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Background and purpose: In patients with acute ischaemic stroke (AIS), haemorrhagic transformation (HT) following endovascular treatment (EVT) is associated with poor functional outcome. However, the impact of asymptomatic HT, not linked to neurological deterioration in the acute phase, is unknown. We aimed to investigate the impact of asymptomatic PH1 (aPH1) and PH2 (aPH2) subtypes of HT on the functional outcome of patients treated with EVT. Methods: We conducted a retrospective study of patients with AIS who were consecutively admitted to our comprehensive stroke centre between January 2019 and December 2022, and who underwent EVT. We collected clinical, radiological, and procedural data. HTs were categorized according to the Heidelberg classification. The primary outcome was the shift on the modified Rankin Scale (mRS) at 3 months of follow‐up. We performed bivariate and multivariable ordinal regression analyses to test the association between aPH1/aPH2 and the primary outcome. Results: We included 314 patients (mean age = 72.5 years [SD = 13.6], 171 [54.5%] women). We detected 54 (17.2%) patients with HT; 23 (7.3%) were classified as PH2 (11 asymptomatic) and 17 (5.4%) as PH1 (16 asymptomatic). The adjusted common odds ratio for aPH2 of worsening 1 point on the 3‐month mRS was 3.32 (95% confidence interval = 1.16–9.57, p = 0.026). No association was observed for aPH1. aPH2 was also independently associated with lower odds of achieving a favourable outcome (mRS = 0–2). Neither aPH1 nor aPH2 was associated with mortality. Conclusions: In patients with AIS treated with EVT, aPH2 is independently associated with unfavourable functional outcome. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke (IS) represents a significant health burden globally, necessitating a better understanding of its genetic underpinnings to improve prevention and treatment strategies. Despite advances in IS genetics, studies focusing on the Spanish population and sex-stratified analyses are lacking., Methods: A case-control genome-wide association study was conducted with 9081 individuals (3493 IS cases and 5588 healthy controls). IS subtypes using Trial of ORG 10172 in Acute Stroke Treatment criteria were explored in a sex-stratified approach. Replication efforts involved the MEGASTROKE, GIGASTROKE, and the UK Biobank international cohorts. Post-genome-wide association study analysis included: in silico proteomic analysis, gene-based analysis, quantitative trait loci annotation, transcriptome-wide association analysis, and bioinformatic analysis using chromatin accessibility data., Results: Identified as associated with IS and its subtypes were 4 significant and independent loci. Replication confirmed 5p15.2 as a new locus associated with small-vessel occlusion stroke, with rs59970332-T as the lead variant (beta [SE], 0.13 [0.02]; P =4.34×10 -8 ). Functional analyses revealed CTNND2 given proximity and its implication in pathways involved in vascular integrity and angiogenesis. Integration of Hi-C data identified additional potentially modulated genes, and in silico proteomic analysis suggested a distinctive blood proteome profile associated with the lead variant. Gene-set enrichment analyses highlighted pathways consistent with small-vessel disease pathogenesis. Gene-based associations with known stroke-related genes such as F2 and FGG were also observed, reinforcing the relevance of our findings., Conclusions: We found CTNND2 as a potential key molecule in small-vessel occlusion stroke risk, and predominantly in males. This study sheds light on the genetic architecture of IS in the Spanish population, providing novel insights into sex-specific associations and potential molecular mechanisms. Further research, including replication in larger cohorts, is essential for a comprehensive understanding of these findings and for their translation to clinical practice., Competing Interests: Dr Arenillas reports compensation from Medtronic, Daiichi Sankyo, Boehringer Ingelheim, and Pfizer for consultant services; grants from AstraZeneca, Instituto de Salud Carlos III, European Commission and Gerencia de Salud Castilla y León; compensation from Philips for data and safety monitoring services; travel support from Daiichi Sankyo Company. Dr Ribo reports stock holdings in Methinks, Nora, and Ancaonda Biomed; compensation from Cerenovus, Vesalio, Stryker Corporation, Philips, Rapid Pulse, AptaTargets, and Medtronic MiniMed Inc for consultant services; compensation from Sensome for data and safety monitoring services. Dr Heitsch reports employment by Washington University School of Medicine in St. Louis; reports funding from National Institutes of Health and American Heart Association. Dr Dhar reports grants from National Institute of Neurological Disorders and Stroke. The other authors report no conflicts.

Introduction: In patients with acute ischemic stroke (AIS) secondary to intracranial large vessel occlusion, optimal blood pressure (BP) management following endovascular treatment (EVT) has not yet been established. The randomized trial on Hemodynamic Optimization of Cerebral Perfusion after Successful Endovascular Therapy in Patients with Acute Ischemic Stroke (HOPE) (clinicaltrials.gov id: NCT04892511) aims to demonstrate whether hemodynamic optimization using different systolic BP targets following EVT according to the degree of final recanalization, is more effective than currently recommended BP management in improving functional outcomes of patients with AIS., Methods: HOPE is an investigator-initiated multicenter clinical trial with randomized allocation, open-label treatment, and blinded endpoint evaluation (PROBE). Patients with an anterior circulation AIS within 24 h of symptom onset, treated with EVT, and showing successful recanalization (mTICI ≥2b) at the end of the procedure, are equally allocated (1:1) to hemodynamic optimization according to the study protocol versus BP management according to current guidelines (≤180/105 mm Hg). The protocol includes two different targets of systolic BP depending on the recanalization status (mTICI = 2b: 140-160 mm Hg; mTICI = 2c/3: 100-140 mm Hg). The protocol is applied within the first 72 h and includes BP lowering as well as vasopressor therapies when needed. The primary outcome is the proportion of favorable outcome (modified Rankin Scale [mRS] 0-2) at 90 days. Secondary outcomes include the shift on the mRS score, neurological deterioration, symptomatic intracerebral hemorrhage, and mortality., Conclusion: The HOPE trial will provide new information on the safety and efficacy of different BP targets following EVT according to the degree of final recanalization in patients with AIS., (© 2024 The Author(s). Published by S. Karger AG, Basel.)