiography, and CT-Perfusion can potentially help physicians determine which patients are likely to recanalize early with intravenous tPA and therefore benefit from this therapy.

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Occult Anterograde Flow Is an Under-Recognized but Crucial Predictor of Early Recanalization With Intravenous Tissue-Type Plasminogen Activator

Cited by 40 publications

References 18 publications

Permeable Thrombi Are Associated With Higher Intravenous Recombinant Tissue-Type Plasminogen Activator Treatment Success in Patients With Acute Ischemic Stroke

Permeable Thrombi Are Associated With Higher Intravenous Recombinant Tissue-Type Plasminogen Activator Treatment Success in Patients With Acute Ischemic Stroke

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

Multimodality CT based imaging to determine clot characteristics and recanalization with intravenous tPA in patients with acute ischemic stroke

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