Impact of Modified TICI 3 versus Modified TICI 2b Reperfusion Score to Predict Good Outcome following Endovascular Therapy

Inclusion Criteria

In this retrospective study, data were extracted from a bicentric prospective clinical registry (EFFECTS registry, Endovascular Treatment at Foch Hospital–Rothschild Foundation for Ischemic Stroke) of consecutive patients treated by mechanical thrombectomy for acute cerebral infarct between January 2012 and November 2015. The local ethics committees approved the use of patient data for this retrospective analysis.

All patients referred for endovascular treatment of acute intracranial large-vessel occlusion involving the anterior circulation, with the exception of tandem and multifocal occlusions, were potentially included. Inclusion criteria were the following: 1) middle cerebral artery M1 or M2 segment and/or intracranial internal carotid artery occlusion; 2) intracranial artery occlusion and acute stroke confirmed on cerebral MRA and DWI, respectively; and 3) achievement of mTICI 2b or mTICI 3 reperfusion status after endovascular treatment by mechanical thrombectomy. Exclusion criteria were the following: 1) patients without baseline functional independence (modified Rankin Scale score of >2), and 2) patients with tandem occlusions, with >1 cerebral territory involved or a large ischemic score (DWI-ASPECTS < 6).

Patient Characteristics

Patient demographics, vascular risk factors, imaging findings, vital signs before treatment, severity of ischemic stroke, and clinical outcomes were collected prospectively with a structured questionnaire. Data on age, sex, cardiovascular risk factors (hypertension, dyslipidemia, diabetes, and smoking habits), time of symptom onset, National Institutes of Health Stroke Scale score at baseline and day 1, use of IV thrombolytics, and time of IV thrombolysis were collected. The Alberta Stroke Program Early CT Score on diffusion-weighted MR imaging was calculated by a neuroradiologist blinded to the results of the endovascular procedure. For each patient, the final mTICI score was retrospectively assessed by a neurointerventionalist (C.D.) blinded to both the first reader's scoring and the clinical outcome. A consensus was reached with an additional reader (M.P.) for cases with discrepant judgments. After an in-hospital work-up, stroke etiology was defined, according to the Trial of ORG 10172 in Acute Stroke Treatment classification.⁸

Endovascular Procedure

All patients were treated in a dedicated neuroangiography suite under general anesthesia or conscious sedation, after evaluation by a dedicated anesthesiology team. The thrombectomy device was chosen at the interventionalist's discretion, by using a stent retriever or A Direct Aspiration First-Pass Technique (ADAPT) in the first instance. Arterial occlusion site, time from symptom onset to groin puncture, procedure time, and time to reperfusion were recorded. Reperfusion results were reported by using the mTICI score and were defined as ranging from no reperfusion (mTICI 0) to complete reperfusion (mTICI 3), including partial reperfusion (mTICI 2). Partial perfusion occurs when the iodine contrast medium passes beyond the obstruction, opacifying the distal arterial bed but with a rate of entry of contrast material and/or its rate of clearance from the vascular bed slower than that in comparable areas not perfused by the previously occluded vessel. The contralateral cerebral angiography, often available for T-carotid occlusions, was used for comparison. In other cases, the arterial bed proximal to the occlusion could be used for comparisons. mTICI 2 was further divided into 2a and 2b as less than and greater than 50%, respectively.⁹ This definition is different from the original TICI score in which 2a was defined as less than two-thirds perfusion of the distal territory, and 2b, as greater than two-thirds perfusion.¹⁰ Collateral arterial supply was assessed by using the capillary index score,¹¹ and patients were dichotomized into favorable and unfavorable collateral flow groups (capillary index score 2 or 3 and capillary index score 0–1, respectively). Periprocedural complications (embolization in a new territory, defined as an angiographic occlusion in a previously unaffected vascular territory observed on the angiogram after clot removal; arterial dissection or perforation; vasospasm; and subarachnoid hemorrhage) were also noted.

A Direct Aspiration First-Pass Technique Group

Patients in this treatment arm received aspiration thrombectomy by ADAPT by using the 5MAX ACE Reperfusion Catheter (Penumbra, Alameda, California) as frontline therapy. The detailed technical procedure has been published previously.¹² In brief, access was achieved through the femoral artery in compliance with the standard of care. A large-bore catheter was placed distally into the internal carotid artery to provide access for the 5MAX ACE aspiration catheter. Adhering to the instructions for use, we then performed aspiration by using the Penumbra Aspiration Pump (Penumbra, Alameda, California) in all cases. Angiography was performed following recovery to evaluate the flow rate. Steps were repeated if necessary until successful reperfusion to mTICI 2b–3 was achieved. The interventional neuroradiologist could, in case of reperfusion failure (mTICI < 2b) with ADAPT, use another thrombectomy device of the operator's choice (rescue therapy).

Stent-Retriever Group

Procedures were performed by using the Solitaire FR (Covidien, Irvine, California) or the Trevo device (Stryker, Kalamazoo, Michigan) via the femoral artery approach. Following the instructions for use of the stent retriever, we positioned a balloon catheter within the internal carotid artery to allow flow arrest during thrombus retrieval. The stent retriever was delivered through a microcatheter and deployed inside the thrombus. A control angiogram was performed to determine the immediate reperfusion status, and the device was left deployed for a minimum of 3 minutes. Subsequently, the device and microcatheter were slowly retrieved. A control angiogram was obtained to assess recanalization and reperfusion.^13,14 This sequence was repeated until mTICI 2b or 3 flow (defined as successful reperfusion) was established. The interventional neuroradiologist could, in the case of reperfusion failure (mTICI < 2b) with the stent retriever, use another thrombectomy device of the operator's choice (rescue therapy).

Adjunctive Therapies

Use of complementary mechanical (intracranial angioplasty or stent placement) and/or pharmacologic treatment was recorded. Complementary pharmacologic treatments used were intra-arterial fibrinolysis (alteplase) or intravenous administration of abciximab (Reopro).

Follow-Up and Outcome

All patients underwent cross-sectional imaging (CT or MR imaging) within 18–24 hours after the procedure. Intracranial hemorrhage (ICH) was classified according to the European Cooperative Acute Stroke Study (ECASS) criteria.¹⁵ Patients were evaluated 24 hours after the procedure by using the NIHSS, and “symptomatic intracranial hemorrhage” was defined as any intracerebral hemorrhage with an increase of at least 4 NIHSS points within 24 hours, or resulting in death. The mRS at 90 days was assessed by trained research nurses unaware of the study group assignments during face-to-face interviews or via telephone conversations with the patients, their relatives, or their general practitioners.

The primary study outcome was the achievement of an mRS score of 0–2 at 3 months (favorable outcome). Secondary outcomes included excellent outcome (defined as an mRS score of 0–1), any ICH, all-cause mortality at 90 days, and procedural complications. Furthermore, attention was given to the type of endovascular procedure performed for all patients.

Statistical Analysis

Quantitative variables are expressed as means ± SD or medians (interquartile range [IQR]), and categoric variables are expressed as numbers (percentages). Normality of distributions was assessed by using histograms and the Shapiro-Wilk test. Bivariate comparisons between complete and mTICI 2b reperfusion groups were made by using the χ² test or Fisher exact test for categoric variables, the Cochran-Armitage Trend test for ordinal variables, and the Student t test or Mann-Whitney U test for quantitative variables as appropriate. We assessed the heterogeneity in the relationship between successful reperfusion status and each outcome (excellent outcome, favorable outcome, 90-day mortality, and any ICH) across the 2 centers by using the Breslow-Day test. Comparisons in outcomes between the 2 successful reperfusion groups were further adjusted for the center and prespecified confounders regarding prior evidence of an association with clinical outcome (namely age, diabetes, admission NIHSS score, site of occlusion, collateral flow, etiology, previous IV thrombolysis, and onset to reperfusion time) by using logistic regression models.⁷ An additional adjustment for ICH occurrence was performed for comparison in functional outcomes (excellent and favorable). To avoid case deletion in multivariable analyses due to missing data on the collateral favorable covariate (missing in 14 patients), we imputed missing data under a missing-at-random assumption by using a regression-switching approach (chained equation with m = 10 imputations obtained by using the R statistical software, Version 3.03; http://www.r-project.org/).^16,17 Imputation procedures were performed by using all variables listed in Table 1 and each study outcome. Multiple imputed datasets were combined by using the Rubin rules.¹⁸ Unadjusted and adjusted odds ratios for reaching each outcome were calculated by using mTICI 2b as the reference group. Statistical testing was performed at the 2-tailed α level of .05. Data were analyzed by using SAS software, Version 9.3 (SAS Institute, Cary, North Carolina).