No-Reflow Post-Recanalization in Acute Ischemic Stroke: Mechanisms, Measurements, and Molecular Markers

Sperring, Colin P.; Savage, William M.; Argenziano, Michael G.; Leifer, Valia P.; Alexander, Julia; Echlov, Nicolas; Spinazzi, Eleonora F.; Connolly, E. Sander

doi:10.1161/strokeaha.123.044240

Cited by 14 publications

(1 citation statement)

References 72 publications

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“…5 Moreover, even when tissue is visibly reperfused at the macroscopic level, microcirculatory nonreperfusion (the 'no-reflow' phenomenon) can prevent nutritive reperfusion. 6 Intra-arterial infusion of adjunctive thrombolytic agent after successful reperfusion with EVT has the potential to further improve outcome by lysing persisting visible thrombi in distal arteries…”

Section: Introductionmentioning

confidence: 99%

Intra-arterial tenecteplase following endovascular therapy in patients with acute posterior circulation arterial occlusion: study protocol and rationale

Tao,

Li,

Sun

et al. 2023

J NeuroIntervent Surg

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BackgroundRecently, a randomized controlled trial showed a beneficial effect of intra-arterial thrombolysis following successful endovascular thrombectomy (EVT) in patients with acute ischemic stroke due to large vessel occlusion in the anterior circulation. Due to differences in response to thrombolytics in occlusion of the posterior circulation, the purpose of ATTENTION IA is to explore the adjunct benefit of intra-arterial thrombolysis after successful recanalization in patients presenting with large and medium vessel occlusion of the posterior circulation.MethodsATTENTION-IA is an investigator-initiated, multicenter, prospective, randomized clinical trial with open-label treatment and blinded endpoint assessment (PROBE). After achieving successful recanalization (expanded Thrombolysis In Cerebral Infarction (eTICI) 2b-3) of an occlusion of the vertebral, basilar, or posterior cerebral artery, patients will be randomized 1:1 to receive intra-arterial tenecteplase or standard of care. The primary effect parameter is a modified Rankin Score of 0–1 at day 90.ResultsThe trial recently completed enrollment, and data collection/verification is ongoing. The final results will be made available on completion of enrollment and follow-up.ConclusionsATTENTION-IA will provide definitive evidence for the efficacy and safety of adjunct intra-arterial tenecteplase after successful EVT in patients with an acute posterior circulation arterial occlusion stroke presenting within 24 hours of symptom onset.Trial registrationClinicalTrials.govNCT05684172.

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Section: Introductionmentioning

confidence: 99%

Intra-arterial tenecteplase following endovascular therapy in patients with acute posterior circulation arterial occlusion: study protocol and rationale

Tao,

Li,

Sun

et al. 2023

J NeuroIntervent Surg

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CHA₂DS₂‐VASc score and prior oral anticoagulant use on endovascular treatment for acute ischemic stroke

Imaoka,

Ren,

Ogata

et al. 2024

Ann Clin Transl Neurol

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ObjectiveWe evaluated the effect of CHA2DS2‐VASc score and prior use of oral anticoagulants (OACs) on endovascular treatment (EVT) in patients with acute ischemic stroke and atrial fibrillation (AF).MethodsPatients with AF who received EVT in 353 centers in Japan (2018–2020) were included. The outcomes were symptomatic intracerebral hemorrhage (sICH), in‐hospital mortality, functional independence, and successful and complete reperfusion. The effects of CHA2DS2‐VASc score, its components, and prior use of OACs were assessed via a multiple logistic regression model.ResultsOf the 6984 patients, 780 (11.2%) used warfarin and 1168 (16.7%) used direct oral anticoagulants (DOACs) before EVT. Based on the CHA2DS2‐VASc score, 6046 (86.6%) presented a high risk (≥2 for males and ≥3 for females) while 938 (13.4%) had intermediate to low risks. Higher CHA2DS2‐VASc scores were associated with increased sICH, in‐hospital mortality, and decreased functional independence, regardless of prior OACs. For patients with a high‐risk category, prior DOACs increased the odds of successful and complete reperfusion (adjusted odds ratio [95% confidence interval (CI)], 1.27 [1.00–1.61] and 1.30 [1.10–1.53]). For those with integrated intermediate to low risks, neither prior warfarin nor DOAC affected the outcomes. Regardless of total CHA2DS2‐VASc scores, patients with congestive heart failure or left ventricular dysfunction, hypertension, age >75 years, or female benefited similarly from prior DOAC use.InterpretationPrior DOAC use for patients with high‐ and selected intermediate‐risk CHA2DS2‐VASc scores increased prevalence of successful and complete reperfusion. These findings may provide supplemental evidence to introduce preventive DOAC for patients with AF.

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Comparison of Perfusion Imaging Definitions of the No‐Reflow Phenomenon after Thrombectomy—What Is the Best Perfusion Imaging Definition?

Mutimer,

Mujanovic,

Kaesmacher

et al. 2024

Annals of Neurology

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The no‐reflow phenomenon is a potential contributor to poor outcome despite successful thrombectomy. There are multiple proposed imaging‐based definitions of no‐reflow leading to wide variations in reported prevalence. We investigated the agreement between existing imaging definitions and compared the characteristics and outcomes of patients identified as having no‐reflow.MethodsWe performed an external validation of 4 existing published definitions of no‐reflow in thrombectomy patients with extended Thrombolysis in Cerebral Infarction scale 2c to 3 (eTICI2c‐3) angiographic reperfusion who underwent 24‐hour perfusion imaging from 2 international randomized controlled trials (EXTEND‐IA TNK part‐1 and 2) and a multicenter prospective observational study. Receiver‐operating‐characteristic and Bayesian‐information‐criterion (BIC) analyses were performed with the outcome variable being dependent‐or‐dead at 90‐days (modified Rankin Score [mRS] ≥3).ResultsOf 131 patients analyzed, the prevalence of no‐reflow significantly varied between definitions (0.8–22.1%; p < 0.001). There was poor agreement between definitions (kappa 5/6 comparisons <0.212). Among patients with no‐reflow according to at least 1 definition, there were significant differences between definitions in the intralesional interside differences in cerebral blood flow (CBF) (p = 0.006), cerebral blood volume (CBV) (p < 0.001), and mean‐transit‐time (MTT) (p = 0.005). No‐reflow defined by 3 definitions was associated with mRS ≥3 at 90 days. The definition of >15% CBV or CBF asymmetry was the only definition that improved model fit on BIC analysis (ΔBIC = −8.105) and demonstrated an association between no‐reflow and clinical outcome among patients with eTICI3 reperfusion.ConclusionsExisting imaging definitions of no‐reflow varied significantly in prevalence and post‐treatment perfusion imaging profile, potentially explaining the variable prevalence of no‐reflow reported in literature. The definition of >15% CBV or CBF asymmetry best discriminated for functional outcome at 90 days, including patients with eTICI3 reperfusion. ANN NEUROL 2024;96:1104–1114

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No-Reflow Post-Recanalization in Acute Ischemic Stroke: Mechanisms, Measurements, and Molecular Markers

Cited by 14 publications

References 72 publications

Intra-arterial tenecteplase following endovascular therapy in patients with acute posterior circulation arterial occlusion: study protocol and rationale

Intra-arterial tenecteplase following endovascular therapy in patients with acute posterior circulation arterial occlusion: study protocol and rationale

CHA₂DS₂‐VASc score and prior oral anticoagulant use on endovascular treatment for acute ischemic stroke

Comparison of Perfusion Imaging Definitions of the No‐Reflow Phenomenon after Thrombectomy—What Is the Best Perfusion Imaging Definition?

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No-Reflow Post-Recanalization in Acute Ischemic Stroke: Mechanisms, Measurements, and Molecular Markers

Cited by 14 publications

References 72 publications

Intra-arterial tenecteplase following endovascular therapy in patients with acute posterior circulation arterial occlusion: study protocol and rationale

Intra-arterial tenecteplase following endovascular therapy in patients with acute posterior circulation arterial occlusion: study protocol and rationale

CHA2DS2‐VASc score and prior oral anticoagulant use on endovascular treatment for acute ischemic stroke

Comparison of Perfusion Imaging Definitions of the No‐Reflow Phenomenon after Thrombectomy—What Is the Best Perfusion Imaging Definition?

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CHA₂DS₂‐VASc score and prior oral anticoagulant use on endovascular treatment for acute ischemic stroke