Sandra Boned

Association Between Time to Reperfusion and Outcome Is Primarily Driven by the Time From Imaging to Reperfusion

Background and Purpose— A progressive decline in the odds of favorable outcome as time to reperfusion increases is well known. However, the impact of specific workflow intervals is not clear. Methods— We studied the mechanical thrombectomy group (n=103) of the prospective, randomized REVASCAT (Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset) trial. We defined 3 workflow metrics: time from symptom onset to reperfusion (OTR), time from symptom onset to computed tomography, and time from computed tomography (CT) to reperfusion. Clinical characteristics, core laboratory-evaluated Alberta Stroke Program Early CT Scores (ASPECTS) and 90-day outcome data were analyzed. The effect of time on favorable outcome (modified Rankin scale, 0–2) was described via adjusted odds ratios (ORs) for every 30-minute delay. Results— Median admission National Institutes of Health Stroke Scale was 17.0 (14.0–20.0), reperfusion rate was 66%, and rate of favorable outcome was 43.7%. Mean (SD) workflow times were as follows: OTR: 342 (107) minute, onset to CT: 204 (93) minute, and CT to reperfusion: 138 (56) minute. Longer OTR time was associated with a reduced likelihood of good outcome (OR for 30-minute delay, 0.74; 95% confidence interval [CI], 0.59–0.93). The onset to CT time did not show a significant association with clinical outcome (OR, 0.87; 95% CI, 0.67–1.12), whereas the CT to reperfusion interval showed a negative association with favorable outcome (OR, 0.72; 95% CI, 0.54–0.95). A similar subgroup analysis according to admission ASPECTS showed this relationship for OTR time in ASPECTS<8 patients (OR, 0.56; 95% CI, 0.35–0.9) but not in ASPECTS≥8 (OR, 0.99; 95% CI, 0.68–1.44). Conclusions— Time to reperfusion is negatively associated with favorable outcome, being CT to reperfusion, as opposed to onset to CT, the main determinant of this association. In addition, OTR was strongly associated to outcome in patients with low ASPECTS scores but not in patients with high ASPECTS scores. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01692379.

Impact of Time to Treatment on Tissue-Type Plasminogen Activator–Induced Recanalization in Acute Ischemic Stroke

Background and Purpose— Although tissue-type plasminogen activator (tPA) efficacy depends on time, it is unknown whether its effect on recanalization is time dependent. Information about likelihood of successful recanalization as a function of time to treatment may improve patient selection for advanced reperfusion strategies. We aimed to identify the impact of time to treatment on tPA-induced recanalization in patients with acute ischemic stroke. Methods— Consecutive patients with intracranial acute occlusion treated with intravenous tPA underwent transcranial Doppler examination before and 1 hour after tPA administration. Patients were categorized according to occlusion localization in proximal and distal occlusion. Sequential analysis of recanalization according to time to treatment was performed for every 30-minute cutoff point. Results— Overall (n=508), 54.3% had proximal and 45.7% had distal occlusion. Median time to treatment was 171.4±61.9 minutes, and 5.9% were treated >270 minutes. Recanalization occurred in 36.1% of patients. There was no linear association between time to treatment and time to recanalization, but sequential analysis showed that patients treated >270 minutes had a lower recanalization rate. Lower National Institutes of Health Stroke Scale score on admission (odds ratio [OR], 0.305; 95% confidence interval [CI], 0.1–0.933) and time to treatment ⩽270 minutes (OR, 0.995; 95% CI, 0.99–0.999) emerged as independent predictors of recanalization. In patients with proximal occlusion, 41.8% recanalized. Time to treatment >90 minutes was associated with lower recanalization rate. However, only younger age (OR, 0.975; 95% CI, 0.952–0.999) and lower baseline National Institutes of Health Stroke Scale score (OR, 0.921; 95% CI, 0.855–0.993) independently predicted recanalization. In distal occlusion patients, male sex was the only independent predictor of recanalization (OR, 0.416; 95% CI, 0.195–0.887). None recanalized >270 minutes. Conclusions— The effect of tPA on recanalization may decrease over time. Treatment >270 minutes predicted lack of recanalization, especially in distal occlusions.

Left Atria Strain Is a Surrogate Marker for Detection of Atrial Fibrillation in Cryptogenic Strokes

After complete diagnostic workup, a quarter of ischemic strokes are regarded as undetermined pathogenesis at discharge with a substantial rate of mortality in some cases.1 Paroxysmal atrial fibrillation (PAF) is the most frequent occult cause resulting in significant morbidity and costs when is under diagnosed.2 Recent studies have shown that extending the cardiac monitoring duration with subcutaneous implantable monitors and selecting patients for prolonged monitoring significantly increased the PAF detection in ischemic strokes.3 The left atria volume (LAv) has been used to assess the left atrial function. Nevertheless, the left atria dimension is predictive of stroke but become nonsignificant after adjustment for the older age.4 The left atria function can be also obtained by the analysis of the left atria walls deformation, also called strain of the left atria. The speckle tracking is an echocardiographic technique that uses standard B-mode images for the analysis of the acoustic backscatter generated by the ultrasound beam. The changes between speckles are assumed to represent the strain.5 The published intraobserver and interobserver variability of left atria strain (LAS) is 7.8%, and 8.9%, respectively.6 The LAS profile has been previously described in patients with PAF and in correlation with CHADS2 score (hypertension >140/90 mm Hg, age ≥75, diabetes, prior stroke),7 but it has never been studied in cryptogenic ischemic strokes. We aimed to describe the left atria functionality assessed by LAS parameter in cryptogenic strokes to improve the detection of occult PAF. With the purpose to obtain the best LAS cutoff point to differentiate patients with and without PAF, we planned the comparison as a case–control study. Accordingly, the selection of patients without PAF (non-PAF group) was made considering consecutive patients with cryptogenic stroke after complete workup evaluation with no PAF episodes in 3-year cardiac monitoring with Holter …

Poor Collateral Circulation Assessed by Multiphase Computed Tomographic Angiography Predicts Malignant Middle Cerebral Artery Evolution After Reperfusion Therapies

Background and Purpose— Collateral circulation (CC) has been associated with recanalization, infarct volume, and clinical outcome in patients undergoing acute reperfusion therapies. However, its relationship with the development to malignant middle cerebral artery infarction (mMCAi) has not been evaluated. Our aim was to determine the impact of CC using multiphase computed tomographic angiography (during the acute stroke phase in the prediction of mMCAi. Methods— Patients with consecutive acute stroke with <4.5 hours who were evaluated for reperfusion therapies and presented with an M1-MCA or terminal internal carotid artery occlusion by CTA were included. CC was evaluated on 6 grades by multiphase CTA according to the University of Calgary CC Scale; CC status was defined as poor (grades, 0–3) or good (grades, 4–5). The mMCAi was defined according to clinical and radiological criteria. Recanalization was assessed with transcranial Doppler at 24 hours and final Thrombolysis in Brain Ischemia score ≥2b in patients undergoing endovascular reperfusion treatment. Results— Eighty-two patients were included. Mean age was 65.1±13.83 years, median baseline National Institutes of Health Stroke Scale score was 18 (interquartile range, 13–20), and 67.9% M1 and 32.1% terminal internal carotid artery occlusions. Fifty-three patients received endovascular reperfusion treatment. Fifteen patients developed mMCAi. In the univariate analysis, patients with mMCAi had lower CC scores (2.29 versus 3.71; P=0.001). Endovascular reperfusion treatment was associated with lower rate of mMCAi development than only intravenous reperfusion treatment (9.4% versus 29.6%; P=0.028). Patients with poor CC had higher risk of developing mMCAi (13% versus 2%; P=0.001). On the multivariate analysis adjusted by age, vessel occlusion, baseline National Institutes of Health Stroke Scale, and recanalization, the presence of poor CC by multiphase CTA was the only independent predictor of mMCAi (P=0.048; odds ratio, 9.72; 95% confidence interval, 1.387–92.53). Conclusions— CC assessment by multiphase CTA independently predicts malignant MCA infarction progression. In patients with persistent occlusion after reperfusion therapies, the presence of poor CC may improve the early mMCAi detection and management.

Endovascular treatment improves cognition after stroke A secondary analysis of REVASCAT trial

Objective: To investigate the effect of endovascular treatment on cognitive function as a prespecified secondary analysis of the REVASCAT (Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours) trial. Methods: REVASCAT randomized 206 patients with anterior circulation proximal arterial occlusion stroke to Solitaire thrombectomy or best medical treatment alone. Patients with established dementia were excluded from enrollment. Cognitive function was assessed in person with Trail Making Test (TMT) Parts A and B at 3 months and 1 year after randomization by an investigator masked to treatment allocation. Test completion within 5 minutes, time of completion (seconds), and number of errors were recorded. Results: From November 2012 to December 2014, 206 patients were enrolled in REVASCAT. TMT was assessed in 82 of 84 patients undergoing thrombectomy and 86 of 87 control patients alive at 3 months and in 71 of 79 patients undergoing thrombectomy and 72 of 78 control patients alive at 1 year. Rates of timely TMT-A completion were similar in both treatment arms, although patients undergoing thrombectomy required less time for TMT-A completion and had higher rates of error-free TMT-A performance. Thrombectomy was also associated with a higher probability of timely TMT-B completion (adjusted odds ratio 3.17, 95% confidence interval 1.51–6.66 at 3 months; and adjusted ratio 3.66, 95% confidence interval 1.60–8.35 at 1 year) and shorter time for TMT-B completion. Differences in TMT completion times between treatment arms were significant in patients with good functional outcome but not in those who were functionally dependent (modified Rankin Scale score >2). Poorer cognitive outcomes were significantly associated with larger infarct volume, higher modified Rankin Scale scores, and worse quality of life. Conclusions: Thrombectomy improves TMT performance after stroke, especially among patients who reach good functional recovery. ClinicalTrials.gov identifier: NCT01692379. Classification of evidence: This study provides Class I evidence that for patients with stroke from acute anterior circulation proximal arterial occlusion, thrombectomy improves performance on the TMT at 3 months.

Admission CT perfusion may overestimate initial infarct core: the ghost infarct core concept.

Background Identifying infarct core on admission is essential to establish the amount of salvageable tissue and indicate reperfusion therapies. Infarct core is established on CT perfusion (CTP) as the severely hypoperfused area, however the correlation between hypoperfusion and infarct core may be time-dependent as it is not a direct indicator of tissue damage. This study aims to characterize those cases in which the admission core lesion on CTP does not reflect an infarct on follow-up imaging. Methods We studied patients with cerebral large vessel occlusion who underwent CTP on admission but received endovascular thrombectomy based on a non-contrast CT Alberta Stroke Program Early CT Score (ASPECTS) >6. Admission infarct core was measured on initial cerebral blood volume (CBV) CTP and final infarct on follow-up CT. We defined ghost infarct core (GIC) as initial core minus final infarct >10 mL. Results 79 patients were studied. Median National Institutes of Health Stroke Scale (NIHSS) score was 17 (11–20), median time from symptoms to CTP was 215 (87–327) min, and recanalization rate (TICI 2b–3) was 77%. Thirty patients (38%) presented with a GIC >10 mL. GIC >10 mL was associated with recanalization (TICI 2b–3: 90% vs 68%; p=0.026), admission glycemia (<185 mg/dL: 42% vs 0%; p=0.028), and time to CTP (<185 min: 51% vs >185 min: 26%; p=0.033). An adjusted logistic regression model identified time from symptom to CTP imaging <185 min as the only predictor of GIC >10 mL (OR 2.89, 95% CI 1.04 to 8.09). At 24 hours, clinical improvement was more frequent in patients with GIC >10 mL (66.6% vs 39%; p=0.017). Conclusions CT perfusion may overestimate final infarct core, especially in the early time window. Selecting patients for reperfusion therapies based on the CTP mismatch concept may deny treatment to patients who might still benefit from reperfusion.

Improving the Evaluation of Collateral Circulation by Multiphase Computed Tomography Angiography in Acute Stroke Patients Treated with Endovascular Reperfusion Therapies.

Good collateral circulation (CC) is associated with favorable outcomes in acute stroke, but the best technique to evaluate collaterals is controversial. Single-phase computed tomography angiography (sCTA) is widely used but lacks temporal resolution. We aim to compare CC evaluation by sCTA and multiphase CTA (mCTA) as predictors of outcome in endovascular treated patients. Methods: Consecutive endovascular treated patients with M1 middle cerebral artery (MCA) or terminal intracranial carotid artery (TICA) occlusion confirmed by sCTA were included. Two more CTA acquisitions with 8- and 16-second delays were performed for mCTA. Endovascular thrombectomy was performed independently of the CC status according to a local protocol [Alberta Stroke Program Early CT score (ASPECTS) >6, modified Rankin scale (mRS) score <3]. CC on sCTA and mCTA were compared. Results: 108 patients were included. Their mean age was 69.6 ± 13 years and their median National Institutes of Health Stroke Scale (NIHSS) score was 17 (interquartile range 8). 79 (73.1%) had M1 MCA and 29 (26.9%) TICA occlusions. The mean time from symptom onset to CTA was 146.8 ± 96.5 min. On sCTA, 50.9% patients presented good CC vs. 57.5% on mCTA. Good CC status in both sCTA and mCTA had a lower 24-hour infarct volume (27.4 vs. 74.8 cm3 on sCTA, p = 0.04; 17.2 vs. 97.8 cm3 on mCTA, p < 0.01). However, only good CC on mCTA was associated with lower 24-hour (5 vs. 8.5, p = 0.04) and median discharge NIHSS (2 vs. 4.5, p = 0.04) scores and functional independency (mRS score <3) at 3 months (76.9 vs. 23.1%, p < 0.01). In a logistic regression model including age, NIHSS, ASPECTS and recanalization, only age (OR 0.96, 95% CI 0.93-0.99, p = 0.02) and good CC on mCTA (OR 5, 95% CI 1.99-12.6, p < 0.01) were independent predictors of functional outcome at 3 months. Conclusion: CC evaluation by mCTA is a better prognostic marker than CC evaluation by sCTA for clinical and functional endpoints in acute stroke patients treated with endovascular thrombectomy.

Direct transfer to angiosuite to reduce door-to-puncture time in thrombectomy for acute stroke

Objective To evaluate direct transfer to the angiosuite protocol of patients with acute stroke, candidates for endovascular treatment (EVT). Methods We studied workflow metrics of all patients with stroke who had undergone EVT in the past 12 months. Patients followed three protocols: direct transfer to emergency room (DTER), CT room (DTCT) or angiosuite (DTAS, only last 6 months if admission National Institute of Health Stroke Scale (NIHSS) score >9 and time from onset <4.5 hours) according to staff/suite availability. DTAS patients underwent cone-beam CT before femoral puncture. Dramatic clinical improvement was defined as 10 NIHSS points drop at 24 hours. Results 201 patients were included: 87 DTER (43.3%), 74 DTCT (36.8%), 40 DTAS (19.9%). Ten DTAS patients (25%) did not receive EVT: 3 (7.5%) showed intracranial hemorrhage on cone-beam CT and 7 (17.5%) did not show an occlusion on angiography. Mean door-to-puncture (D2P) time was shorter in DTAS (17±8 min) than DTCT (60±29 min; p<0.01). D2P was longer in DTER (90±53 min) than in the other protocols (p<0.01). For outcome analyses only patients who received EVT were compared; no significant differences in baseline characteristics, including time from symptom-onset to admission, puncture-to-recanalization, or recanalization rate, were seen. However, time from symptom-to-puncture (DTAS: 197±72 min, DTER: 279±156, DTCT: 224±142 min; p=0.01) and symptom-to-recanalization (DTAS: 257±74, DTER: 355±158, DTCT: 279±146 min; p<0.01) were longer in the DTER group. At 24 hours, there were no differences in NIHSS score (p=0.81); however, the rate of dramatic clinical improvement was significantly higher in DTAS: 48.6% (DTER 24.1%, DTCT 27.4%); p=0.01). An adjusted model pointed to shorter onset-to-puncture time as an independent predictor of dramatic improvement (OR=1.23, 95% CI 1.13 to 133; p<0.01) Conclusion In a subgroup of patients direct transfer and triage in the angiosuite seems feasible, safe, and achieves significant reduction in hospital workflow times.

Factor seven activating protease (FSAP) predicts response to intravenous thrombolysis in acute ischemic stroke

Background Prediction of recanalization after intravenous thrombolysis could be important to direct secondary reperfusion techniques. Factor seven activating protease (FSAP) has been described to have a relevant pathophysiological role in stroke. Aim The aim is to determine whether plasma FSAP levels are associated with recanalization after tissue plasminogen activator in acute stroke. Methods FSAP antigen, activity, and FSAP-inhibitor complexes were measured in 120 acute stroke patients admitted to Hospital Vall d’Hebron with arterial occlusions, before intravenous thrombolysis. Recanalization was assessed by transcranial Doppler 2 h after thrombolysis. Predictors of recanalization were determined by logistic regression analysis and the additional predictive value of FSAP over them was determined by integrated discrimination improvement index. Results Complete recanalization was achieved in 31 patients. FSAP antigen levels were lower in patients achieving recanalization (8.2 (6.3–11.7) µg/mL vs. 9.8 (7.6–12.8) µg/mL; p = 0.046). After adjustment by age, sex, and National Institutes of Health Stroke Scale, Oxfordshire Community Stroke Project (odds ratio = 0.33 (0.13–0.82), p = 0.017) and FSAP antigen (odds ratio = 3.22 (1.22–8.47), p = 0.018) were independently associated with recanalization, and the addition of FSAP improved the model discrimination (integrated discrimination improvement = 5.5% (1.4–9.7), p = 0.009). Conclusions Our study showed that lower FSAP antigen plasma levels were associated with a higher chance of arterial recanalization after tissue plasminogen activator treatment, suggesting an involvement of FSAP in tissue plasminogen activator-induced clot lysis. FSAP antigen determination might be useful in predicting tissue plasminogen activator response in stroke patients.

Phone and Video-Based Modalities of Central Blinded Adjudication of Modified Rankin Scores in an Endovascular Stroke Trial

Background and Purpose— The standard outcome measure in stroke research is modified Rankin scale (mRS) evaluated by local blinded investigators. We aimed to assess feasibility and reliability of 2 central adjudication methods of mRS in the setting of a randomized endovascular stroke trial. Methods— This is a secondary analysis derived from the Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT) trial cohort. Primary outcome was distribution of mRS at 90 days. Local evaluation was done by certified investigators masked to treatment assignment using structured face-to-face interviews. In addition, central assessment was performed by 2 independent raters via structured phone interview (n=120) and via video recordings of the face-to-face interviews with local investigators (n=106). Interrater agreement was evaluated using kappa and discordance statistics. Sensitivity analyses for the primary end point using different adjudication approaches were performed. Correlation between mRS obtained with each modality and 24-hour follow-up infarct volumes was studied. Results— Using local evaluation as the reference, higher agreement rates were noted with central video than with central phone evaluations (kw 0.92 [0.88–0.96] versus 0.77 [0.72–0.83]). Discrepancies in mRS scoring between local and central raters (phone- and video-based) were similar in both treatment allocation arms. Sensitivity analyses showed benefit of endovascular treatment irrespective of adjudication method, but higher odds ratios were observed with local evaluations. Final infarct volume was similarly correlated with mRS across all 3 evaluation modalities. Conclusions— Central adjudication of mRS is feasible, reducing interrater variability and avoiding potential problems related to lack of blinding. Our findings may have implications in the planning of future randomized acute stroke trials, especially in those including nonpharmacological interventions. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01692379.