Predictors of Good Outcomes in Patients with Failed Endovascular Thrombectomy

Based on five randomized clinical trials, endovascular mechanical thrombectomy (EVT) is recommended as a standard treatment for anterior circulation large vessel occlusion (AC-LVO) (1, 2). In addition, the diffusion-weighted imaging or CT perfusion assessment with clinical mismatch in the triage of wake up and late presenting stroke undergoing neurointervention with Trevo (DAWN) and Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke-3 (DEFUSE-3) trials demonstrated the benefit of EVT in late-presenting AC-LVO through strict patient selection criteria (3, 4).

The selection criteria in many clinical trials for EVT were developed to identify factors related to patient outcomes after EVT. Lower initial National Institutes of Health Stroke Scale (NIHSS), shorter procedure time, smaller early ischemic change on non-contrast computed tomography (CT), lower serum glucose, good collateral status, and recanalization success were predictive factors for good outcome after EVT (5, 6, 7, 8, 9). Among them, successful recanalization (defined as modified thrombolysis in cerebral infarction scale [mTICI] grade 2b or 3) was the most important factor for patient outcomes after EVT (9).

In an era of modern EVT, approximately 20% of patients do not achieve successful recanalization (3, 4). However, to our knowledge, the prognosis and factors that affect clinical outcomes in patients without successful recanalization despite modern EVT are not well known. In this study, we intended to evaluate the prognostic factors in non-recanalized AC-LVO patients despite EVT.

Altogether, 805 patients had undergone EVT for acute ischemic stroke with a stent retriever, penumbra, or both between September 2010 and December 2015. Among them, 765 patients (95.0%) had mRS available at 3 months, of whom 690 (90.2%) fulfilled the enrolment criteria. Of these 690 patients, 136 (19.7%) had recanalization failure despite EVT and were enrolled in this study (Fig. 1).

Fig. 1
Flow chart of patients' inclusion.
CTA = computed tomography angiography, EVT = endovascular thrombectomy, ICA = internal carotid artery, mRS = modified Rankin Scale, mTICI = modified thrombolysis in cerebral ischemia, NIHSS = National Institutes of Health Stroke Scale

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Thirty-five (25.7%) of the non-recanalized patients had good outcome. The good outcome group was younger, had a lower incidence of hypertension, lower distal ICA involvement, and lower initial NIHSS and good collateral status (Table 1).

Table 1
Predictors for Good Outcomes in Patients with Recanlization Failure (n = 136)

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In univariate analysis, the initial NIHSS, good collateral status, and beyond distal ICA involvement were associated with good outcome. In addition, the distal ICA involvement was negatively associated with good outcome (Table 1). After adjusting for potentially associated factors in univariate analysis (p < 0.20), including age, hypertension, initial NIHSS, mTICI 2a recanalization, distal ICA involvement, beyond distal ICA involvement and good collateral status, the initial NIHSS (OR, 0.760; 95% CI, 0.638–0.905, p = 0.002), good collateral status (OR, 14.130; 95% CI, 2.264–88.212, p = 0.005) and mTICI 2a recanalization (OR, 5.636; 95% CI, 1.216–26.119, p = 0.027) remained independent factors with good outcome in non-recanalized patients (Table 1). The model was fairly calibrated (p = 0.599 by the Hosmer-Lemeshow test) with reasonable discrimination (C statistics = 0.915).

The patients with mTICI 2a recanalization and good collateral had a relatively higher probability of good outcome in the recanalization failure group. This study is, to our knowledge, the first to identify prognostic factors associated with clinical outcomes in patients with recanalization failure, despite modern EVT.

Recanalization success is one of the most important factors affecting clinical outcome in patients who receive EVT (9). Conventionally, recanalization is defined as mTICI 2b (contrast agent filling more than 50% of the affected artery) or 3 (complete filling). The mTICI 2a recanalization is defined as the contrast agent filling less than 50% of the affected vascular territory. The mTICI 0 and 1 are defined as no or minimal recanalization (perfusion past the initial obstruction but limited distal branch filling with little or no distal perfusion), respectively. For example, if a patient had an occlusion of the right MCA M1 segment, recanalization of either the superior or the inferior M2 division alone might be graded as mTICI 2a. Intuitively, mTICI 2a reperfusion can benefit patients more than mTICI 0 or 1.

The collateral status has been suggested as a strong predictor for both recanalization success and functional outcome (13, 14, 15, 16, 17, 18, 19). Retrograde collateral filling may help thrombolytic agents to access the distal aspects of a clot (20). Moreover, the degree of ischemic vascular injury after vessel occlusion can be minimized by the collateral supply. Thus, the response to intravenous tissue plasminogen activator and EVT could be improved in patients with good collaterals (12). In addition, the time to reperfusion to improve the likelihood of good outcome can be adjusted for the collateral status (10), which was an important background factor in the late window trials, such as DAWN and DEFUSE-3 (3, 4).

In our study, we also confirmed that good collateral status was significantly associated with good outcomes even in the case of a failed EVT. In addition, mTICI 2a recanalization provided benefit for the outcome of patients with failed EVT. According to previous reports, the presence of proximal artery occlusion without absence of early recanalization led to neurological deterioration through hemodynamic compromise (21). This result indicates that good collateral status does not completely protect brain tissue; rather delays ischemic injury in various ways. Alternatively, timely recanalization in addition to good collateral status is essential for achieving a good outcome. Similarly, mTICI 2a recanalization may have a more positive effect on clinical outcome in patients with good collaterals; however, non-recanalization in all poor collateral patients resulted in poor outcome regardless of the mTICI grade (0–1 vs. 2a).

Previous studies identified younger age, lower NIHSS, good collateral, lower serum glucose, lower ASPECTS, and successful recanalization as independent predictors for good outcome (5, 6, 7, 8, 9). In our study, age and baseline ASPECTS were not associated with good outcomes in the non-recanalization group. Good outcome is less common in patients > 80 years (22). In this study, most patients were younger than 80 years, and age did not differ significantly between the groups. In addition, baseline ASPECTS was similar in the two groups in this study. Thus, ASPECTS did not affect patient outcome. Lower NIHSS was an independent predictive factor for good outcome after successful recanalization (23). As the collateral status was categorized as good or poor in this study, it might not reflect a detailed status. Initial neurological severity may reflect a more precise collateral status even among the good collateral group and, thus, remain independently associated with the clinical outcome.

Finally, the use of tissue plasminogen activator (tPA) was not associated with good outcome in this study. Currently, the question whether EVT without prior tPA is better or worse than EVT with tPA has been of concern. (24, 25) The benefits of tPA before EVT is that tPA can lead to spontaneous successful recanalization before EVT, especially in the case of near-occlusion or short thrombi and significantly lowers the number of passes required to achieve successful recanalization (26). Alternatively, tPA can help achieve successful recanalization, which may lead to a good outcome. In our study, we only included the non-recanalized AC-LVO patients despite EVT. Thus, the effect of tPA may be limited.

This study had some strengths and limitations. Many attributable reasons regarding failure to achieve successful recanalization, defined as mTICI 2b–3, have been suggested (27). We did not collect the information regarding reasons of failure of EVT and the point when EVT attempts were discontinued, as the EVT strategy of each participating hospital was different. Nevertheless, the primary focus of this study was to determine the predictors for a good outcome despite a failed EVT. The collateral status was assessed with single-phase CTA, as it is the most widely used modality at the participating centers (93.5% of enrolled patients). Due to delayed circulation time after beginning the CTA scan, contrast agent filling of cerebral arteries through collaterals on single-phase CT is insufficient. Thus, using single-phase CTA can result in good collaterals misclassified as poor collaterals. However, we only included patients with clearly visible vessel markings in the contralateral normal hemisphere. In addition, we only included the first phase image for patients who underwent multiphase CTA to increase inter-rater agreement. Finally, mTICI 2a recanalization and good collateral illustrated a wide range of confidence interval due to our relatively small sample size. Thus, future studies with a large sample size are required. Therefore, interrater agreement was excellent for the discrimination of poor and good collateral status and for of mTICI 0–1 and mTICI 2a. Despite the retrospective nature of our study, our study population represents at least 10% of all patients who received EVT in Korea during the study period, based on nationwide data from the Health Insurance Review and Assessment Service. Therefore, the results of this study reflect real-world practice in Korea.

In conclusion, lower initial NIHSS, good collateral, and mTICI 2a recanalization were independent predictors of good outcome in patients with recanalization failure despite EVT. This result suggests that mTICI 2a recanalization would benefit patients with good collateral, even if recanalization were not successful despite EVT.