Molecular mechanisms and targeted interventions for embolic risk in cardiac myxoma: from molecular heterogeneity to clinical translation

Cardiac myxoma (CM), the most common primary cardiac tumor, poses a significant threat to life primarily through embolic complications. While traditional risk assessment relied on clinical and morphological features, the precise molecular determinants of embolism remained poorly understood. Recent breakthroughs in single-cell and spatial transcriptomics have unveiled unprecedented insights into the cellular ecosystem of CM, revealing that embolic propensity is an active process driven by intrinsic tumor cell heterogeneity and a profoundly immunosuppressive microenvironment. This review synthesizes these recent discoveries to establish a novel paradigm: embolism arises from the confluence of a specific PLAT-high tumor subpopulation with dysregulated phosphodiesterase signaling, which impairs cell adhesion, and an M2 macrophage-dominated microenvironment that promotes tumor survival and friability. We critically analyze how these molecular mechanisms can be integrated with existing clinical models to refine embolism prediction. Furthermore, we propose a forward-looking perspective on translating these findings into targeted interventions, such as phosphodiesterase inhibitors and macrophage repolarization strategies, which hold promise as adjunctive therapies to mitigate embolic risk preoperatively and postoperatively, ultimately aiming to improve patient outcomes. This review is the first to systematically integrate the 2024 breakthroughs in single-cell and spatial transcriptomics of CM, establish a novel dual-paradigm of embolic pathogenesis coupling tumor cell intrinsic heterogeneity and immunosuppressive microenvironment crosstalk, and provide a actionable roadmap for clinical translation of molecular-guided risk stratification and targeted therapy.