Imaging-anchored Multiomics in Cardiovascular Disease: Integrating Cardiac Imaging, Bulk, Single-cell, and Spatial Transcriptomics

Cardiovascular disease arises from interactions between inherited risk, molecular programmes, and tissue-scale remodelling that are observed clinically through imaging. Health systems now routinely generate large volumes of cardiac MRI, CT and echocardiography together with bulk, single-cell and spatial transcriptomics, yet these data are still analysed in separate pipelines. This review examines joint representations that link cardiac imaging phenotypes to transcriptomic and spatially resolved molecular states. An imaging-anchored perspective is adopted in which echocardiography, cardiac MRI and CT define a spatial phenotype of the heart, and bulk, single-cell and spatial transcriptomics provide cell-type- and location-specific molecular context. The biological and technical characteristics of these modalities are first summarised, and representation-learning strategies for each are outlined. Multimodal fusion approaches are reviewed, with emphasis on handling missing data, limited sample size, and batch effects. Finally, integrative pipelines for radiogenomics, spatial molecular alignment, and image-based prediction of gene expression are discussed, together with common failure modes, practical considerations, and open challenges. Spatial multiomics of human myocardium and atherosclerotic plaque, single-cell and spatial foundation models, and multimodal medical foundation models are collectively bringing imaging-anchored multiomics closer to large-scale cardiovascular translation.