Disease-associated myeloid states in cardiac remodeling: A new era of cardiac inflammation research enabled by computational biology

Adverse cardiac remodeling involves cardiomyocyte dysfunction, fibrosis, vascular alterations, and inflammation, contributing to heart failure progression. Although myeloid cells are regulators of cardiac remodeling, therapeutic strategies targeting inflammation have shown limited clinical benefit, highlighting the need for a more precise understanding of myeloid cell functions. Recent advances in single-cell transcriptomics and computational approaches have revealed substantial heterogeneity among cardiac myeloid cells and identified multiple disease-associated myeloid states with distinct molecular and functional characteristics. These findings have shifted the field beyond conventional cell classification toward understanding how specific myeloid states emerge and influence tissue remodeling through interactions with neighboring cells. In this review, we summarize recent advances in disease-associated macrophage and neutrophil states during cardiac remodeling and highlight GARP-expressing myeloid (GEM) cells as a newly identified myeloid state that promotes adverse remodeling. Understanding how disease-associated myeloid states emerge and function within multicellular tissue environments may provide new insights into cardiac remodeling.