Heterogeneity of Cardiac Regression: Implications for Biomarkers and Therapeutic Opportunities

Cardiac regression is viewed clinically as a generally beneficial consequence of pressure unloading. Here, we show that cardiac regression is not a uniform process but exhibits marked molecular heterogeneity across physiological and pathological contexts. Using multiple cardiac regression models, we identify FSTL3, a marker of Activin signaling, as a biomarker that distinguishes beneficial from maladaptive regression. We further demonstrate that persistent Activin signaling constrains functional recovery following relief of pressure overload and that pharmacological inhibition of Activin signaling enhances functional and molecular recovery after unloading.