Approximately 50% of cardiac arrest survivors experience medium to long-term cognitive impairment, but no consensus currently exists regarding standardised assessment methods. Improving the understanding of underlying brain injuries pathophysiology and adopting multiplex approaches using innovative diagnostic tools offer promising avenues to improve clinical management.

To examine the pathophysiology of cerebral complications following cardiac arrest, to summarise the current state of neurological prognostication, and to explore, as a hypothesis-driven paradigm, how the biological signature of brain neurovascular unit injury, captured through a panel of emerging and innovative biomarkers, may serve as a predictive and/or diagnostic tool for cognitive impairment and overall neurological prognosis in the medium, and long term post-cardiac arrest.

The 2025 Post-Resuscitation Care Guidelines advocate a multimodal approach to early neurological prognostication within 72 h. However, no standardised strategy exists for assessing medium and long-term neurological complications in cardiac arrest survivors. Emerging research, predominantly preclinical and conducted in the field of chronic neurovascular diseases outside the cardiac arrest context, has linked brain neurovascular unit dysfunction to cognitive impairment through the expression of novel circulating biomarkers. These findings offer a potential translational research avenue applicable to cardiac arrest and represent a promising pathway to improve the understanding, diagnosis, and prognostication of delayed neurological sequelae following cardiac arrest.

Within a multimodal prognostic approach, emerging brain neurovascular unit biomarkers may provide valuable insights into the diagnosis and overall neurological prognosis in the medium and long term after cardiac arrest, thereby supporting preventive and personalised care strategies for cardiac arrest survivors.