BACKGROUND:Randomized trials have demonstrated substantial benefit of mechanical thrombectomy (MT) in selected patients treated 6-24 h after stroke onset. However, these trials relied on advanced imaging not typically available in resource-constrained settings. The RESILIENT-Extend trial aims to evaluate the efficacy and safety of MT in the 8- to 24-h window using a pragmatic imaging selection based on non-contrast computed tomography (CT) and CT angiography alone. METHODS:RESILIENT-Extend is a multicenter, randomized, controlled, open-label, blinded-endpoint, phase 3 trial conducted in Brazil. The planned sample size is 376 participants. Patients presenting with anterior-circulation large vessel occlusion within 8-24 h from time last known well will be randomized 1:1 to receive either MT plus best medical management (BMM) or BMM alone. The trial uses a minimization algorithm to balance prognostic variables including age, National Institutes of Health Stroke Scale (NIHSS), Alberta Stroke Program Early CT Score (ASPECTS), occlusion site, time window, and clinical site. The primary outcome is the distribution of 90-day modified Rankin Scale scores assessed by blinded central adjudication. DISCUSSION:RESILIENT-Extend is one of the first randomized trials to evaluate MT in the extended window using a pragmatic selection strategy based exclusively on widely available imaging modalities (non-contrast CT and CT angiography), with a focus on scalability in real-world and resource-constrained settings. TRIAL REGISTRATION:clinicaltrials.govNCT04256096.
OBJECTIVE:The objective of this study was to determine whether baseline computed tomography (CT) markers of cerebral small vessel disease (cSVD), as a surrogate of brain frailty, explain the association between age and functional outcome, potentially accounting for the reduced apparent benefit of mechanical thrombectomy (MT) in elderly patients in the RESILIENT trial. METHODS:RESILIENT was a multicenter, prospective, randomized, open-label trial with blinded outcome assessment conducted in Brazil. Patients with anterior circulation large-vessel occlusion stroke were randomized to MT plus guideline-based care or guideline-based care alone, including intravenous alteplase when eligible. A vascular neurologist blinded to clinical data evaluated baseline CT scans for cSVD markers (leukoaraiosis, lacunes, and atrophy) to derive a composite cSVD score. Multivariable logistic regression identified independent predictors of good functional outcome (modified Rankin Scale [mRS] = 0-2 at 90 days). Treatment effects were assessed across subgroups defined by age (<70 or ≥70 years) and cSVD score (0-1 vs 2-3). Mediation analysis quantified the indirect effect of age on outcome through cSVD. RESULTS:Patients with good outcomes were younger, had lower National Institutes of Health Stroke Scale (NIHSS) scores, better collaterals, lower glucose levels, lower cSVD burden, and were more frequently treated with MT. Independent predictors of good outcome included lower NIHSS, MT, lower cSVD score, and lower glucose levels. MT benefit was restricted to patients <70 years with low cSVD burden (odds ratio [OR] = 4.16, 95% confidence interval [CI] = 1.6-10.4, p < 0.01). No benefit was observed in older patients or in those with cSVD > 1. Mediation analysis showed that cSVD significantly mediated the association between age and outcome (average causal mediation effect [ACME] = -0.003, 95% CI = -0.005 to 0.00, p = 0.010). INTERPRETATION:Baseline CT markers of cSVD were independently associated with poorer outcomes and mediated the association between age and functional outcome in the RESILIENT trial, potentially explaining the lack of MT efficacy in older patients. ANN NEUROL 2026;100:361-369.
Purpose Left ventricular hypertrophy of sarcomeric and hypertensive etiology shares morphological features but differs in the underlying mechanics. We compared noninvasive myocardial work (MW) indices among nonobstructive hypertrophic cardiomyopathy (HCM), hypertensive heart disease (HHD), and controls, and assessed their diagnostic performance. Methods In this cross-sectional study, 92 individuals were stratified into HCM (n = 31), HHD (n = 31), and controls without structural heart disease (n = 30). All underwent echocardiography with analysis of global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). ROC analysis assessed functional parameters for HCM versus non-HCM and, restricted to the overlap zone, for HCM versus HHD. Results GWI and GCW were significantly lower in HCM than in HHD and controls despite preserved ejection fraction, and did not differ between HHD and controls. GWW and GWE were impaired in both pathological groups without a significant difference between them. MW correlated with markers of hypertrophy and diastolic dysfunction but not with ejection fraction. In multivariable regression, an HCM diagnosis independently predicted lower GWI and GCW, exceeding systolic pressure in magnitude. Among functional parameters, GCW showed the highest accuracy (HCM vs non-HCM: AUC 0.852; HCM vs HHD: AUC 0.799) and best reproducibility, with accuracy numerically higher than that of global longitudinal strain and significantly higher within the HCM–HHD overlap zone. Conclusion MW indices identify subclinical mechanical dysfunction with pathophysiologically distinct patterns between nonobstructive HCM and HHD. GCW was the most robust functional discriminator and may complement morphological assessment in borderline cases. Clinical trial registration Not applicable (observational study).
