Sebastian Bellwald

Direct Mechanical Intervention Versus Bridging Therapy in Stroke Patients Eligible for Intravenous Thrombolysis: A Pooled Analysis of 2 Registries

Background and Purpose— Randomized controlled trials have shown that mechanical thrombectomy (MT) plus best medical treatment improves outcome in stroke patients with large-vessel occlusion in the anterior circulation. Whether direct MT is equally effective as bridging thrombolysis (intravenous thrombolysis plus MT) in intravenous thrombolysis eligible patients remains unclear. Methods— We compared clinical and radiological outcomes at 3 months in 249 bridging patients with 111 patients receiving direct MT for large-vessel occlusion anterior circulation stroke from 2 prospective registries (study period Essen: June 2012 to August 2013, Bern February 2009 to August 2014). We matched all patients from the direct MT group who would have qualified for intravenous thrombolysis with controls from the bridging group, using multivariate and propensity score methods. Subgroup analyses for internal carotid artery occlusions were performed. Results— Baseline characteristics did not differ between the direct MT group and bridging cohort, except for higher rates of coronary heart disease (P=0.029) and shorter intervals from onset to endovascular therapy (P<0.001) in the MT group. Functional outcome, mortality, and intracerebral hemorrhage did not differ, neither in univariate nor after multivariate and propensity score matching. However, in patients with internal carotid artery occlusion, mortality in the direct cohort was significantly lower. Conclusions— In this matched-pair analysis, there was no difference in outcome in patients with large-vessel occlusion anterior circulation stroke treated with direct MT compared with those treated with bridging thrombolysis; however, mortality in patients with internal carotid artery occlusion treated with direct MT was significantly lower than after bridging thrombolysis. Randomized trials comparing direct MT with bridging therapy are needed.

Systematic review and meta-analysis on outcome differences among patients with TICI2b versus TICI3 reperfusions: success revisited

Objective A reperfusion quality of thrombolysis in cerebral infarction (TICI)≥2b has been set as the therapeutic angiography target for interventions in patients with acute ischaemic stroke. This study addresses whether the distinction between TICI2b and TICI3 reperfusions shows a clinically relevant difference on functional outcome. Methods A systematic literature review and meta-analysis was carried out and presented in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria to test the primary hypothesis that TICI2b and TICI3 reperfusions are associated with different rates of modified Rankin Scale (mRS) ≤2 at day 90. Secondary endpoints included rates of haemorrhagic transformations, mortality and excellent functional outcome (mRS ≤1). Summary estimates of ORs (sOR) with 95% CI were calculated using the inverse variance heterogeneity model accounting for multiple true effect sizes. Results Fourteen studies on 2379 successfully reperfused patients were included (1131 TICI3, 1248 TICI2b). TICI3 reperfusions were associated with higher rates of functional independence (1.74, 95% CI 1.44 to 2.10) and excellent functional outcomes (2.01, 95% CI 1.60 to 2.53), also after including adjusted estimates. The safety profile of patients with TICI3 was superior, as demonstrated by lower rates of mortality (sOR 0.59, 95% CI 0.37 to 0.92) and symptomatic intracranial haemorrhages (sOR 0.42, 95% CI 0.25 to 0.71). Conclusion TICI3 reperfusions are associated with superior outcome and better safety profiles than TICI2b reperfusions. This effect seems to be independent of time and collaterals. As reperfusion quality is the most important modifiable predictor of patients’ outcome, a more conservative definition of successful therapy and further evaluation of treatment approaches geared towards achieving TICI3 reperfusions are desirable.

Rates and Quality of Preinterventional Reperfusion in Patients With Direct Access to Endovascular Treatment.

Background and Purpose— Preinterventional reperfusion before endovascular treatment (ET) is a benefit of bridging with intravenous tPA (tissue-type plasminogen activator). However, detailed data on reperfusion quality and rates of obviating ET in a cohort of patients with immediate access to ET is lacking. Purpose of this analysis was to evaluate prevalence and quality of preinterventional reperfusion in mothership patients. Methods— All mothership patients (n=627) from a prospective registry subjected to angiography with an intention to perform ET were reviewed. Preinterventional change of occlusion site (COS) was categorized into COS with Thrombolysis in Cerebral Infarction (TICI) 0/1, COS with TICI ≥2a, COS with TICI ≥2b, and COS with perfusion worsening. Predictors and clinical relevance were evaluated using multivariable logistic regression and results are displayed as adjusted odds ratios (aOR) and corresponding 95% confidence intervals (95% CI). Results— Prevalence of COS in all patients was 10.7% (95% CI, 8.3%–13.1%), subdividing into 2.7% COS with TICI 0/1, 6.2% COS with ≥TICI 2a (including 2.9% with TICI ≥2b), and 1.8% COS with perfusion worsening. Factors related to COS with ≥TICI 2a were intravenous tPA (aOR, 11.98; 95% CI, 4.5–31.6), cardiogenic thrombus origin (aOR, 2.3; 95% CI, 1.1–4.6), and thrombus length (aOR per 1 mm increase 0.926; 95% CI, 0.87–0.99). Additional ET was performed despite COS with ≥TICI 2a in 51.3%. COS with ≥TICI 2a showed a tendency for favorable outcomes (modified Rankin Scale, ⩽2; aOR, 2.65; 95% CI, 0.98–7.17). Rates of COS with ≥TICI 2a were particularly low in internal carotid artery and proximal M1 occlusions (2.2%; 95% CI, 0.9%–5%), where intravenous tPA was associated with perfusion worsening (aOR, 4.33; 95% CI, 1.12–16.80). Conclusions— Prevalence of preinterventional reperfusion is non-negligible in patients with direct access to ET and is clearly favored by intravenous tPA treatment. However, it is often incomplete and often requires additional ET. Preinterventional reperfusion of internal carotid artery and proximal M1 occlusions is rare and usually of low quality, where intravenous tPA may also promote perfusion worsening.

Multivessel Occlusion in Patients Subjected to Thrombectomy: Prevalence, Associated Factors, and Clinical Implications

Background and Purpose— Patients with embolic large-vessel occlusion may present with additional coincidental acute occlusions within or distant from the involved territory, referred to as multivessel occlusion (MVO). Purpose of this study was to assess prevalence of MVO, associated factors, and clinical relevance in patients undergoing endovascular stroke treatment. Methods— Image data of consecutive endovascular candidates (n=720) with direct access to angiography were extracted from a prospective registry. Prevalence of MVO was assessed with multimodal magnetic resonance imaging/computed tomography and confirmed by intra-arterial angiography. Explorative analysis of associated factors and clinical relevance was evaluated using multivariable logistic regression including variables with P<0.15 in univariate comparison. Good functional outcome was defined as modified Rankin Scale score ⩽2 at day 90. Results— MVO was present in 10.7% of patients (95% confidence interval [CI], 6.4%–13.0%). Two, 3, and 4 concomitant occlusions were found in 80.5%, 16.9%, and 2.6% of MVO cases, respectively. Detection rate on initial radiological report was 54.5%. Downstream MVO was present in around one third of MVO (n=27/77, 35.1%), whereas all other MVO (n=50/77, 64.9%) occurred in different territories. Independent factors related to MVO were statin treatment (adjusted odds ratio [aOR], 0.477; 95% CI, 0.276–0.827), higher systolic blood pressure (aOR per mm Hg increase, 1.014; 95% CI, 1.005–1.023), and primary occlusion site M2 (aOR, 1.870; 95% CI, 1.103–3.170). MVO was related to lower rates of successful reperfusion (aOR, 0.549; 95% CI, 0.316–0.953) and lower rates of good functional outcome (aOR, 0.437; 95% CI, 0.207–0.923). Conclusions— Every tenth patient subjected to angiography for endovascular stroke treatment experienced MVO in our series, and only half were prospectively identified on preinterventional diagnostic imaging. Patients with MVO had higher baseline systolic blood pressure and were less often medicated with statins, an observation that warrants external validation and evaluation regarding causality. Occurrence of MVO has implication for treatment decisions, negatively affects endovascular treatment success, and is predictive of worse clinical outcome.

Association of anemia and hemoglobin decrease during acute stroke treatment with infarct growth and clinical outcome.

Background and purpose Anemia is associated with worse outcome in stroke, but the impact of anemia with intravenous thrombolysis or endovascular therapy has hardly been delineated. The aim of this study was to analyze the role of anemia on infarct evolution and outcome after acute stroke treatment. Methods 1158 patients from Bern and 321 from Los Angeles were included. Baseline data and 3 months outcome assessed with the modified Rankin Scale were recorded prospectively. Baseline DWI lesion volumes were measured in 345 patients and both baseline and final infarct volumes in 180 patients using CT or MRI. Multivariable and linear regression analysis were used to determine predictors of outcome and infarct growth. Results 712 patients underwent endovascular treatment and 446 intravenous thrombolysis. Lower hemoglobin at baseline, at 24h, and nadir until day 5 predicted poor outcome (OR 1.150–1.279) and higher mortality (OR 1.131–1.237) independently of treatment. Decrease of hemoglobin after hospital arrival, mainly induced by hemodilution, predicted poor outcome and had a linear association with final infarct volumes and the amount and velocity of infarct growth. Infarcts of patients with newly observed anemia were twice as large as infarcts with normal hemoglobin levels. Conclusion Anemia at hospital admission and any hemoglobin decrease during acute stroke treatment affect outcome negatively, probably by enlarging and accelerating infarct growth. Our results indicate that hemodilution has an adverse effect on penumbral evolution. Whether hemoglobin decrease in acute stroke could be avoided and whether this would improve outcome would need to be studied prospectively.

Impact of smoking on stroke outcome after endovascular treatment.

Background Recent studies suggest a paradoxical association between smoking status and clinical outcome after intravenous thrombolysis (IVT). Little is known about relationship between smoking and stroke outcome after endovascular treatment (EVT). Methods We analyzed data of all stroke patients treated with EVT at the tertiary stroke centre of Berne between January 2005 and December 2015. Using uni- and multivariate modeling, we assessed whether smoking was independently associated with excellent clinical outcome (modified Rankin Scale (mRS) 0–1) and mortality at 3 months. In addition, we also measured the occurrence of symptomatic intracranial hemorrhage (sICH) and recanalization. Results Of 935 patients, 204 (21.8%) were smokers. They were younger (60.5 vs. 70.1 years of age, p<0.001), more often male (60.8% vs. 52.5%, p = 0.036), had less often from hypertension (56.4% vs. 69.6%, p<0.001) and were less often treated with antithrombotics (35.3% vs. 47.7%, p = 0.004) as compared to nonsmokers. In univariate analyses, smokers had higher rates of excellent clinical outcome (39.1% vs. 23.1%, p<0.001) and arterial recanalization (85.6% vs. 79.4%, p = 0.048), whereas mortality was lower (15.6% vs. 25%, p = 0.006) and frequency of sICH similar (4.4% vs. 4.1%, p = 0.86). After correcting for confounders, smoking still independently predicted excellent clinical outcome (OR 1.758, 95% CI 1.206–2.562; p<0.001). Conclusion Smoking in stroke patients may be a predictor of excellent clinical outcome after EVT. However, these data must not be misinterpreted as beneficial effect of smoking due to the observational study design. In view of deleterious effects of cigarette smoking on cardiovascular health, cessation of smoking should still be strongly recommended for stroke prevention.