Higher Clot Burden Research Articles

Clot Burden Score on Baseline Computerized Tomographic Angiography and Intra-Arterial Treatment Effect in Acute Ischemic Stroke.

A high clot burden score (CBS) is associated with favorable outcome after intravenous treatment for acute ischemic stroke. The added benefit of intra-arterial treatment might be less in these patients. The aim of this exploratory post hoc analysis was to assess the relation of CBS with neurological improvement and endovascular treatment effect. For 499 of 500 patients in the MR CLEAN study (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), the CBS was determined. Ordinal logistic regression models with and without main baseline prognostic variables were used to assess the association between CBS (continuous or dichotomized at CBS of 6) and a shift toward better outcome on the modified Rankin Scale. The model without main baseline prognostic variables only included treatment allocation and CBS. Models with and without a multiplicative interaction term of CBS and treatment were compared using the χ2 test to assess treatment effect modification by CBS. Higher CBS was associated with a shift toward better outcome on the modified Rankin Scale; adjusted common odds ratio per point CBS was 1.12 (95% confidence interval, 1.04-1.20]. Dichotomized CBS had an adjusted common odds ratio of 1.67 (95% confidence interval, 1.12-2.51). Both effect estimates were slightly attenuated by adding baseline prognostic variables. The addition of the interaction terms did not significantly improve the fit of the models. There was a small and insignificant increase of intra-arterial treatment efficacy in the high CBS group. A higher CBS is associated with improved outcome and may be used as a prognostic marker. We found no evidence that CBS modifies the effect of intra-arterial treatment. URL: http://www.trialregister.nl. Unique identifier: NTR1804. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN10888758.

Successful recanalization in acute basilar artery occlusion treated with endovascular therapy is independent of thrombus length

Background and purposeAs previously demonstrated, the recanalization rate and clinical outcome in patients with anterior circulation stroke treated with IV thrombolysis (IVT) depend on clot characteristics such as thrombus length...

Fibrinogen consumption is related to intracranial clot burden in acute ischemic stroke: a retrospective hyperdense artery study.

BackgroundUnderstanding the underlying mechanism of thrombus formation and its components is critical for effective prevention and treatment of ischemic stroke. The generation of thrombotic clots requires conversion of soluble fibrinogen to an insoluble fibrin network. Quantitative features of intracranial clots causing acute ischemic stroke can be studied on non-contrast enhanced CT (NECT). Here, we evaluated on-admission fibrinogen and clot burden in relation to stroke severity, final infarct volume and in-hospital mortality.MethodsWe included 132 consecutive patients with ischemic stroke and presence of hyperdense artery sign admitted within 6 h from symptom onset. Radiological parameters including clot area (corresponding to clot burden) and final infarct volume were manually determined on NECT. National Institute of Health Stroke Scale (NIHSS) was used to quantify disease severity and short-term outcome.ResultsMedian patient age was 77, 58 % were women, and 63 % had an occlusion of the proximal middle cerebral artery segment. Thrombolysis was performed in 60 % and thrombectomy in 44 %. We identified several independent associations. Higher fibrinogen levels on admission were associated with smaller clot burden (p = 0.033) and lower NIHSS on admission (p = 0.022). Patients with lower fibrinogen had a higher clot burden (p = 0.028) and greater final infarct volume (p = 0.003). Higher fibrinogen was associated with a lower risk of in-hospital death or NIHSS score >15 if discharged alive (p = 0.028).ConclusionsOur study suggests that intracranial clot burden in acute ischemic stroke is associated with fibrinogen consumption, and shows a complex relationship with disease severity, infarct size and in-hospital survival.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-1006-6) contains supplementary material, which is available to authorized users.

Relation Among Clot Burden, Right-Sided Heart Strain, and Adverse Events After Acute Pulmonary Embolism

Computed tomography pulmonary angiogram (CTPA) provides a volumetric assessment of clot burden in acute pulmonary embolism (PE). However, it is unclear if clot burden is associated with right-sided heart strain (RHS) or adverse clinical events (ACE). We prospectively enrolled Emergency Department patients with PE (in CTPA) from 2008 to 2011. We assigned 1 to 9 points as clot burden score, based on whether emboli were saddle, central, lobar, segmental, and subsegmental. We evaluated a novel score (the "CT-PASS") based on the sum (in millimeters) of the largest filling defects in the right and left pulmonary vasculature. Our primary outcome was RHS, defined by imaging (echocardiography or CTPA) or cardiac biomarkers. Our secondary outcomes included 5-day ACE. We included 271 patients (50% women), with a mean age of 59 ± 17years. Based on CTPA, 131 patients (48%) had central PE (clot burden score ≥5 points). The median CT-PASS was 9.1mm (interquartile range 4.9 to 16.4). In univariate analysis, higher clot burden (highest quartile CT-PASS) was associated with RHS (p= 0.003). In multivariate analysis, after adjusting for RHS, age, and gender, central PE (odds ratio [OR] 2.92, 95% confidence interval [CI] 1.10 to 7.81) and CT-PASS >20mm (OR 3.54, 95% CI 1.39 to 8.97) were significantly associated with ACE. However, this association of central PE with ACE was not statistically significant after excluding patients with shock index >1 (OR 2.56, 95% CI 0.62 to 10.64). In conclusion, highest quartile CT-PASS was associated with RHS and central PE and ACE, but this association was not statistically significant in hemodynamically stable PE [corrected].

Imaging Findings Associated with Space-Occupying Edema in Patients with Large Middle Cerebral Artery Infarcts.

Prominent space-occupying cerebral edema is a devastating complication occurring in some but not all patients with large MCA infarcts. It is unclear why differences in the extent of edema exist. Better knowledge of factors related to prominent edema formation could aid treatment strategies. This study aimed to identify variables associated with the development of prominent edema in patients with large MCA infarcts. From the Dutch Acute Stroke Study (DUST), 137 patients were selected with large MCA infarcts on follow-up NCCT (3 ± 2 days after stroke onset), defined as ASPECTS ≤4. Prominent edema was defined as a midline shift of ≥5 mm on follow-up. Admission patient and treatment characteristics were collected. Admission CT parameters used were ASPECTS on NCCT and CBV and MTT maps, and occlusion site, clot burden, and collaterals on CTA. Permeability on admission CTP, and day 3 recanalization and reperfusion statuses were obtained if available. Unadjusted and adjusted (age and NIHSS) odds ratios were calculated for all variables in relation to prominent edema. Prominent edema developed in 51 patients (37%). Adjusted odds ratios for prominent edema were higher with lower ASPECTS on NCCT (adjusted odds ratio, 1.32; 95% CI, 1.13-1.55) and CBV (adjusted odds ratio, 1.26; 95% CI, 1.07-1.49), higher permeability (adjusted odds ratio, 2.35; 95% CI, 1.30-4.24), more proximal thrombus location (adjusted odds ratio, 3.40; 95% CI, 1.57-7.37), higher clot burden (adjusted odds ratio, 2.88; 95% CI, 1.11-7.45), and poor collaterals (adjusted odds ratio, 3.93; 95% CI, 1.78-8.69). Extensive proximal occlusion, poor collaterals, and larger ischemic deficits with higher permeability play a role in the development of prominent edema in large MCA infarcts.

Role of anticoagulation in neurological practice.

Stroke is a common neurological disorder causing significant mortality and morbidity. The burden of stroke is much more in developing nations, particularly in India due to widely prevalent risk factors like hypertension, diabetes, smoking, metabolic syndrome and sedentary lifestyle1. The stroke burden can be reduced by taking care of modifiable risk factors and administration of preventive medications. Cardioembolic stroke (CES) is one of the subtypes of stroke occurring due to embolization from heart to intracranial vasculature. The common cardiac conditions are non-valvular atrial fibrillation (NVAF), prosthetic heart valve (PHV), dilated cardiomyopathy (DCMP), left atrial appendage thrombus and left atrial myxoma. Of all cases of cerebral infarctions, the cardioembolic stroke accounts for 14-30 per cent cases2. The prevalence of atrial fibrillation (AF) increases with age and it is around 10 per cent at 80 yr of age. AF leads to five-fold increase in risk of stroke and it causes more severe, lethal strokes due to high clot burden in major vessels and causes substantial morbidity and mortality3.

Venous Thromboembolism in Northeast Melbourne, Australia: Evaluation of Epidemiology, Risk Factors and Treatment Strategies in the Warfarin Era

AimVenous thromboembolism (VTE) is a major cause of morbidity and mortality and is estimated to cost approximately AUD$117 000 per person (Access Economics 2008). Despite advances in thrombosis management, recurrence rates remain high and management strategies are often heterogenous even within a single institution. While most studies have analysed specific aspects of VTE management, we aim to provide a holistic evaluation of real-world VTE management in the warfarin era including identifiying potential causal effects and complications.MethodRetrospective evaluation of VTE over an 18-month period, from July 2011 to December 2012, at two major hospitals in Northeast Melbourne, Australia, including demographics, provoking factors, management, complications and mortality. Comparisons were made between cancer and non-cancer populations.Result1003 patients, with median age of 63 (range 19-97) years, were identified including 26 recurrences (total 1029 episodes) - 577 (56%) pulmonary embolism (PE), 428 (42%) deep venous thrombosis (DVT). There was an overall male predominance (52%), particularly affecting the DVT subgroup (57% vs 48%, p=0.003) with no gender differences detected in the PE subgroup. 20% reported prior VTE and left limb DVT was more common (49% vs 43%, p=0.0008). The median follow up was 20 (range 10-32) months.NON-CANCER PATIENTSIn this cohort, 63% had provoked VTE and thrombophilia screen was performed in 41%. The median duration of anticoagulation was 6 and 7 months for DVT and PE respectively. The majority (90%) was on warfarin for long-term anticoagulation. 5% required further interventions – IVC filter (n=28) and thrombolysis (n=15).38% had end-of-treatment repeat imaging and residual clot was observed in 40%. Clot persistence was associated with increased recurrence risk, with an odds ratio of 2.64 (1.15 – 6.04, p=0.02). 8% had recurrent thrombosis with no difference between provoked versus unprovoked VTE (7.5% vs 9.0%, p=0.45). 5% reported grade III/IV bleeding, independent of duration of anticoagulation. Patients on enoxaparin had higher risk of bleeding (28% vs 10%, p<0.001). The all-cause mortality rate was 11%.In the sub-analysis of below knee DVT (BKDVT), 3 patients (1.5%) were subsequently diagnosed with cancer, similar prevalence to those with major VTE (1.7%), defined as proximal DVT and/or PE. BKDVT were more likely to be provoked (72% vs 55%, p<0.001) and recurrence was similar to major VTE (6.8% vs 8.7%, p=0.42) although patients with major VTE were more likely to experience grade III/IV bleeding complications (6.3% vs 1.0%, p=0.003) despite similar duration of therapy. Mortality rate in this cohort was 5.5% with no thrombosis-related deaths.CANCER PATIENTS233 (23%) patients had active malignancy at time of VTE with 14 patients (1.4%) subsequently diagnosed. Cancer patients were older (67 vs 61 years, p<0.001) and had higher clot burden with more PE (64% vs 53%, p=0.004), proximal DVT (63% vs 46%, p=0.0008) and bilateral DVT (16% vs 5%, p<0.001) compared to non-cancer patients. Patients with metastatic cancer were also more likely to have unprovoked events (p=0.015). Cancer patients were more likely to require IVC filters (9% vs 3.6%, p<0.001) and lifelong anticoagulation (35% vs 18%, p<0.001).Recurrent thrombosis (16%, p<0.001) and Grade III/IV bleeding (9%, p=0.025) were more common. However, bleeding rates in cancer patients on long-term enoxaparin were similar to warfarin. Mortality rate in the cancer patients was 63% and were related to with higher incidence of complications-related deaths (p<0.001).ConclusionVTE is associated with significant mortality, even in non-cancer patients (11%). The annual recurrence rate is 6%, with malignancy and residual clot on repeat imaging being major risk factors. Cancer patients experience more Grade III/IV bleeding complications (9% vs 5%) and had higher clot burden and all-cause mortality compared to non-cancer patients.Interestingly, BKDVT, often considered a minor VTE, had comparable rates of recurrence and subsequent cancer detection to major VTE suggesting that the investigation and treatment of BKDVT should not differ from major VTE.Further evaluation of new treatment strategies as well as clinical and laboratory risk assessments are required to improve the management for VTE. This data will serve as an important baseline for future comparison in the new era of novel oral anticoagulants. DisclosuresNo relevant conflicts of interest to declare.

P-045 The role of bridging with intravenous thrombolysis in endovascular therapy of acute ischemic stroke

BackgroundLarge vessel occlusions with a high clot burden are less likely to improve with the FDA-approved IV strategy. Endovascular therapy within the first 3 h of stroke symptom onset provides...

Abstract 3314: The Role of Bridging with Intravenous Thrombolysis in Endovascular Therapy of Acute Ischemic Stroke.

Background: Large vessel occlusions with a high clot burden are less likely to improve with the FDA-approved IV strategy. Endovascular therapy within the first 3 h of stroke symptom onset provides an effective alternative treatment in patients with large vessel occlusion. It is not clear if combination of IV thrombolysis and endovascular approach is superior to endovascular treatment alone. Methods: We retrospectively reviewed all cases of acute ischemic stroke with large vessel occlusion treated within the first 3 h stroke onset during the 2005-2010 period. First group received endovascular therapy within the first 3 h of stroke onset. Second group consisted of patients who received IV thrombolysis within the first 3 h followed by endovascular therapy. We compared the following outcomes: revascularization rates, NIHSS score at discharge, mRS at discharge and 3months, symptomatic hemorrhage rates and mortality. Results: Among 104 patients identified, 42 received combined therapy, and 62 received endovascular therapy only. The two groups had similar demographic (age and sex distribution) and vascular risk factors distribution, as well as NIHSS score on admission (14.8±4.7 and 16.0±5.3; p=0.23). We found no difference in TIMI recanalization rates (Thrombolysis in Myocardial Infarction scale score of 2 or 3) following combined or endovascular therapy alone (83.3% and 79.0%; p=0.59). A preferred outcome, defined as a mRS of 2 or less at 90 days also did not differ between the combined therapy group and the endovascular only group (37.5% and 34.5%; p=0.76). There was no difference in mortality rate (22.5% and 31.0%; p=0.36) and the rate of symptomatic intracranial hemorrhage (9.5% and 8.1%; p=0.73). There was a significant difference in mean time from symptom onset to endovascular treatment between the combined group (227±88 min) and endovascular only group (125±40 min; p&lt;0.0001).Patients with good TIMI recanalization rate of 2 or 3 showed a trend of having a better mRS at 90 days in both bridging (16.67% vs. 41.18%, p-value: 0.3813) and endovascular groups (25% vs. 34.78%, p-value: 0.7326).When analyzing the correlation of mRS at 90 days with the site of occlusion, patients in the bridging group showed a trend of a better outcome when the site of occlusion was ICA (33.3% vs 30%) and MCA (66.67% vs. 27.59%) and worse outcome when the site of occlusion was in the posterior circulation (26.32% vs. 50%), however, these results were not statistically significant (p-values: 0.1735&amp; 0.5366). Conclusion: Combining IV thrombolysis and endovascular therapy achieves similar rates of clinical outcomes, revascularization rates, complications and mortality rates, when compared with endovascular treatment alone. The combined therapy, however, significantly delays initiation of endovascular treatment. A randomized prospective trial comparing both treatment strategies in acute ischemic stroke is warranted

P-005 Is bridging with intravenous thrombolysis of any benefit in endovascular therapy of acute ischemic stroke?

BackgroundLarge vessel occlusions with a high clot burden are less likely to improve with presently accepted and FDA-approved intravenous thrombolysis (IV) strategy. Endovascular therapy within the first 3 h of...

Recent Advances in Chronic Thromboembolic Pulmonary Hypertension

Surgical excellence in pulmonary thromboendarterectomy (PTE) for chronic thromboembolic pulmonary hypertension (CTEPH) has begun to spread around the world. The perioperative mortality for this procedure is typically under 10%. The maximal benefit from PTE is derived in those patients who have a high proximal clot burden that is surgically accessible, as outlined by the Jamieson classification. Residual pulmonary hypertension after successful PTE is common and increasingly is managed with maintenance oral pulmonary vasodilator therapy such as endothelin antagonists, phosphodiesterase inhibitors, and/or prostaglandins. The role of pulmonary vasodilator therapy in CTEPH before PTE is limited and should not delay definitive surgical therapy. Although plain deep hypothermic circulatory arrest (DHCA) is the classic technique for CTEPH, alternatives such as DHCA with antegrade cerebral perfusion are feasible as well. Prolonged mechanical ventilation after PTE remains common in part because of reperfusion pulmonary edema. Careful perioperative management can reduce the incidence of this syndrome. Because ventilator-associated pneumonia is also a common complication after PTE, it represents a major opportunity for outcome improvement, particularly because there are multiple modalities for its prevention and prompt diagnosis.

Technology Insight: recanalization with drugs and devices during acute ischemic stroke

Revascularization therapy is pivotal to saving ischemic brain from infarction. Two major randomized trials of intravenous thrombolytic therapy have established clear clinical benefit, especially for strokes caused by small-vessel occlusion. Ischemic stroke caused by large-vessel intracranial occlusion carries higher morbidity, however, and intravenous thrombolytics are less capable of opening these large vessels. This observation makes a case for delivering thrombolytics directly into the clot, or simply removing the clot mechanically. Intra-arterial thrombolytic drugs have been shown to be effective for treating middle cerebral artery occlusions in a major randomized trial. In the past 2 years, a family of mechanical thrombectomy catheters designed to remove rather than dissolve the offending clot has received FDA clearance. Such devices offer alternative therapy to patients who cannot receive thrombolytics, and can also be used in combination with thrombolytics to safely restore cerebral perfusion. Mechanical techniques have not been directly compared with intra-arterial thrombolytic strategies, but these devices might be superior to thrombolytics within vessels with particularly high clot burden, such as the carotid terminus and the basilar artery. Comprehensive stroke centers are currently available in major metropolitan areas to treat stroke via intra-arterial means, and are likely to become 'hubs' to 'spoke' hospitals that are credentialed as primary stroke centers. This design will allow any patient timely access to state-of-the-art stroke treatment tailored to their needs.