Clonal Hematopoiesis and Inflammatory Pathways in Heart Failure with Preserved Ejection Fraction

Purpose of Review This review aims to examine the role of clonal hematopoiesis of indeterminate potential (CHIP) in the pathophysiology of heart failure with preserved ejection fraction (HFpEF), focusing on its contribution to inflammation, disease development, and clinical implications. Recent Findings Recent studies demonstrate that CHIP is enriched in HFpEF populations and is associated with increased disease risk and worse clinical outcomes. Mechanistically, CHIP promotes inflammatory signaling through activation of pathways such as the NLRP3 inflammasome and IL-1β/IL-6 axis. TET2 mutations, in particular, have been consistently linked to diastolic dysfunction and adverse remodeling, especially in patients with high inflammatory burden and cardiometabolic comorbidities. Summary CHIP represents a novel link between ageing, inflammation, and HFpEF, contributing to disease heterogeneity and progression. It may serve as a biomarker for early detection, risk stratification, and patient phenotyping, while also offering potential therapeutic targets. Future research should focus on validating these findings and integrating CHIP into precision medicine approaches for HFpEF.