Benchmarking the Extent and Speed of Reperfusion: First Pass TICI 2c-3 Is a Preferred Endovascular Reperfusion Endpoint

Abstract

Background and Purpose: End-of-procedure substantial reperfusion [modified Treatment in Cerebral Ischemia (mTICI) 2b-3], the leading endpoint for thrombectomy studies, has several limitations including a ceiling effect, with recent achieved rates of ~90%. We aimed to identify a more optimal definition of angiographic success along two dimensions: (1) the extent of tissue reperfusion, and (2) the speed of revascularization. Methods: Core-lab adjudicated TICI scores for the first three passes of EmboTrap and the final all-procedures result were analyzed in the ARISE II multicenter study. The clinical impact of extent of reperfusion and speed of reperfusion (first-pass vs. later-pass) were evaluated. Clinical outcomes included 90-day functional independence [modified Rankin Scale (mRS) 0-2], 90-day freedom-from-disability (mRS 0-1), and dramatic early improvement [24-h National Institutes of Health Stroke Scale (NIHSS) improvement ≥ 8 points]. Results: Among 161 ARISE II subjects with ICA or MCA M1 occlusions, reperfusion results at procedure end showed substantial reperfusion in 149 (92.5%), excellent reperfusion in 121 (75.2%), and complete reperfusion in 79 (49.1%). Reperfusion rates on first pass were substantial in 81 (50.3%), excellent reperfusion in 62 (38.5%), and complete reperfusion in 44 (27.3%). First-pass excellent reperfusion (first-pass TICI 2c-3) had the greatest nominal predictive value for 90-day mRS 0-2 (sensitivity 58.5%, specificity 68.6%). There was a progressive worsening of outcomes with each additional pass required to achieve TICI 2c-3. Conclusions: First-pass excellent reperfusion (TICI 2c-3), reflecting rapid achievement of extensive reperfusion, is the technical revascularization endpoint that best predicted functional independence in this international multicenter trial and is an attractive candidate for a lead angiographic endpoint for future trials. Clinical Trial Registration: http://www.clinicaltrials.gov, identifier NCT02488915.

Keywords: brain ischaemia; cerebral infacrction; intra-arterial therapy; mechanical thrombectomy; reperfusion; reperfusion grading; stent retriever.

Figure 1

Distribution of 90-day mRS scores comparing first-pass reperfusion vs. multiple-pass reperfusion. Results are shown for (A) final TICI 2b: median 90-day mRS scores were 1 (IQR 0-3) vs. 3 (IQR 2–4) for the first-pass group vs. the multiple-pass group (P = 0.04); (B) final TICI 2c: median 90-day mRS scores were 0 (IQR 0–2) vs. 2 (IQR 1–4) for the first-pass group vs. the multiple-pass group (P = 0.004); and (C) final TICI 3 patients: median 90-day mRS scores were 1 (IQR 0–2) vs. 2 (IQR 1–5) for the first-pass group vs. the multiple-pass group (P = 0.01).

Figure 2

Box-whisker plots showing median 90-day mRS vs. final TICI grade. There are significantly lower mRS scores with greater final reperfusion (P < 0.05; Jonckheere-Terpstra trend test).

Figure 3

90-day outcomes vs. the number of passes required to reach final TICI 2c-3 reperfusion. (A) 90-day mRS: There are significantly lower mRS scores with fewer passes (P = 0.0001; Jonckheere-Terpstra trend test). (B) 90-day mRS 0–2: There are progressively lower rates of good outcome with increasing number of passes (P = 0.005; Chi-squared test for trend). Asterisk indicates significant difference compared to non-reperfusers (final TICI 0-2a). (C) 90-day mRS 0–1: There are progressively lower rates of excellent outcome with increasing number of passes (P = 0.003; Chi-squared test for trend). Asterisk indicates significant difference compared to non-reperfusers (final TICI 0-2a).