Key result
Hemodynamic biomarkers predict risk in sICAS but lack prospective validation as treatment-effect modifiers.
Why the study?
Traditional anatomical stratification of symptomatic intracranial atherosclerotic stenosis by angiographic severity does not adequately capture the heterogeneity of ischemic mechanisms, distal hemodynamic compromise, or treatment response, prompting interest in an evidence framework for hemodynamic biomarkers.
While hemodynamic biomarkers like distal hypoperfusion and pressure ratios offer prognostic value in symptomatic intracranial atherosclerotic stenosis, none have been prospectively validated as treatment-effect modifiers to guide endovascular intervention over medical therapy.
Answers are grounded in this paper and cite their sources.
Should not yet guide sICAS intervention decisions; leaves open prospective validation of hemodynamic biomarkers as treatment-effect modifiers.
Symptomatic intracranial atherosclerotic stenosis (sICAS) has traditionally been stratified primarily according to angiographic stenosis severity. However, this anatomical approach does not adequately capture the heterogeneity of ischemic mechanisms, distal hemodynamic compromise, or treatment response, prompting increasing interest in hemodynamic biomarkers for mechanism-based risk stratification. In this review, we propose an evidence framework that evaluates these biomarkers across measurement validity, mechanistic coherence, prognostic association, treatment-effect prediction, external validation, and clinical utility, while integrating lesion function, distal perfusion, compensatory capacity, and parallel embolic and perforator pathways. Although several measures, particularly distal hypoperfusion and borderzone infarction, have shown prognostic value, the evidence identified in this review remains dominated by single-center studies, platform-specific definitions, and incompletely validated thresholds. Among the completed direct sICAS studies identified, we found no prospective validation of a hemodynamic biomarker as a treatment-effect modifier. Translation requires standardized measurement, prespecified biomarker definitions, and external validation. Claims of treatment-effect modification additionally require prespecified interaction analyses within appropriate treatment comparisons, preferably randomized. Biomarker-guided treatment selection should be supported by reliable estimates of absolute benefits and harms and evidence of clinical utility.
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Hu et al. (2026) conducted a review in Symptomatic intracranial atherosclerotic stenosis (sICAS). Hemodynamic biomarkers (pressure ratio, Angio-FF, CT-FFR, wall shear stress, Tmax delay volume, QMRA flow, collateral circulation score) was evaluated on Prognostic stratification (recurrent ischemic events) and treatment-effect modification in sICAS. Hemodynamic biomarkers such as distal hypoperfusion and borderzone infarction show prognostic value in sICAS, but no completed study has prospectively validated any as a treatment-effect modifier.
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