Mapping the immune environment: spatiotemporal dynamics in cardiovascular events.

Cardiovascular disease remains a leading cause of global mortality despite advances in revascularization, pharmacotherapy, and risk stratification. Immune responses to cardiovascular damage are neither temporally linear nor spatially homogeneous; they evolve across overlapping phases and distinct anatomical compartments. Here, we propose a four-dimensional spatiotemporal framework to map immune dynamics in cardiovascular events. Temporally, responses progress from hyperacute thrombo-inflammatory activation to acute inflammation, resolution/repair, and chronic remodeling. Spatially, immune programs differentiate across the intravascular compartment, infarct/lesion core, peri-infarct border zone, distant myocardium, and device-tissue interface, each possessing distinct cellular composition, signaling pathways, and therapeutic sensitivities. By integrating molecular imaging, single-cell and spatial transcriptomics, serial biomarker profiling, and computational modeling, we demonstrate how immune activity can be resolved with increasing anatomical and temporal precision. Using neutrophil extracellular traps as a case study, we show how the same effector mechanism can exhibit different effects depending on the phase and microenvironment. Clinical trial experience with anti-inflammatory therapies further emphasizes the need to align target selection and treatment timing with the underlying immunological trajectories. A spatiotemporal approach transforms cardiovascular inflammation from a static risk factor into a measurable and potentially targetable dynamic, site-specific process. Including phase, anatomical niche, and immune phenotype in experimental design and clinical interpretation can improve precise immunomodulation and strengthen translational alignment in cardiovascular medicine.