Objective:

To synthesize recent discoveries in single-cell and spatial transcriptomics of cardiac myxoma, revealing that embolic propensity is an active process driven by tumor cell heterogeneity and an immunosuppressive microenvironment.

Approach:

• Molecular Mechanisms Analysis: The review analyzes the intrinsic tumor cell heterogeneity and the immunosuppressive tumor microenvironment that contribute to embolic risk, highlighting the role of a PLAT-high tumor subpopulation and dysregulated phosphodiesterase signaling.
• Clinical Integration: It discusses how molecular insights can be integrated with existing clinical models for improved embolism prediction, emphasizing the limitations of current scoring systems.
• Targeted Interventions: Proposes targeted therapies such as phosphodiesterase inhibitors and macrophage repolarization strategies to mitigate embolic risk, aiming for clinical translation.

Key Findings:

• Embolic events in cardiac myxoma are driven by tumor cell heterogeneity and an immunosuppressive microenvironment.
• A specific PLAT-high tumor subpopulation is linked to impaired cell adhesion and increased embolic risk due to dysregulated phosphodiesterase signaling.
• M2 macrophages in the tumor microenvironment promote tumor survival and contribute to embolic propensity.

Interpretation:

The findings suggest that embolism in cardiac myxoma is an active process influenced by molecular factors rather than solely mechanical characteristics.

Limitations:

• Current clinical scoring systems lack a biological basis for embolism prediction, relying on correlative clinical observations.
• The study primarily focuses on molecular mechanisms without extensive clinical validation.

Conclusion:

The review establishes a dual-paradigm of embolic pathogenesis in cardiac myxoma, integrating molecular insights with clinical applications for risk stratification and targeted therapy.