Patient-specific digital twins in aortic disease: integrating computational hemodynamics, immune profiling, and precision endovascular strategy

Aortic aneurysms and acute aortic syndromes continue to be significant contributors to cardiovascular morbidity and mortality; however, current risk stratification and treatment timing rely heavily on static anatomical thresholds that do not fully reflect the dynamic biology and mechanics of disease progression. Patient-specific digital twins offer a unifying paradigm where multimodal patient data are integrated into a continuously updated computational representation of an individual aorta to predict trajectories and support precise decision-making. In this review, we propose a five-domain architecture for an aortic digital twin (1): a structural-biomechanical substrate that reconstructs patient geometry and predicts wall stress and remodeling tendency; (2) computational hemodynamics to quantify flow-derived descriptors such as wall shear stress, oscillatory shear, and stagnation; (3) immunobiological integration to incorporate inflammatory activity, immune cell heterogeneity, and proteolytic remodeling signals; (4) predictive intelligence that combines multimodal features, generates individualized growth and complication predictions through uncertainty quantification, and updates predictions with longitudinal data; and (5) a sophisticated endovascular strategy layer that translates twin outputs into procedural planning, device selection, and risk-corrected surveillance. This framework highlights how the bidirectional link between inflammation and mechanics can be functionalized as a feedback ecosystem rather than a set of independent analyses, and outlines the evidence requirements for clinical translation, including validation pathways, workflow integration, and management considerations. By shifting the clinical focus from "Is the aorta large enough?" to "How will this patient's disease develop, and how can we best modify the course?", aortic digital twins can enable earlier, more individualized, and more lasting prevention of adverse aortic events.