Researchers have identified a promising experimental drug that could treat heart failure with preserved ejection fraction (HFpEF), the most common type of heart failure for which no therapy currently reduces mortality. In animal studies, the drug RBM20-ASO improved the heart’s ability to relax and fill with blood by increasing heart muscle flexibility. The treatment works by modulating RBM20, a key regulator of titin, a spring-like protein that controls heart muscle stiffness. The drug restored heart compliance and reduced abnormal heart thickening in mouse models of HFpEF. Importantly, researchers found that only moderate doses were needed, limiting side effects. Further safety testing in larger animal models is underway. If successful, this approach could become the first disease-modifying therapy for HFpEF, targeting the root cause of heart stiffness rather than just symptoms.

Reference:

Methawasin M, et al. Cardiovasc Res 2025;121(13):2027-2041. DOI:10.1093/cvr/cvaf171.