Diagnosis by comprehensive Cardiovascular Imaging for Stroke and Transient Ischaemic Attack (D-CCIST): a randomized controlled pilot study

Accurate identification of stroke mechanism is essential to guid secondary prevention, yet conventional diagnostic pathways frequently remain incomplete or delayed. This pilot randomised controlled trial tested weather a fast-track of comprehensive cardiovascular imaging (CCI) protocol could improve diagnostic completeness and timeliness compared with routine care in acute ischaemic and transient ischaemic attack. Participants were randomised in a 1:1 ratio to CCI protocol group, which integrated ECG-gated cardiac computed tomography, extended aortic-to-vertex computed tomography angiography, and 3T brain MRI performed during a single hospital session, or to the routine diagnostic pathway delivered according to standard clinical practice. The primary outcome was the proportion of patients with incomplete diagnostic work-up (ASCO-D 9) at Day 30, defined as any unresolved aetiological category. Secondary outcomes included time to final classification, change in ASCO-D certainty, imaging utilisation, treatment modification, and new clinical events within 30 days. CCI was successfully completed in most patients and was safe, with radiation exposure within national reference limits. At Day 30, incomplete classification was markedly lower with CCI, while definite aetiological assignment nearly doubled. Diagnostic improvement was observed across the large artery, small vessel and cardioembolic domains, demonstrating that integrated multimodal imaging enhances mechanistic resolution and accelerates diagnostic completion. Analysis of secondary outcomes showed that CCI shortens the time to definitive aetiological classification and facilitated earlier alignment between diagnostic certainty and therapy choices. Mechanism-specific treatment was initiated more frequently in CCI group, whereas generic single antiplatelet use predominated in routine care. No recurrent stroke or death occurred in the CCI arm during 30-day follow-up, compared with three non-fatal events and one death under routine care. Importantly, the CCI protocol neither prolonged nor shortened hospital stay, confirmed that early comprehensive imaging can be implemented efficiently within existing inpatients pathways. Subsequent mediation analysis demonstrated that diagnostic benefits of CCI were primarily mediated through increased cardiac imaging use, rather than timing of investigation, thereby highlighting the mechanistic link between protocol design and improved diagnostic certainty. This randomised pilot study provide evidence that comprehensive cardiovascular imaging substantially improves diagnostic completeness and timeliness in acute stroke evaluation. By reducing undetermined aetiological and promoting earlier, mechanism-aligned secondary prevention without increasing length of stay, the CCI approach offers a practical, patient-centred model for bridging the diagnostic-treatment gap in secondary stroke prevention.