Discussion

These data show that complete reperfusion (oTICI 3) in comparison with ‘almost’ complete reperfusion (oTICI 2b) is associated with substantially greater neurologic recovery and better neurologic outcome. In addition, TICI 3, and hence better neurologic recovery, was associated with significantly shorter stays in the acute hospital. These data are derived from the—to our knowledge—largest published single-center series of consecutive patients with isolated MCA occlusion successfully treated with MTE. With baseline and periprocedural data (eg, stroke severities as shown by pretreatment NIHSS scores, SORT) similar to those of the recent large MTE trials,1–5 and recanalization rates somewhat higher than in those trials that also applied the oTICI scale (79% vs the average of 68% of MR CLEAN, REVASCAT, and ESCAPE), our data are representative of current ‘state-of-the-art’ endovascular LVO-stroke treatment.

Several previous studies examined or mentioned potential differences in outcome between TICI 3 versus TICI 2b patients. In 150 successfully recanalized patients with AIS due to MCA occlusion, Yoo et al10 observed a non-significantly higher rate of good functional outcome (mRS at ∼90-days 0–2) in patients with TICI 3 according to the modified TICI scale (mTICI) proposed by Tomsick et al18 compared with patients with mTICI 2b (62% vs 46%, p=0.09). To identify predictors of poor functional outcome despite successful recanalization (‘futile’ recanalization), Linfante et al12 analyzed 234 successfully treated patients with AIS and internal carotid artery (ICA), MCA, or basilar occlusion. TICI 3 rates were higher in patients with good outcome (mRS at day 90 0–2) than in patients with poor outcome (61% vs 47%, p=0.037). After adjusting for baseline parameters and occlusion sites, however, TICI 2b vs TICI 3 (TICI scale version unspecified) was no significant predictor of outcome in their multivariate regression model. Rangaraju et al,13 in a conference paper, reported smaller infarcts and higher rates of good outcome (mRS at day 90 0–2) in TICI 3 patients, but analyzed a mixed population of 99 patients with either ICA or MCA occlusion, and did not specify the TICI scale version applied. Finally, Almekhlafi et al,14 in a study on the newly proposed TICI 2c category (see below), reported better outcomes for TICI 2c and TICI 3 than for TICI 2b patients in a sample of 110 patients with anterior circulation strokes, but did not report (or stratify according to) occlusion sites. Overall, these previous studies yielded inconsistent results that do not permit definitive conclusions owing to inhomogeneous patient samples, lack of clarity about the applied version of the TICI scale, or moderate sample sizes.

The TICI scale has many variations,19 but the most widely referred to are Higashida's original version8 and mTICI proposed by Tomsick et al,18 which draw the boundaries between TICI 2a and TICI 2b at 66% and 50% reperfused territory, respectively. Both versions show comparable interobserver agreement and provide a valid and clinically relevant assessment of ‘success’—as multiple studies reported substantial differences in outcome between TICI 2a and TICI 2b11 for either version of the scale.10 However, the TICI 2b criterion of, in particular, the mTICI scale has legitimately been criticized as covering too broad a range of—technically and clinically quite distinct—recanalization results.14 Goyal and colleagues therefore proposed an additional TICI 2c category, defined as “near complete perfusion except for slow flow in a few distal cortical vessels, or presence of small distal cortical emboli”.20 Almekhlafi et al14 subsequently reported that a combined criterion subsuming TICI 2c/3 as ‘successful’ recanalization was a more accurate predictor of favorable clinical outcome than the widely applied mTICI 2b/3 criterion. However, while these studies deal with an important issue, we found the proposed TICI 2c category difficult to apply because of the rather vague criteria: ‘near complete’, ‘slow flow’, ‘a few’, ‘distal cortical’, ‘small distal’ are all imprecisely defined termini, requiring subjective interpretation, and are hence prone for bias, thus strongly impeding comparison between studies. We therefore did not adopt the TICI 2c criterion, but used the oTICI version, which is essentially more conservative than mTICI, to ensure that differences in outcome between TICI 2b and TICI 3 would not be introduced by TICI 2b patients with relatively modest partial reperfusion. One may presume that our results would be even more clear-cut and pronounced if we had applied the mTICI scale.

It is plausible that remaining distal branch occlusions and associated perfusion deficits may lead to larger infarcts, and are therefore associated with less neurologic benefit and higher postinterventional NIHSS scores. Our data indicate that persistent treatment strategies may be warranted to target such distal occlusions even when recanalization of the primary proximal occlusion was ‘successful’ according to presently accepted standards. Increasingly flexible and smaller aspiration catheters and thrombectomy devices are being developed, which may be (or eventually become) suitable tools to approach blocked segments beyond M2. In addition, intra-arterial application of thrombolytic drugs after MTE may be reconsidered as an option for remote or small branch occlusions that are otherwise inaccessible. TICI 3 was associated with shorter hospital stays, which suggests that such strategies may also be cost-effective. Obviously, however, the associated risks will have to be reasonably low so as not to jeopardize the potential benefit already achieved by treatment of the primary occlusion.

In the wake of the tremendous success of MTE and stent retrievers, diverse dedicated thrombectomy devices and highly flexible, large-lumen distal access catheters for direct aspiration techniques have been developed and are being promoted by economic competitors. Virtually all of these devices now achieve TICI 2b/3 recanalization rates exceeding 80–90%. In the light of the present data, time may have come for a more ambitious definition of ‘success’ that places greater weight on the achievable rate of TICI 3. This, of course, does not disqualify TICI 2b scores as a ‘failure’, as there can be different grades of success, and there is no compelling need for rigorous dichotomization.

It has been demonstrated, based on preinterventional susceptibility-weighted MRI, that occlusions in LVO strokes are typically unilocular in >90% of patients— that is, without additional involvement of distal branches.21 This implies that most distal branch occlusions seen after MTE are due to thrombus fragmentation and distal embolization that occurs in the course of the endovascular procedure. The achievable rate of TICI 3 can therefore be viewed as a measure of safety (rather than effectiveness) of MTE devices and techniques. It may thus also be used as an informative, clinically relevant parameter to compare preventive measures against thrombus dislocation and distal embolization (eg, balloon-equipped guiding catheters vs distal aspiration catheters vs both).

In a recently published abstract, Zaidat et al22 proposed the rate of FP TICI 3— that is, the rate of complete reperfusion achieved with one single pass of the thrombectomy device- as a criterion for evaluating thrombectomy results. These authors examined a mixed population including patients with carotid T and MCA occlusions, and reported that patients with FP TICI 3 had significantly better outcomes than patients with TICI 3 after multiple passes (MP TICI 3), and even that patients with FP TICI 2b had better outcomes than patients with MP TICI 3. Consequently, these authors emphasized the importance of ‘first-pass’ success. However, FP TICI 3 was much rarer in carotid T than in MCA occlusion in that study, and data were not stratified according to occlusion site or corrected for this potential confounder, which might account for the apparently strong impact of ‘FP’ successes. Moreover, unless studied in dedicated prospective designs, procedures terminated after a single pass will generally be associated with relatively good technical results (ie, favorable TICI scores), because otherwise additional passes would normally be conducted.

FP recanalization may thus appear to be associated with relatively favorable outcome in univariate analysis (as in our data), but this needs to be corrected for recanalization grade. Accordingly, in our study of patients with MCA occlusion only, single-pass success, in contrast to TICI 3 and SORT, was not an independent predictor of outcome parameters in the adjusted multivariate regression models. This remained so even when SORTs were excluded from the models to test whether FP might have substantial impact by virtue of its association with shorter SORTs. Our data thus indicate that it is clinically relevant to obtain TICI 3, but suggest that it is not decisive if this is achieved by one pass, multiple passes, or perhaps other techniques such as IA rt-PA. Nevertheless, FP TICI 3 would obviously be preferable to MP TICI 3, particularly if tackling distal occlusions to ‘force’ TICI 3 is turns out to be significantly more risky than the established techniques for larger proximal vessels. We therefore agree with Zaidat et al that the rate of FP successes may be a valuable additional measure, providing information about MTE efficacy, but believe that this should be viewed independently from the TICI 3 rate, depending on the respective clinical or technical context.

Our study has some limitations. First, it is retrospective and observational. However, we were able to include almost all consecutive, successfully recanalized patients from a large cohort with a defined LVO pattern, leaving little possibility for relevant biases.

Second, outcome data are based on NIHSS scores and not on mid-term functional mRS scores, the most commonly used outcome measure in contemporary stroke research. However, NIHSS scores, as a dedicated neurologic scoring system, reflect more directly the neurologic impact of stroke-induced brain damage, and the benefit of therapies that strive to mitigate that damage, which is the relevant issue here. NIHSS scores and, in particular, early NIHSS scores, have been shown to provide greater statistical power than disability scales such as the mRS or the Barthel Index to ascertain benefits of acute stroke therapies, making them particularly suitable for the purpose of our study.16 ,17 Mid-term mRS scores, in contrast, are more prone to be confounded by comorbidities and post-stroke complications, particularly in older patients,23 who comprised a substantial proportion of our sample (32.3%, n=85) owing to the liberal eligibility criteria for MTE in our institution, which do not include an age limit.

Third, postinterventional NIHSS scores were assessed at discharge and not at a fixed time after the stroke. However, while the post-stroke neurologic status generally improves over time, TICI 3 patients had shorter hospital stays, so that any time dependency of NIHSS outcome would have attenuated rather than artificially introduced the better outcome of TICI 3 vs TICI 2b patients.

Fourth, the distinctly better outcome of TICI 3 patients suggests that endovascular strategies may be warranted that aim at TICI 3. Elucidating the risks that may be associated with such strategies, however, is beyond the scope of this study. Moreover, TICI scores do not discriminate between persisting occlusions according to the functional ‘eloquence’ of the dependent tissue. Further research is therefore required to evaluate the risk:benefit ratio of such strategies, and treatment decisions will probably have to be customized in any individual patient depending on the respective sites of persisting distal occlusions.