Clonal hematopoiesis of indeterminate potential (CHIP), a condition involving clonal expansion of hematopoietic stem cells with genetic variants, is associated with heart failure (HF). A study analyzing data from two large, racially diverse cohorts, the Jackson Heart Study (JHS) and Women's Health Initiative (WHI), found that TET2 CHIP was independently linked to a higher risk of HF with preserved ejection fraction (HFpEF), but not HF with reduced ejection fraction (HFrEF). The study included 8090 participants, with 512 having CHIP. TET2 CHIP was associated with a 2.35-fold increased risk of HFpEF, while DNMT3A CHIP was not significantly linked to any HF subtype. The association between CHIP and HFpEF was stronger in individuals with higher C-reactive protein (CRP) levels. The findings suggest that TET2 CHIP is a risk factor for HFpEF, potentially influencing prevention and treatment strategies. The study highlights the importance of considering CHIP in cardiovascular disease management, particularly for HFpEF. Limitations include the study's focus on specific CHIP subtypes and potential biases from WGS sensitivity. The results emphasize the need for further research into the role of CHIP in HFpEF and its underlying mechanisms.Clonal hematopoiesis of indeterminate potential (CHIP), a condition involving clonal expansion of hematopoietic stem cells with genetic variants, is associated with heart failure (HF). A study analyzing data from two large, racially diverse cohorts, the Jackson Heart Study (JHS) and Women's Health Initiative (WHI), found that TET2 CHIP was independently linked to a higher risk of HF with preserved ejection fraction (HFpEF), but not HF with reduced ejection fraction (HFrEF). The study included 8090 participants, with 512 having CHIP. TET2 CHIP was associated with a 2.35-fold increased risk of HFpEF, while DNMT3A CHIP was not significantly linked to any HF subtype. The association between CHIP and HFpEF was stronger in individuals with higher C-reactive protein (CRP) levels. The findings suggest that TET2 CHIP is a risk factor for HFpEF, potentially influencing prevention and treatment strategies. The study highlights the importance of considering CHIP in cardiovascular disease management, particularly for HFpEF. Limitations include the study's focus on specific CHIP subtypes and potential biases from WGS sensitivity. The results emphasize the need for further research into the role of CHIP in HFpEF and its underlying mechanisms.