Microcatheter to Recanalization (Procedure Time) Predicts Outcomes in Endovascular Treatment in Patients with Acute Ischemic Stroke: When Do We Stop?

Data Collected

We recorded the presence of cardiovascular risk factors (active smoking history, hypertension, atrial fibrillation, coronary artery disease, hyperlipidemia, diabetes mellitus, prior TIA or ischemic stroke, time interval between symptom onset and endovascular intervention, and use of IV rtPA). “Procedure time” was defined by the interval between the time of positioning the microcatheter proximal to the thrombus and the time to partial or complete recanalization (based on modified Thrombolysis in Myocardial Infarction 2 or 3) or procedure termination. The times were identified by 2 authors (A.E.H. and J.T.M.) individually reviewing the angiographic images and recording the times of microcatheter placement and recanalization or completion of the procedure. We also recorded admission, 24-hour posttreatment, and discharge NIHSS scores. Outcome at the time of discharge was assessed by using the mRS, ascertained from hospital discharge summaries by the vascular neurology team and occupational, speech, and physical therapists. The principal safety end points were ICH and in-hospital mortality. Symptomatic ICH was defined as noncontrast CT–documented ICH resulting in neurologic deterioration (≥4-point worsening on an NIHSS score compared with previous clinical assessment). Favorable functional outcome at discharge was defined by an mRS score of 0–2 at discharge.

Technical Description for Endovascular Treatment

In a typical procedure, patients are brought to the neuroangiography room, and through a 6F introducer sheath in the common femoral artery, a 6F multipurpose device-guide catheter is advanced into the internal carotid artery or vertebral artery. Once the arterial occlusion is identified, a microcatheter ranging in diameter from 1.4F to 2.3F is advanced over a 0.014-inch microwire into the vessel of interest, in close proximity to the thrombus. At this given moment, arterial recanalization therapy is initiated. The techniques for endovascular treatment have been described in detail in previous publications.^{6⇓⇓⇓–10} Briefly, a combination of pharmacologic agents and/or mechanical thrombus disruption and/or retrieval is used in varying paradigms.

Patient Selection

The patient-selection criteria for endovascular treatment are described in detail in previous publications.^7,11,12 Briefly, at the University of Medicine and Dentistry of New Jersey, all patients were selected for endovascular treatment on the basis of the time interval between symptom onset and emergency department presentation and the findings of noncontrast cranial CT scan. Patients with ICH or cerebral edema, sulcal effacement, and/or focal parenchymal hypoattenuation exceeding one-third of the MCA vascular territory (in those presenting after 3 hours) were excluded. At the University of Minnesota and Hennepin County Medical Centers, the patients were selected on the basis of findings of CTA and CTP scans, in addition to the noncontrast CT. The CTP protocol follows the noncontrast cranial CT scan and is discontinued if ICH is identified. Maps obtained from data acquired by the Brilliance 64 (Philips Healthcare, Best, the Netherlands) were generated by using Vitrea software (Vital Images, Minnetonka, Minnesota), yielding the following perfusion parameters: time to peak, mean transit time, relative CBF, and relative CBV. In the case of an MCA vascular territory infarction, the patient was excluded from endovascular treatment if the infarct burden was greater than or equal to one-third of the vascular territory on qualitative analysis of the relative CBV map acquired from the CTP study.¹²

Statistical Analysis

All data were presented by using mean ± SD for continuous data and frequencies for categoric data. The frequency of baseline demographic and clinical characteristics, admission NIHSS score, time interval between symptom onset and endovascular treatment, and the interval between hospital presentation and endovascular treatment (time to microcatheter) were compared among patients with endovascularly treated acute ischemic stroke. We analyzed the effect of different time strata on discharge outcomes by using the receiver operating curve and goodness-of-fit model. We chose the smallest time interval that had an adequate number of patients resulting in a good precision estimate. We divided the patients into 2 strata based on endovascular procedure time of ≤30 and >30 minutes. The choice of 30 minutes as the cutoff for procedure time was also supported by visual analysis of scatterplots depicting recanalization response to incremental doses in 2 of our previous dose-escalating studies.^13,14 In both studies, at least half of the patients demonstrated partial or complete recanalization after administration of 4 doses of intra-arterial thrombolytics (each administered for 5 minutes) and 4 angiographic images obtained in the interim (estimated 10 minutes between each image). Therefore, there is reason to believe that 30 minutes is the earliest time to assess the procedural success.

We performed univariate analysis followed by a multivariate logistic regression model to determine the effect of procedure time on clinical outcomes at discharge. Statistical association was assessed with a t test or median 2-sample test according to normality for continuous data and the χ² test for categoric data. The rates of partial and complete angiographic recanalization, symptomatic and asymptomatic ICH, early neurologic improvement, favorable discharge outcome, and in-hospital mortality were compared between strata defined by procedure time. We performed multivariate logistic regression analysis, adjusting for admission NIHSS score, age, recanalization status, and the time interval between symptom onset and microcatheter placement, to determine the independent effect of procedure time strata and clinical outcomes. We estimated the procedure time after which favorable clinical outcome was unlikely (no greater than expected by the natural history of untreated ischemic stroke). Subsequently in a separate analysis, we compared rates of favorable outcome by using various cutoff values of total procedure time by using favorable rates observed in the placebo group in PROACT II as a reference as used in previous exploratory analysis (Mechanical Embolus Removal in Cerebral Ischemia trial).¹⁵ Our goal was to identify a procedure time cutoff after which the rate of favorable outcomes is not greater than what could be expected with a placebo infusion via a microcatheter placed within the thrombus. A P value < .05 was considered significant. All analyses were performed by using SAS statistical software (SAS, Cary, North Carolina).