Is bridging therapy still required in stroke due to carotid artery terminus occlusions?

INTRODUCTION: Studies comparing endovascular stroke treatment using mechanical thrombectomy (MT) with or without prior IV tissue plasminogen activator (tPa) have included only 30% of internal carotid artery terminus occlusions (ICA-O), a known predictor of recanalization failure with IV tPa. OBJECTIVE: To carry out a retrospective multicenter analysis of prospectively collected data of consecutive patients to investigate the impact of intravenous thrombolysis on ICA-O by comparing patients treated with MT alone or bridging therapy (BT). MATERIAL AND METHODS: Patients with ICA-O treated with MT alone or BT were retrospectively examined and compared. Demographic data, vascular risk factors, treatment modalities, complications, technical and clinical outcomes were recorded. A propensity score (PS) analysis was used to compare modified Rankin Scale (mRS) score at 3 months and intracerebral hemorrhage (ICH) between groups. RESULTS: 141 consecutive patients (60% BT/40% MT) were included between January 2014 and June 2016. Baseline characteristics did not differ between the groups. There was no significant difference in the rate of Thrombolysis in Cerebral Infarction 2b/3, distal emboli, and median number of passes between the groups. There was a significant difference between BT and MT groups in the median time between imaging and groin puncture (median 97 min vs 75, p=0.007), the rate of ICH (44% vs 27%, p=0.05), but not for symptomatic ICH (18% vs 13%, p=0.49). With PS, there was a trend towards a higher rate of ICH (OR=2.3, 95% CI 0.9 to 5.9, p=0.09) in the BT group compared with the MT alone group, with no difference in mRS score ≤2 at 3 months (OR=1.6, 95% CI 0.7 to 3.7, p=0.29). CONCLUSION: There was no significant difference in clinical outcomes between patients receiving bridging therapy versus direct thrombectomy. Bridging therapy delayed time to groin puncture and increased ICH rate.

Safety and efficacy of mechanical thrombectomy in acute ischemic stroke of anticoagulated patients.

BACKGROUND: Anticoagulated patients (APs) are currently excluded from acute ischemic stroke reperfusion therapy with intravenous recombinant tissue plasminogen activator (IV-rtPA); however, these patients could benefit from mechanical thrombectomy (MT). Evidence for MT in this condition remains scarce. The aim of this study was to analyze the safety and efficacy of MT in APs. METHODS: We analyzed three patient groups from two prospective registries: APs with MT (AP-MT group), non-anticoagulated patients treated with MT (NAP-MT group), and non-anticoagulated patients treated with IV-rtPA and MT (NAP-IVTMT group). Univariate and multivariate logistic regression were used to evaluate treatment efficacy with modified Rankin Scale (mRS) ≤2 and safety (radiologic intracranial hemorrhage (rICH), symptomatic intracranial hemorrhage (sICH) and death rate at 3 months) between groups. RESULTS: 333 patients were included in the study, with 44 (12%) in the AP-MT group, 105 (31%) in the NAP-MT group, and 188 (57%) in the NAP-IVTMT group. Univariate analysis showed that the AP-MT group was older (P<0.001), more often had atrial fibrillation (P<0001), and had a higher ASPECTS (P<0.006 and P<0.002) compared with the NAP-MT group and NAP-IVTMT groups, respectively. Multivariate analysis showed that the AP-MT group had a lower risk of rICH (OR 2.77, 95% CI 1.01 to 7.61, P=0.05) but a higher risk of death at 3 months (OR 0.26, 95% CI 0.09 to 0.76, P=0.01) compared with the NAP-IVTMT group. No difference was found between the AP-MT and NAP-MT groups. CONCLUSIONS: With regard to intracranial bleeding and functional outcome at 3 months, MT in APs seems as safe and efficient as in NAPs. However, there is a higher risk of death at 3 months in the AP-MT group compared with the NAP-IVTMT group.

Search for Rare Copy-Number Variants in Congenital Heart Defects Identifies Novel Candidate Genes and a Potential Role for FOXC1 in Patients With Coarctation of the Aorta.

BACKGROUND: Congenital heart defects are the most frequent malformations among newborns and a frequent cause of morbidity and mortality. Although genetic variation contributes to congenital heart defects, their precise molecular bases remain unknown in the majority of patients. METHODS AND RESULTS: We analyzed, by high-resolution array comparative genomic hybridization, 316 children with sporadic, nonsyndromic congenital heart defects, including 76 coarctation of the aorta, 159 transposition of the great arteries, and 81 tetralogy of Fallot, as well as their unaffected parents. We identified by array comparative genomic hybridization, and validated by quantitative real-time polymerase chain reaction, 71 rare de novo (n=8) or inherited (n=63) copy-number variants (CNVs; 50 duplications and 21 deletions) in patients. We identified 113 candidate genes for congenital heart defects within these CNVs, including BTRC, CHRNB3, CSRP2BP, ERBB2, ERMARD, GLIS3, PLN, PTPRJ, RLN3, and TCTE3. No de novo CNVs were identified in patients with transposition of the great arteries in contrast to coarctation of the aorta and tetralogy of Fallot (P=0.002; Fisher exact test). A search for transcription factor binding sites showed that 93% of the rare CNVs identified in patients with coarctation of the aorta contained at least 1 gene with FOXC1-binding sites. This significant enrichment (P<0.0001; permutation test) was not observed for the CNVs identified in patients with transposition of the great arteries and tetralogy of Fallot. We hypothesize that these CNVs may alter the expression of genes regulated by FOXC1. Foxc1 belongs to the forkhead transcription factors family, which plays a critical role in cardiovascular development in mice. CONCLUSIONS: These data suggest that deregulation of FOXC1 or its downstream genes play a major role in the pathogenesis of coarctation of the aorta in humans.