Whole-Heart 3D Analysis Redefines Myocarditis

Researchers supported by the Global Autoimmune Institute published a landmark study that maps myocarditis in three dimensions for the first time. The findings offer new insight into how immune-driven heart inflammation develops and why it is often difficult to diagnose accurately.

Led by Daniela Čiháková at Johns Hopkins University, the research team used an artificial intelligence–assisted method, called CODA, to reconstruct entire mouse hearts affected by myocarditis at extremely fine detail. Rather than being distributed evenly throughout the heart, immune damage was concentrated in a small number of large, branching inflammatory areas.

These areas were most often found in the free wall of the left ventricle, a region that is rarely sampled during standard heart biopsies.

The study also uncovered distinct immune “neighborhoods” within the heart. Areas rich in T cells were more likely to appear toward the front of the heart, while regions dominated by macrophages were more common toward the back. The T cell–dense areas were closely associated with blood vessels and showed higher activity of genes involved in immune signaling and scar formation, processes that can contribute to long-term heart damage.

Importantly, similar immune patterns were seen in human hearts affected by inflammatory dilated cardiomyopathy, a serious condition that can develop after myocarditis. An accompanying editorial described the study as a major advance, helping explain why myocarditis is often missed by biopsy and highlighting how three-dimensional immune mapping could improve diagnosis, risk assessment, and future treatment strategies.

This research highlights how targeted funding can accelerate innovative approaches to understanding autoimmune and immune-mediated heart disease, bringing the field closer to more precise and personalized care.

Citations

Daoud, A., Kalinoski, H., Talor, M. V., Welsh, R. A., Jo, W., Jaime, C. M., Kolim, B., Mahto, N., Kveton, M., Weislová, I., Melenovský, V., Fabián, O., Kiemen, A. L., & Čiháková, D. (2025). Whole-heart 3D reconstruction of mouse CVB3 myocarditis reveals spatial and transcriptomic heterogeneity of immune foci. Cardiovascular research, 121(17), 2777–2790. https://doi.org/10.1093/cvr/cvaf209

Heidecker, B., & Fairweather, D. (2025). Mapping myocarditis in three dimensions. Cardiovascular research, 121(17), 2621–2623. https://doi.org/10.1093/cvr/cvaf222